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Biomaterials and Regenerative Medicine

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Materials Science".

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 110183

Special Issue Editor

Special Issue Information

Dear Colleagues,

The healthcare sector owes its evolving stature in the field of Medicine and Surgery to the advent of bioengineering and biomaterials. An increasing number of medical implants, devices, and technologies are now available due to innovative research in biomaterials and regenerative medicine.

Biomaterials and regenerative medicine are a key aspect of healthcare and witnessing accelerating market growth around the world due to an unparalleled effort in multidisciplinary research. An improved technological approach to current clinical needs has also reaped benefits, as new tailor-made solutions are being developed in partnership with chemists, physicists, engineers, biologists, physicians, and surgeons.

Diversity, translational research, and teaching are imperative for enhancing the national and international reputation, and this Special Issue will provide researchers with a platform to disseminate their data to a wider audience by bringing together researchers, academics, and clinicians from different disciplines to share their research of a multidisciplinary and translational nature. This Special Issue will act as a hub to initiate and catalyze ideas related to biomaterials and regenerative medicine.

For this Special Issue, we would like to invite papers related but not limited to the following themes:

  1. Biomaterials for soft and hard tissue repair and regeneration;
  2. Bioengineering; research in the multidisciplinary subject spectrum associated with aspects of cell biology, biochemistry, basic medical science, materials science, clinical medicine, and dentistry;
  3. Establishing a generation of biomaterials for hard and soft tissue repair and regeneration;
  4. Clinical dental material;
  5. Biocomposites;
  6. Polymers in medicine;
  7. Surface modifications for tissue engineering scaffolds;
  8. Angiogenesis/vascularization;
  9. Characterizations (chemical, physical, biological, mechanical);
  10. Spectroscopy as characterization, diagnostic, and detection tools;
  11. Biological molecules.

Prof. Dr. Ihtesham Rehman
Guest Editor

Manuscript Submission Information

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Keywords

  • Biomaterials
  • Bioengineering
  • Dental material
  • Biocomposites
  • Polymers
  • Tissue engineering scaffolds
  • Biological molecules

Published Papers (38 papers)

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15 pages, 3407 KiB  
Article
Nestin+ Mesenchymal Precursors Generate Distinct Spleen Stromal Cell Subsets and Have Immunomodulatory Function
by Jing Huang, Ronghai Deng, Weiqiang Li, Meihua Jiang, Andy Peng Xiang and Xiaoran Zhang
Int. J. Mol. Sci. 2022, 23(19), 11819; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231911819 - 05 Oct 2022
Cited by 2 | Viewed by 1698
Abstract
Mesenchymal stromal cells (MSCs) are known to be widespread in many tissues and possess a broad spectrum of immunoregulatory properties. They have been used in the treatment of a variety of inflammatory diseases; however, the therapeutic effects are still inconsistent owing to their [...] Read more.
Mesenchymal stromal cells (MSCs) are known to be widespread in many tissues and possess a broad spectrum of immunoregulatory properties. They have been used in the treatment of a variety of inflammatory diseases; however, the therapeutic effects are still inconsistent owing to their heterogeneity. Spleen stromal cells have evolved to regulate the immune response at many levels as they are bathed in a complex inflammatory milieu during infection. Therefore, it is unknown whether they have stronger immunomodulatory effects than their counterparts derived from other tissues. Here, using a transgenic mouse model expressing GFP driven by the Nestin (Nes) promoter, Nes-GFP+ cells from bone marrow and spleen were collected. Artificial lymphoid reconstruction in vivo was performed. Cell phenotype, inhibition of T cell inflammatory cytokines, and in vivo therapeutic effects were assessed. We observed Nes-GFP+ cells colocalized with splenic stromal cells and further demonstrated that these Nes-GFP+ cells had the ability to establish ectopic lymphoid-like structures in vivo. Moreover, we showed that the Nes-GFP+ cells possessed the characteristics of MSCs. Spleen-derived Nes-GFP+ cells exhibited greater immunomodulatory ability in vitro and more remarkable therapeutic efficacy in inflammatory diseases, especially inflammatory bowel disease (IBD) than bone marrow-derived Nes-GFP+ cells. Overall, our data showed that Nes-GFP+ cells contributed to subsets of spleen stromal populations and possessed the biological characteristics of MSCs with a stronger immunoregulatory function and therapeutic potential than bone marrow-derived Nes-GFP+ cells. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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25 pages, 12016 KiB  
Article
Bioactive Composite for Orbital Floor Repair and Regeneration
by Fahad AL-Hamoudi, Hamza U. Rehman, Yasir A. Almoshawah, Abdullah C. S. Talari, Aqif A. Chaudhry, Gwendolen C. Reilly and Ihtesham U. Rehman
Int. J. Mol. Sci. 2022, 23(18), 10333; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231810333 - 07 Sep 2022
Cited by 8 | Viewed by 1915
Abstract
In the maxillofacial area, specifically the orbital floor, injuries can cause bone deformities in the head and face that are difficult to repair or regenerate. Treatment methodologies include use of polymers, metal, ceramics on their own and in combinations mainly for repair purposes, [...] Read more.
In the maxillofacial area, specifically the orbital floor, injuries can cause bone deformities in the head and face that are difficult to repair or regenerate. Treatment methodologies include use of polymers, metal, ceramics on their own and in combinations mainly for repair purposes, but little attention has been paid to identify suitable materials for orbital floor regeneration. Polyurethane (PU) and hydroxyapatite (HA) micro- or nano- sized with different percentages (25%, 40% & 60%) were used to fabricate bioactive tissue engineering (TE) scaffolds using solvent casting and particulate leaching methods. Mechanical and physical characterisation of TE scaffolds was investigated by tensile tests and SEM respectively. Chemical and structural properties of PU and PU/HA scaffolds were evaluated by infrared (IR) spectroscopy and Surface properties of the bioactive scaffold were analysed using attenuated total reflectance (ATR) sampling accessory coupled with IR. Cell viability, collagen formed, VEGF protein amount and vascularisation of bioactive TE scaffold were studied. IR characterisation confirmed the integration of HA in composite scaffolds, while ATR confirmed the significant amount of HA present at the top surface of the scaffold, which was a primary objective. The SEM images confirmed the pores’ interconnectivity. Increasing the content of HA up to 40% led to an improvement in mechanical properties, and the incorporation of nano-HA was more promising than that of micro-HA. Cell viability assays (using MG63) confirmed biocompatibility and CAM assays confirmed vascularization, demonstrating that HA enhances vascularization. These properties make the resulting biomaterials very useful for orbital floor repair and regeneration. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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7 pages, 1040 KiB  
Article
The Regenerative Effects of c-Met Agonistic Antibodies in Vocal Fold Atrophy
by Hyunsu Choi, Seung-Shin Yu, Jiwon Choi and Choung-Soo Kim
Int. J. Mol. Sci. 2022, 23(14), 7818; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23147818 - 15 Jul 2022
Cited by 1 | Viewed by 1153
Abstract
Background: Atrophy of the vocal folds and the accompanying glottic insufficiency affect the quality of life. Although growth factors have been used to treat muscle atrophy, their effectiveness is limited by their short half-life. Methods: In total, 15 rabbits and 24 rats were [...] Read more.
Background: Atrophy of the vocal folds and the accompanying glottic insufficiency affect the quality of life. Although growth factors have been used to treat muscle atrophy, their effectiveness is limited by their short half-life. Methods: In total, 15 rabbits and 24 rats were used for the study. The right recurrent laryngeal nerves of all animals were transected. One month following nerve transection, PBS (PBS group), rHGF (HGF group), or a c-Met agonistic antibody (c-Met group) was injected into the paralyzed vocal folds. The larynges of the rabbits were harvested from each group for histologic examination and subjected to PCR analysis. Results: Cross-sectional areas (CSAs) of thyroarytenoid muscles were evaluated. The c-Met group had increased CSAs compared to the PBS and HGF groups, but there were no significant differences compared to normal controls. The expression levels of myogenesis-related genes were evaluated three weeks after the injection. The expression levels of myosin heavy chain IIa were significantly increased in the PBS group, while the expression levels of MyoD were increased in the c-Met group. Conclusions: The c-Met agonistic antibody showed promise for promoting muscle regeneration in a vocal fold palsy model. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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11 pages, 1783 KiB  
Article
Collagen-Based Osteogenic Nanocoating of Microrough Titanium Surfaces
by Christina Behrens, Philipp Kauffmann, Nikolaus von Hahn, Uwe Schirmer, Klaus Liefeith and Henning Schliephake
Int. J. Mol. Sci. 2022, 23(14), 7803; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23147803 - 15 Jul 2022
Cited by 2 | Viewed by 1360
Abstract
The aim of the present study was to develop a collagen/heparin-based multilayer coating on titanium surfaces for retarded release of recombinant human bone morphogenic protein 2 (rhBMP2) to enhance the osteogenic activity of implant surfaces. Polyelectrolyte multilayer (PEM) coatings were constructed on sandblasted/acid-etched [...] Read more.
The aim of the present study was to develop a collagen/heparin-based multilayer coating on titanium surfaces for retarded release of recombinant human bone morphogenic protein 2 (rhBMP2) to enhance the osteogenic activity of implant surfaces. Polyelectrolyte multilayer (PEM) coatings were constructed on sandblasted/acid-etched surfaces of titanium discs using heparin and collagen. PEM films of ten double layers were produced and overlayed with 200 µL of a rhBMP2 solution containing 15 µg rhBMP2. Subsequently, cross-linking of heparin molecules was performed using EDC/NHS chemistry to immobilize the incorporated rhBMP2. Release characteristics for 3 weeks, induction of Alkaline Phosphatase (ALP) in C2C12 cells and proliferation of human mesenchymal stem cells (hMSCs) were evaluated to analyze the osteogenic capacity of the surface. The coating incorporated 10.5 µg rhBMP2 on average per disc and did not change the surface morphology. The release profile showed a delivery of 14.5% of the incorporated growth factor during the first 24 h with a decline towards the end of the observation period with a total release of 31.3%. Cross-linking reduced the release with an almost complete suppression at 100% cross-linking. Alkaline Phosphatase was significantly increased on day 1 and day 21, indicating that the growth factor bound in the coating remains active and available after 3 weeks. Proliferation of hMSCs was significantly enhanced by the non-cross-linked PEM coating. Nanocoating using collagen/heparin-based PEMs can incorporate clinically relevant amounts of rhBMP2 on titanium surfaces with a retarded release and a sustained enhancement of osteogenic activity without changing the surface morphology. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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14 pages, 3261 KiB  
Article
Use of Self-Assembled Colloidal Prodrug Nanoparticles for Controlled Drug Delivery of Anticancer, Antifibrotic and Antibacterial Mitomycin
by Mohamed M. Abdelghafour, Ágota Deák, Diána Szabó, Imre Dékány, László Rovó and László Janovák
Int. J. Mol. Sci. 2022, 23(12), 6807; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23126807 - 18 Jun 2022
Cited by 4 | Viewed by 1818
Abstract
Herein we present the synthesis of a polymeric prodrug nanomaterial capable of spontaneous, self-assembled nanoparticle formation and of the conjugation (encapsulation) of drugs with amino and/or carboxyl and/or hydroxyl groups via ester and/or amide linkage. Mitomycin C (MMC) a versatile drug with antibiotic, [...] Read more.
Herein we present the synthesis of a polymeric prodrug nanomaterial capable of spontaneous, self-assembled nanoparticle formation and of the conjugation (encapsulation) of drugs with amino and/or carboxyl and/or hydroxyl groups via ester and/or amide linkage. Mitomycin C (MMC) a versatile drug with antibiotic, antibacterial and antineoplastic properties, was used to prove this concept. The in vitro drug release experiments showed a fast release for the pure MMC (k = 49.59 h−n); however, a significantly lower MMC dissolution rate (k = 2.25, 1.46, and 1.35 h−n) was obtained for the nanoparticles with increased cross-link density (3, 10, 21%). The successful modification and conjugation reactions were confirmed using FTIR and EDX measurements, while the mucoadhesive properties of the self-assembled particles synthesized in a simple one-pot reaction were proved by rheological measurement. The prepared biocompatible polymeric prodrugs are very promising and applicable as a drug delivery system (DDS) and useful in the area of cancer treatment. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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13 pages, 2324 KiB  
Article
Vascularization of Cell-Laden Microfibres by Femtosecond Laser Processing
by Isabel Verit, Laura Gemini, Julie Preterre, Pierre Pfirmann, Hugo Bakis, Jean-Christophe Fricain, Rainer Kling and Claire Rigothier
Int. J. Mol. Sci. 2022, 23(12), 6636; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23126636 - 14 Jun 2022
Cited by 1 | Viewed by 1292
Abstract
To face the increasing demand for organ transplantation, currently the development of tissue engineering appears as the best opportunity to effectively regenerate functional tissues and organs. However, these approaches still face the lack of an efficient method to produce an efficient vascularization system. [...] Read more.
To face the increasing demand for organ transplantation, currently the development of tissue engineering appears as the best opportunity to effectively regenerate functional tissues and organs. However, these approaches still face the lack of an efficient method to produce an efficient vascularization system. To answer these issues, the formation of an intra-volume channel within a three-dimensional, scaffold free, mature, and cell-covered collagen microfibre is here investigated through laser-induced cavitation. An intra-volume channel was formed upon irradiation with a near-infrared, femtosecond laser beam, focused with a high numerical aperture lens. The laser beam directly crossed the surface of a dense and living-cell bilayer and was focused behind the bilayer to induce channel formation in the hydrogel core while preserving the cell bilayer. Channel formation was assessed through confocal microscopy. Channel generation inside the hydrogel core was enhanced by the formation of voluminous cavitation bubbles with a lifetime longer than 30 s, which also improved intra-volume channel durability. Twenty-four hours after laser processing, cellular viability dropped due to a lack of sufficient hydration for processing longer than 10 min. However, the processing automation could drastically reduce the cellular mortality, this way enabling the formation of hollowed microfibres with a high density of living-cell outer bilayer. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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21 pages, 4288 KiB  
Article
Development and Preliminary Testing of Porcine Blood-Derived Endothelial-like Cells for Vascular Tissue Engineering Applications: Protocol Optimisation and Seeding of Decellularised Human Saphenous Veins
by Andrew Bond, Vito Bruno, Jason Johnson, Sarah George and Raimondo Ascione
Int. J. Mol. Sci. 2022, 23(12), 6633; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23126633 - 14 Jun 2022
Viewed by 1696
Abstract
Functional endothelial cells (EC) are a critical interface between blood vessels and the thrombogenic flowing blood. Disruption of this layer can lead to early thrombosis, inflammation, vessel restenosis, and, following coronary (CABG) or peripheral (PABG) artery bypass graft surgery, vein graft failure. Blood-derived [...] Read more.
Functional endothelial cells (EC) are a critical interface between blood vessels and the thrombogenic flowing blood. Disruption of this layer can lead to early thrombosis, inflammation, vessel restenosis, and, following coronary (CABG) or peripheral (PABG) artery bypass graft surgery, vein graft failure. Blood-derived ECs have shown potential for vascular tissue engineering applications. Here, we show the development and preliminary testing of a method for deriving porcine endothelial-like cells from blood obtained under clinical conditions for use in translational research. The derived cells show cobblestone morphology and expression of EC markers, similar to those seen in isolated porcine aortic ECs (PAEC), and when exposed to increasing shear stress, they remain viable and show mRNA expression of EC markers similar to PAEC. In addition, we confirm the feasibility of seeding endothelial-like cells onto a decellularised human vein scaffold with approximately 90% lumen coverage at lower passages, and show that increasing cell passage results in reduced endothelial coverage. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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21 pages, 7876 KiB  
Article
Suitability of Chitosan Scaffolds with Carbon Nanotubes for Bone Defects Treated with Photobiomodulation
by Samantha Ketelyn Silva, Ana Maria Guzzi Plepis, Virginia da Conceição Amaro Martins, Marilia Marta Horn, Daniela Vieira Buchaim, Rogerio Leone Buchaim, André Antônio Pelegrine, Vinícius Rodrigues Silva, Mateus Hissashi Matsumoto Kudo, José Francisco Rebello Fernandes, Fabricio Montenegro Nazari and Marcelo Rodrigues da Cunha
Int. J. Mol. Sci. 2022, 23(12), 6503; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23126503 - 10 Jun 2022
Cited by 9 | Viewed by 1946
Abstract
Biomaterials have been investigated as an alternative for the treatment of bone defects, such as chitosan/carbon nanotubes scaffolds, which allow cell proliferation. However, bone regeneration can be accelerated by electrotherapeutic resources that act on bone metabolism, such as low-level laser therapy (LLLT). Thus, [...] Read more.
Biomaterials have been investigated as an alternative for the treatment of bone defects, such as chitosan/carbon nanotubes scaffolds, which allow cell proliferation. However, bone regeneration can be accelerated by electrotherapeutic resources that act on bone metabolism, such as low-level laser therapy (LLLT). Thus, this study evaluated the regeneration of bone lesions grafted with chitosan/carbon nanotubes scaffolds and associated with LLLT. For this, a defect (3 mm) was created in the femur of thirty rats, which were divided into 6 groups: Control (G1/Control), LLLT (G2/Laser), Chitosan/Carbon Nanotubes (G3/C+CNTs), Chitosan/Carbon Nanotubes with LLLT (G4/C+CNTs+L), Mineralized Chitosan/Carbon Nanotubes (G5/C+CNTsM) and Mineralized Chitosan/Carbon Nanotubes with LLLT (G6/C+CNTsM+L). After 5 weeks, the biocompatibility of the chitosan/carbon nanotubes scaffolds was observed, with the absence of inflammatory infiltrates and fibrotic tissue. Bone neoformation was denser, thicker and voluminous in G6/C+CNTsM+L. Histomorphometric analyses showed that the relative percentage and standard deviations (mean ± SD) of new bone formation in groups G1 to G6 were 59.93 ± 3.04a (G1/Control), 70.83 ± 1.21b (G2/Laser), 70.09 ± 4.31b (G3/C+CNTs), 81.6 ± 5.74c (G4/C+CNTs+L), 81.4 ± 4.57c (G5/C+CNTsM) and 91.3 ± 4.81d (G6/C+CNTsM+L), respectively, with G6 showing a significant difference in relation to the other groups (a ≠ b ≠ c ≠ d; p < 0.05). Immunohistochemistry also revealed good expression of osteocalcin (OC), osteopontin (OP) and vascular endothelial growth factor (VEGF). It was concluded that chitosan-based carbon nanotube materials combined with LLLT effectively stimulated the bone healing process. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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17 pages, 3823 KiB  
Article
Hydroxyapatite-Integrated, Heparin- and Glycerol-Functionalized Chitosan-Based Injectable Hydrogels with Improved Mechanical and Proangiogenic Performance
by Fatma Z. Kocak, Muhammad Yar and Ihtesham U. Rehman
Int. J. Mol. Sci. 2022, 23(10), 5370; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23105370 - 11 May 2022
Cited by 23 | Viewed by 2543
Abstract
The investigation of natural bioactive injectable composites to induce angiogenesis during bone regeneration has been a part of recent minimally invasive regenerative medicine strategies. Our previous study involved the development of in situ-forming injectable composite hydrogels (Chitosan/Hydroxyapatite/Heparin) for bone regeneration. These hydrogels offered [...] Read more.
The investigation of natural bioactive injectable composites to induce angiogenesis during bone regeneration has been a part of recent minimally invasive regenerative medicine strategies. Our previous study involved the development of in situ-forming injectable composite hydrogels (Chitosan/Hydroxyapatite/Heparin) for bone regeneration. These hydrogels offered facile rheology, injectability, and gelation at 37 °C, as well as promising pro-angiogenic abilities. In the current study, these hydrogels were modified using glycerol as an additive and a pre-sterile production strategy to enhance their mechanical strength. These modifications allowed a further pH increment during neutralisation with maintained solution homogeneity. The synergetic effect of the pH increment and further hydrogen bonding due to the added glycerol improved the strength of the hydrogels substantially. SEM analyses showed highly cross-linked hydrogels (from high-pH solutions) with a hierarchical interlocking pore morphology. Hydrogel solutions showed more elastic flow properties and incipient gelation times decreased to just 2 to 3 min at 37 °C. Toluidine blue assay and SEM analyses showed that heparin formed a coating at the top layer of the hydrogels which contributed anionic bioactive surface features. The chick chorioallantoic membrane (CAM) assay confirmed significant enhancement of angiogenesis with chitosan-matrixed hydrogels comprising hydroxyapatite and small quantities of heparin (33 µg/mL) compared to basic chitosan hydrogels. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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20 pages, 5070 KiB  
Article
Novel Antibacterial Copolymers Based on Quaternary Ammonium Urethane-Dimethacrylate Analogues and Triethylene Glycol Dimethacrylate
by Marta W. Chrószcz, Izabela M. Barszczewska-Rybarek and Alicja Kazek-Kęsik
Int. J. Mol. Sci. 2022, 23(9), 4954; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23094954 - 29 Apr 2022
Cited by 12 | Viewed by 1596
Abstract
The growing scale of secondary caries and occurrence of antibiotic-resistant bacterial strains require the development of antibacterial dental composites. It can be achieved by the chemical introduction of quaternary ammonium dimethacrylates into dental composites. In this study, physicochemical and antibacterial properties of six [...] Read more.
The growing scale of secondary caries and occurrence of antibiotic-resistant bacterial strains require the development of antibacterial dental composites. It can be achieved by the chemical introduction of quaternary ammonium dimethacrylates into dental composites. In this study, physicochemical and antibacterial properties of six novel copolymers consisting of 60 wt. % quaternary ammonium urethane-dimethacrylate analogues (QAUDMA) and 40 wt. % triethylene glycol dimethacrylate (TEGDMA) were investigated. Uncured compositions had suitable refractive index (RI), density (dm), and glass transition temperature (Tgm). Copolymers had low polymerization shrinkage (S), high degree of conversion (DC) and high glass transition temperature (Tgp). They also showed high antibacterial effectiveness against S. aureus and E. coli bacterial strains. It was manifested by the reduction in cell proliferation, decrease in the number of bacteria adhered on their surfaces, and presence of growth inhibition zones. It can be concluded that the copolymerization of bioactive QAUDMAs with TEGDMA provided copolymers with high antibacterial activity and rewarding physicochemical properties. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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27 pages, 10058 KiB  
Article
Scaffold Pore Curvature Influences ΜSC Fate through Differential Cellular Organization and YAP/TAZ Activity
by W. Benton Swanson, Maiko Omi, Seth M. Woodbury, Lindsey M. Douglas, Miranda Eberle, Peter X. Ma, Nan E. Hatch and Yuji Mishina
Int. J. Mol. Sci. 2022, 23(9), 4499; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23094499 - 19 Apr 2022
Cited by 20 | Viewed by 2734
Abstract
Tissue engineering aims to repair, restore, and/or replace tissues in the human body as an alternative to grafts and prostheses. Biomaterial scaffolds can be utilized to provide a three-dimensional microenvironment to facilitate tissue regeneration. Previously, we reported that scaffold pore size influences vascularization [...] Read more.
Tissue engineering aims to repair, restore, and/or replace tissues in the human body as an alternative to grafts and prostheses. Biomaterial scaffolds can be utilized to provide a three-dimensional microenvironment to facilitate tissue regeneration. Previously, we reported that scaffold pore size influences vascularization and extracellular matrix composition both in vivo and in vitro, to ultimately influence tissue phenotype for regenerating cranial suture and bone tissues, which have markedly different tissue properties despite similar multipotent stem cell populations. To rationally design biomaterials for specific cell and tissue fate specification, it is critical to understand the molecular processes governed by cell-biomaterial interactions, which guide cell fate specification. Building on our previous work, in this report we investigated the hypothesis that scaffold pore curvature, the direct consequence of pore size, modulates the differentiation trajectory of mesenchymal stem cells (MSCs) through alterations in the cytoskeleton. First, we demonstrated that sufficiently small pores facilitate cell clustering in subcutaneous explants cultured in vivo, which we previously reported to demonstrate stem tissue phenotype both in vivo and in vitro. Based on this observation, we cultured cell-scaffold constructs in vitro to assess early time point interactions between cells and the matrix as a function of pore size. We demonstrate that principle curvature directly influences nuclear aspect and cell aggregation in vitro. Scaffold pores with a sufficiently low degree of principle curvature enables cell differentiation; pharmacologic inhibition of actin cytoskeleton polymerization in these scaffolds decreased differentiation, indicating a critical role of the cytoskeleton in transducing cues from the scaffold pore microenvironment to the cell nucleus. We fabricated a macropore model, which allows for three-dimensional confocal imaging and demonstrates that a higher principle curvature facilitates cell aggregation and the formation of a potentially protective niche within scaffold macropores which prevents MSC differentiation and retains their stemness. Sufficiently high principle curvature upregulates yes-associated protein (YAP) phosphorylation while decreased principle curvature downregulates YAP phosphorylation and increases YAP nuclear translocation with subsequent transcriptional activation towards an osteogenic differentiation fate. Finally, we demonstrate that the inhibition of the YAP/TAZ pathway causes a defect in differentiation, while YAP/TAZ activation causes premature differentiation in a curvature-dependent way when modulated by verteporfin (VP) and 1-oleyl-lysophosphatidic acid (LPA), respectively, confirming the critical role of biomaterials-mediated YAP/TAZ signaling in cell differentiation and fate specification. Our data support that the principle curvature of scaffold macropores is a critical design criterion which guides the differentiation trajectory of mesenchymal stem cells’ scaffolds. Biomaterial-mediated regulation of YAP/TAZ may significantly contribute to influencing the regenerative outcomes of biomaterials-based tissue engineering strategies through their specific pore design. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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17 pages, 4258 KiB  
Article
Preparation and Characterization of Plasma-Derived Fibrin Hydrogels Modified by Alginate di-Aldehyde
by Raúl Sanz-Horta, Ana Matesanz, José Luis Jorcano, Diego Velasco, Pablo Acedo, Alberto Gallardo, Helmut Reinecke and Carlos Elvira
Int. J. Mol. Sci. 2022, 23(8), 4296; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23084296 - 13 Apr 2022
Cited by 9 | Viewed by 2389
Abstract
Fibrin hydrogels are one of the most popular scaffolds used in tissue engineering due to their excellent biological properties. Special attention should be paid to the use of human plasma-derived fibrin hydrogels as a 3D scaffold in the production of autologous skin grafts, [...] Read more.
Fibrin hydrogels are one of the most popular scaffolds used in tissue engineering due to their excellent biological properties. Special attention should be paid to the use of human plasma-derived fibrin hydrogels as a 3D scaffold in the production of autologous skin grafts, skeletal muscle regeneration and bone tissue repair. However, mechanical weakness and rapid degradation, which causes plasma-derived fibrin matrices to shrink significantly, prompted us to improve their stability. In our study, plasma-derived fibrin was chemically bonded to oxidized alginate (alginate di-aldehyde, ADA) at 10%, 20%, 50% and 80% oxidation, by Schiff base formation, to produce natural hydrogels for tissue engineering applications. First, gelling time studies showed that the degree of ADA oxidation inhibits fibrin polymerization, which we associate with fiber increment and decreased fiber density; moreover, the storage modulus increased when increasing the final volume of CaCl2 (1% w/v) from 80 µL to 200 µL per milliliter of hydrogel. The contraction was similar in matrices with and without human primary fibroblasts (hFBs). In addition, proliferation studies with encapsulated hFBs showed an increment in cell viability in hydrogels with ADA at 10% oxidation at days 1 and 3 with 80 µL of CaCl2; by increasing this compound (CaCl2), the proliferation does not significantly increase until day 7. In the presence of 10% alginate oxidation, the proliferation results are similar to the control, in contrast to the sample with 20% oxidation whose proliferation decreases. Finally, the viability studies showed that the hFB morphology was maintained regardless of the degree of oxidation used; however, the quantity of CaCl2 influences the spread of the hFBs. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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17 pages, 3281 KiB  
Article
Silkworm Gut Fibres from Silk Glands of Samia cynthia ricini—Potential Use as a Scaffold in Tissue Engineering
by Salvador D. Aznar-Cervantes, Ana Pagán, María J. Candel, José Pérez-Rigueiro and José L. Cenis
Int. J. Mol. Sci. 2022, 23(7), 3888; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23073888 - 31 Mar 2022
Cited by 3 | Viewed by 1996
Abstract
High-performance fibroin fibres are ideal candidates for the manufacture of scaffolds with applications in tissue engineering due to the excellent mechanical properties and optimal biocompatibility of this protein. In this work, the manufacture of high-strength fibres made from the silk glands of Samia [...] Read more.
High-performance fibroin fibres are ideal candidates for the manufacture of scaffolds with applications in tissue engineering due to the excellent mechanical properties and optimal biocompatibility of this protein. In this work, the manufacture of high-strength fibres made from the silk glands of Samia cynthia ricini is explored. The glands were subjected to soaking in aqueous dissolutions of acetic acid and stretched to manufacture the fibres. The materials produced were widely characterized, in terms of morphology, mechanical properties, crystallinity and content of secondary structures, comparing them with those produced by the standard procedure published for Bombyx mori. In addition, mechanical properties and biocompatibility of a braided scaffold produced from these fibres was evaluated. The results obtained show that the fibres from B. mori present a higher degree of crystallinity than those from S. c. ricini, which is reflected in higher values of elastic modulus and lower values of strain at break. Moreover, a decrease in the elongation values of the fibres from S. c. ricini was observed as the concentration of acetic acid was increased during the manufacture. On the other hand, the study of the braided scaffolds showed higher values of tensile strength and strain at break in the case of S. c. ricini materials and similar values of elastic modulus, compared to those of B. mori, displaying both scaffolds optimal biocompatibility using a fibroblast cell line. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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21 pages, 7612 KiB  
Article
Identification, Isolation, and Characterization of Melanocyte Precursor Cells in the Human Limbal Stroma
by Shen Li, Matthias Zenkel, Friedrich E. Kruse, Andreas Gießl and Ursula Schlötzer-Schrehardt
Int. J. Mol. Sci. 2022, 23(7), 3756; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23073756 - 29 Mar 2022
Cited by 4 | Viewed by 2939
Abstract
Given their vital role in the homeostasis of the limbal stem cell niche, limbal melanocytes have emerged as promising candidates for tissue engineering applications. This study aimed to isolate and characterize a population of melanocyte precursors in the limbal stroma, compared with melanocytes [...] Read more.
Given their vital role in the homeostasis of the limbal stem cell niche, limbal melanocytes have emerged as promising candidates for tissue engineering applications. This study aimed to isolate and characterize a population of melanocyte precursors in the limbal stroma, compared with melanocytes originating from the limbal epithelium, using magnetic-activated cell sorting (MACS) with positive (CD117/c-Kit microbeads) or negative (CD326/EpCAM or anti-fibroblast microbeads) selection approaches. Both approaches enabled fast and easy isolation and cultivation of pure limbal epithelial and stromal melanocyte populations, which differed in phenotype and gene expression, but exhibited similar functional properties regarding proliferative potential, pigmentation, and support of clonal growth of limbal epithelial stem/progenitor cells (LEPCs). In both melanocyte populations, limbus-specific matrix (laminin 511-E8) and soluble factors (LEPC-derived conditioned medium) stimulated melanocyte adhesion, dendrite formation, melanogenesis, and expression of genes involved in UV protection and immune regulation. The findings provided not only a novel protocol for the enrichment of pure melanocyte populations from limbal tissue applying easy-to-use MACS technology, but also identified a population of stromal melanocyte precursors, which may serve as a reservoir for the replacement of damaged epithelial melanocytes and an alternative resource for tissue engineering applications. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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14 pages, 2049 KiB  
Article
Comparison of Injectable Biphasic Calcium Phosphate and a Bovine Xenograft in Socket Preservation: Qualitative and Quantitative Histologic Study in Humans
by Marija Čandrlić, Matej Tomas, Matej Karl, Lucija Malešić, Aleksandar Včev, Željka Perić Kačarević and Marko Matijević
Int. J. Mol. Sci. 2022, 23(5), 2539; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23052539 - 25 Feb 2022
Cited by 10 | Viewed by 2189
Abstract
This study is the first histologic evaluation of an injectable biphasic calcium phosphate (IBCP) in humans six months after socket preservation according to the principles of guided bone regeneration. After tooth extraction, the alveolar ridge of 21 patients was augmented with IBCP (maxresorb [...] Read more.
This study is the first histologic evaluation of an injectable biphasic calcium phosphate (IBCP) in humans six months after socket preservation according to the principles of guided bone regeneration. After tooth extraction, the alveolar ridge of 21 patients was augmented with IBCP (maxresorb® inject) in the test group, while 20 patients in the control group received a bovine xenograft (BX) (cerabone®). Six months after augmentation, a reentry procedure was performed to collect biopsies of regenerated bone for qualitative and quantitative histologic analysis. A total of 20 biopsies were taken for analysis. Qualitative histologic analysis showed complete integration of the biomaterial and no inflammatory tissue reaction, indicating the biocompatibility of the bone grafts and the surrounding tissue in both groups. Histomorphometric analysis showed comparable results in terms of newly formed bone (IBCP: 26.47 ± 14.71%, BX: 30.47 ± 16.39%) and residual biomaterial (IBCP: 13.1 ± 14.07%, BX: 17.89 ± 11.81%), with no significant difference found across groups (p > 0.05, Mann—Whitney U test). Statistical significance between groups was found in the result of soft tissue percentage (IBCP: 60.43 ± 12.73%, BX: 51.64 ± 14.63%, p = 0.046, Mann—Whitney U test). To conclude, IBCP and BX showed good osteoconductivity and biocompatibility with comparable new bone formation six months after alveolar ridge preservation. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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15 pages, 5837 KiB  
Article
Modification of TiAlV Alloys with Hybrid Layers Containing Metallic Nanoparticles Obtained by the Sol–Gel Method: Surface and Structural Properties
by Magdalena Ziąbka, Katarzyna Matysiak, Katarzyna Walczak, Marcin Gajek and Katarzyna Cholewa-Kowalska
Int. J. Mol. Sci. 2022, 23(4), 2283; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23042283 - 18 Feb 2022
Cited by 3 | Viewed by 1572
Abstract
The aim of the work was to obtain hybrid coatings containing silver, copper, and zinc nanoparticles on the TiAlV medical alloy via a sol–gel process. The developed layers were designed to bring about a bactericidal and fungicidal effect, as well as for protection [...] Read more.
The aim of the work was to obtain hybrid coatings containing silver, copper, and zinc nanoparticles on the TiAlV medical alloy via a sol–gel process. The developed layers were designed to bring about a bactericidal and fungicidal effect, as well as for protection against surgical scratches during the implantation of implants used in veterinary medicine. In this work, the authors focused on evaluating the microstructure (SEM + EDS); the structure (XRD, FTIR); and the surface properties, such as wettability, free surface energy, and roughness of layers with various concentrations of metallic nanoparticles (2 and 5 mol %). Our results confirmed that the sol–gel method enables the easy manufacturing of hybrid layers endowed with different porosity values as well as various shapes and sizes of metallic nanoparticles. A higher concentration of nanoparticles was observed on the surface containing 5 mol % of metallic salts. The highest degree of homogeneity was obtained for the layers containing silver nanoparticles. In addition, the silver nanoparticles were round and had the smallest dimensions, even below 20 nm. The FTIR and XRD structural studies confirmed the presence of an organosilicon matrix containing all three types of the metallic particles. We conclude that the higher concentration of nanoparticles influenced the alloy surface parameters. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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13 pages, 4474 KiB  
Article
Enhanced BMP-2-Mediated Bone Repair Using an Anisotropic Silk Fibroin Scaffold Coated with Bone-like Apatite
by Christian Deininger, Andrea Wagner, Patrick Heimel, Elias Salzer, Xavier Monforte Vila, Nadja Weißenbacher, Johannes Grillari, Heinz Redl, Florian Wichlas, Thomas Freude, Herbert Tempfer, Andreas Herbert Teuschl-Woller and Andreas Traweger
Int. J. Mol. Sci. 2022, 23(1), 283; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23010283 - 28 Dec 2021
Cited by 7 | Viewed by 2693
Abstract
The repair of large bone defects remains challenging and often requires graft material due to limited availability of autologous bone. In clinical settings, collagen sponges loaded with excessive amounts of bone morphogenetic protein 2 (rhBMP-2) are occasionally used for the treatment of bone [...] Read more.
The repair of large bone defects remains challenging and often requires graft material due to limited availability of autologous bone. In clinical settings, collagen sponges loaded with excessive amounts of bone morphogenetic protein 2 (rhBMP-2) are occasionally used for the treatment of bone non-unions, increasing the risk of adverse events. Therefore, strategies to reduce rhBMP-2 dosage are desirable. Silk scaffolds show great promise due to their favorable biocompatibility and their utility for various biofabrication methods. For this study, we generated silk scaffolds with axially aligned pores, which were subsequently treated with 10× simulated body fluid (SBF) to generate an apatitic calcium phosphate coating. Using a rat femoral critical sized defect model (CSD) we evaluated if the resulting scaffold allows the reduction of BMP-2 dosage to promote efficient bone repair by providing appropriate guidance cues. Highly porous, anisotropic silk scaffolds were produced, demonstrating good cytocompatibility in vitro and treatment with 10× SBF resulted in efficient surface coating. In vivo, the coated silk scaffolds loaded with a low dose of rhBMP-2 demonstrated significantly improved bone regeneration when compared to the unmineralized scaffold. Overall, our findings show that this simple and cost-efficient technique yields scaffolds that enhance rhBMP-2 mediated bone healing. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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15 pages, 9882 KiB  
Article
Tailoring Silicon Nitride Surface Chemistry for Facilitating Odontogenic Differentiation of Rat Dental Pulp Cells
by Yanan Gong, Yoshitomo Honda, Tetsuya Adachi, Elia Marin, Kazushi Yoshikawa, Giuseppe Pezzotti and Kazuyo Yamamoto
Int. J. Mol. Sci. 2021, 22(23), 13130; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222313130 - 04 Dec 2021
Cited by 4 | Viewed by 1751
Abstract
Silicon nitride (Si3N4) can facilitate bone formation; hence, it is used as a biomaterial in orthopedics. Nevertheless, its usability for dentistry is unexplored. The aim of the present study was to investigate the effect of Si3N4 [...] Read more.
Silicon nitride (Si3N4) can facilitate bone formation; hence, it is used as a biomaterial in orthopedics. Nevertheless, its usability for dentistry is unexplored. The aim of the present study was to investigate the effect of Si3N4 granules for the proliferation and odontogenic differentiation of rat dental pulp cells (rDPCs). Four different types of Si3N4 granules were prepared, which underwent different treatments to form pristine as-synthesized Si3N4, chemically treated Si3N4, thermally treated Si3N4, and Si3N4 sintered with 3 wt.% yttrium oxide (Y2O3). rDPCs were cultured on or around the Si3N4 granular beds. Compared with the other three types of Si3N4 granules, the sintered Si3N4 granules significantly promoted cellular attachment, upregulated the expression of odontogenic marker genes (Dentin Matrix Acidic Phosphoprotein 1 and Dentin Sialophosphoprotein) in the early phase, and enhanced the formation of mineralization nodules. Furthermore, the water contact angle of sintered Si3N4 was also greatly increased to 40°. These results suggest that the sintering process for Si3N4 with Y2O3 positively altered the surface properties of pristine as-synthesized Si3N4 granules, thereby facilitating the odontogenic differentiation of rDPCs. Thus, the introduction of a sintering treatment for Si3N4 granules is likely to facilitate their use in the clinical application of dentistry. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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15 pages, 8769 KiB  
Article
Influence of Culture Period on Osteoblast Differentiation of Tissue-Engineered Bone Constructed by Apatite-Fiber Scaffolds Using Radial-Flow Bioreactor
by Kitaru Suzuki, Jun Fukasawa, Maiko Miura, Poon Nian Lim, Michiyo Honda, Tomokazu Matsuura and Mamoru Aizawa
Int. J. Mol. Sci. 2021, 22(23), 13080; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222313080 - 03 Dec 2021
Cited by 4 | Viewed by 1510
Abstract
With the limitation of autografts, the development of alternative treatments for bone diseases to alleviate autograft-related complications is highly demanded. In this study, a tissue-engineered bone was formed by culturing rat bone marrow cells (RBMCs) onto porous apatite-fiber scaffolds (AFSs) with three-dimensional (3D) [...] Read more.
With the limitation of autografts, the development of alternative treatments for bone diseases to alleviate autograft-related complications is highly demanded. In this study, a tissue-engineered bone was formed by culturing rat bone marrow cells (RBMCs) onto porous apatite-fiber scaffolds (AFSs) with three-dimensional (3D) interconnected pores using a radial-flow bioreactor (RFB). Using the optimized flow rate, the effect of different culturing periods on the development of tissue-engineered bone was investigated. The 3D cell culture using RFB was performed for 0, 1 or 2 weeks in a standard medium followed by 0, 1 or 2 weeks in a differentiation medium. Osteoblast differentiation in the tissue-engineered bone was examined by alkaline phosphatase (ALP) and osteocalcin (OC) assays. Furthermore, the tissue-engineered bone was histologically examined by hematoxylin and eosin and alizarin red S stains. We found that the ALP activity and OC content of calcified cells tended to increase with the culture period, and the differentiation of tissue-engineered bone could be controlled by varying the culture period. In addition, the employment of RFB and AFSs provided a favorable 3D environment for cell growth and differentiation. Overall, these results provide valuable insights into the design of tissue-engineered bone for clinical applications. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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22 pages, 3669 KiB  
Article
Contribution of the Transcription Factors Sp1/Sp3 and AP-1 to Clusterin Gene Expression during Corneal Wound Healing of Tissue-Engineered Human Corneas
by Christelle Gross, Gaëtan Le-Bel, Pascale Desjardins, Manel Benhassine, Lucie Germain and Sylvain L. Guérin
Int. J. Mol. Sci. 2021, 22(22), 12426; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222212426 - 17 Nov 2021
Cited by 5 | Viewed by 1934
Abstract
In order to reduce the need for donor corneas, understanding of corneal wound healing and development of an entirely tissue-engineered human cornea (hTECs) is of prime importance. In this study, we exploited the hTEC to determine how deep wound healing affects the transcriptional [...] Read more.
In order to reduce the need for donor corneas, understanding of corneal wound healing and development of an entirely tissue-engineered human cornea (hTECs) is of prime importance. In this study, we exploited the hTEC to determine how deep wound healing affects the transcriptional pattern of corneal epithelial cells through microarray analyses. We demonstrated that the gene encoding clusterin (CLU) has its expression dramatically repressed during closure of hTEC wounds. Western blot analyses confirmed a strong reduction in the expression of the clusterin isoforms after corneal damage and suggest that repression of CLU gene expression might be a prerequisite to hTEC wound closure. Transfection with segments from the human CLU gene promoter revealed the presence of three regulatory regions: a basal promoter and two more distal negative regulatory regions. The basal promoter bears DNA binding sites for very potent transcription factors (TFs): Activator Protein-1 (AP-1) and Specificity protein-1 and 3 (Sp1/Sp3). By exploiting electrophoretic mobility shift assays (EMSA), we demonstrated that AP-1 and Sp1/Sp3 have their DNA binding site overlapping with one another in the basal promoter of the CLU gene in hCECs. Interestingly, expression of both these TFs is reduced (at the protein level) during hTEC wound healing, thereby contributing to the extinction of CLU gene expression during that process. The results of this study contribute to a better understanding of the molecular mechanisms accounting for the repression of CLU gene expression during corneal wound healing. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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10 pages, 9396 KiB  
Article
Comparing the Osteogenic Potential and Bone Regeneration Capacities of Dedifferentiated Fat Cells and Adipose-Derived Stem Cells In Vitro and In Vivo: Application of DFAT Cells Isolated by a Mesh Method
by Kiyofumi Takabatake, Masakazu Matsubara, Eiki Yamachika, Yuki Fujita, Yuki Arimura, Kazuki Nakatsuji, Keisuke Nakano, Histoshi Nagatsuka and Seiji Iida
Int. J. Mol. Sci. 2021, 22(22), 12392; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222212392 - 17 Nov 2021
Cited by 2 | Viewed by 2356
Abstract
Background: We investigated and compared the osteogenic potential and bone regeneration capacities of dedifferentiated fat cells (DFAT cells) and adipose-derived stem cells (ASCs). Method: We isolated DFAT cells and ASCs from GFP mice. DFAT cells were established by a new culture method using [...] Read more.
Background: We investigated and compared the osteogenic potential and bone regeneration capacities of dedifferentiated fat cells (DFAT cells) and adipose-derived stem cells (ASCs). Method: We isolated DFAT cells and ASCs from GFP mice. DFAT cells were established by a new culture method using a mesh culture instead of a ceiling culture. The isolated DFAT cells and ASCs were incubated in osteogenic medium, then alizarin red staining, alkaline phosphatase (ALP) assays, and RT-PCR (for RUNX2, osteopontin, DLX5, osterix, and osteocalcin) were performed to evaluate the osteoblastic differentiation ability of both cell types in vitro. In vivo, the DFAT cells and ASCs were incubated in osteogenic medium for four weeks and seeded on collagen composite scaffolds, then implanted subcutaneously into the backs of mice. We then performed hematoxylin and eosin staining and immunostaining for GFP and osteocalcin. Results: The alizarin red-stained areas in DFAT cells showed weak calcification ability at two weeks, but high calcification ability at three weeks, similar to ASCs. The ALP levels of ASCs increased earlier than in DFAT cells and showed a significant difference (p < 0.05) at 6 and 9 days. The ALP levels of DFATs were higher than those of ASCs after 12 days. The expression levels of osteoblast marker genes (osterix and osteocalcin) of DFAT cells and ASCs were higher after osteogenic differentiation culture. Conclusion: DFAT cells are easily isolated from a small amount of adipose tissue and are readily expanded with high purity; thus, DFAT cells are applicable to many tissue-engineering strategies and cell-based therapies. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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25 pages, 23986 KiB  
Article
Complexation of CXCL12, FGF-2 and VEGF with Heparin Modulates the Protein Release from Alginate Microbeads
by Edyta Adrian, Dušana Treľová, Elena Filová, Marta Kumorek, Volodymyr Lobaz, Rafal Poreba, Olga Janoušková, Ognen Pop-Georgievski, Igor Lacík and Dana Kubies
Int. J. Mol. Sci. 2021, 22(21), 11666; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111666 - 28 Oct 2021
Cited by 5 | Viewed by 2782
Abstract
Long-term delivery of growth factors and immunomodulatory agents is highly required to support the integrity of tissue in engineering constructs, e.g., formation of vasculature, and to minimize immune response in a recipient. However, for proteins with a net positive charge at the physiological [...] Read more.
Long-term delivery of growth factors and immunomodulatory agents is highly required to support the integrity of tissue in engineering constructs, e.g., formation of vasculature, and to minimize immune response in a recipient. However, for proteins with a net positive charge at the physiological pH, controlled delivery from negatively charged alginate (Alg) platforms is challenging due to electrostatic interactions that can hamper the protein release. In order to regulate such interactions between proteins and the Alg matrix, we propose to complex proteins of interest in this study - CXCL12, FGF-2, VEGF - with polyanionic heparin prior to their encapsulation into Alg microbeads of high content of α-L-guluronic acid units (high-G). This strategy effectively reduced protein interactions with Alg (as shown by model ITC and SPR experiments) and, depending on the protein type, afforded control over the protein release for at least one month. The released proteins retained their in vitro bioactivity: CXCL12 stimulated the migration of Jurkat cells, and FGF-2 and VEGF induced proliferation and maturation of HUVECs. The presence of heparin also intensified protein biological efficiency. The proposed approach for encapsulation of proteins with a positive net charge into high-G Alg hydrogels is promising for controlled long-term protein delivery under in vivo conditions. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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10 pages, 3183 KiB  
Article
Mechanical Properties of Human Concentrated Growth Factor (CGF) Membrane and the CGF Graft with Bone Morphogenetic Protein-2 (BMP-2) onto Periosteum of the Skull of Nude Mice
by Md. Arafat Kabir, Akihiro Hirakawa, Bowen Zhu, Kenji Yokozeki, Mamata Shakya, Bingzhen Huang, Toshiyuki Akazawa, Masahiro Todoh and Masaru Murata
Int. J. Mol. Sci. 2021, 22(21), 11331; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111331 - 20 Oct 2021
Cited by 6 | Viewed by 2698
Abstract
Concentrated growth factor (CGF) is 100% blood-derived, cross-linked fibrin glue with platelets and growth factors. Human CGF clot is transformed into membrane by a compression device, which has been widely used clinically. However, the mechanical properties of the CGF membranes have not been [...] Read more.
Concentrated growth factor (CGF) is 100% blood-derived, cross-linked fibrin glue with platelets and growth factors. Human CGF clot is transformed into membrane by a compression device, which has been widely used clinically. However, the mechanical properties of the CGF membranes have not been well characterized. The aims of this study were to measure the tensile strength of human CGF membrane and observe its behavior as a scaffold of BMP-2 in ectopic site over the skull. The tensile test of the full length was performed at the speed of 2mm/min. The CGF membrane (5 × 5 × 2 mm3) or the CGF/BMP-2 (1.0 μg) membrane was grafted onto the skull periosteum of nude mice (5-week-old, male), and harvested at 14 days after the graft. The appearance and size of the CGF membranes were almost same for 7 days by soaking at 4 °C in saline. The average values of the tensile strength at 0 day and 7 days were 0.24 MPa and 0.26 MPa, respectively. No significant differences of both the tensile strength and the elastic modulus were found among 0, 1, 3, and 7 days. Supra-periosteal bone induction was found at 14 days in the CGF/BMP-2, while the CGF alone did not induce bone. These results demonstrated that human CGF membrane could become a short-term, sticky fibrin scaffold for BMP-2, and might be preserved as auto-membranes for wound protection after the surgery. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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19 pages, 8757 KiB  
Article
Synthesis and Characterization of a Novel Biocompatible Alloy, Ti-Nb-Zr-Ta-Sn
by Yuliya Y. Khrunyk, Sabrina Ehnert, Stella V. Grib, Anatoly G. Illarionov, Stepan I. Stepanov, Artemiy A. Popov, Maxim A. Ryzhkov, Sergey V. Belikov, Zeqian Xu, Frank Rupp and Andreas K. Nüssler
Int. J. Mol. Sci. 2021, 22(19), 10611; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910611 - 30 Sep 2021
Cited by 9 | Viewed by 2295
Abstract
Many current-generation biomedical implants are fabricated from the Ti-6Al-4V alloy because it has many attractive properties, such as low density and biocompatibility. However, the elastic modulus of this alloy is much larger than that of the surrounding bone, leading to bone resorption and, [...] Read more.
Many current-generation biomedical implants are fabricated from the Ti-6Al-4V alloy because it has many attractive properties, such as low density and biocompatibility. However, the elastic modulus of this alloy is much larger than that of the surrounding bone, leading to bone resorption and, eventually, implant failure. In the present study, we synthesized and performed a detailed analysis of a novel low elastic modulus Ti-based alloy (Ti-28Nb-5Zr-2Ta-2Sn (TNZTS alloy)) using a variety of methods, including scanning electron microscopy, transmission electron microscopy, X-ray diffraction, and tensile test. Additionally, the in vitro biocompatibility of the TNZTS alloy was evaluated using SCP-1, SaOs-2, and THP-1 cell lines and primary human osteoblasts. Compared to Ti-6Al-4V, the elastic modulus of TNZTS alloy was significantly lower, while measures of its in vitro biocompatibility are comparable. O2 plasma treatment of the surface of the alloy significantly increased its hydrophilicity and, hence, its in vitro biocompatibility. TNZTS alloy specimens did not induce the release of cytokines by macrophages, indicating that such scaffolds would not trigger inflammatory responses. The present results suggest that the TNZTS alloy may have potential as an alternative to Ti-6Al-4V. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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18 pages, 5120 KiB  
Article
Highly Porous Fluorapatite/β-1,3-Glucan Composite for Bone Tissue Regeneration: Characterization and In-Vitro Assessment of Biomedical Potential
by Leszek Borkowski, Agata Przekora, Anna Belcarz, Krzysztof Palka, Mariusz Jojczuk, Piotr Lukasiewicz, Adam Nogalski and Grazyna Ginalska
Int. J. Mol. Sci. 2021, 22(19), 10414; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910414 - 27 Sep 2021
Cited by 10 | Viewed by 2003
Abstract
A novel fluorapatite/glucan composite (“FAP/glucan”) was developed for the treatment of bone defects. Due to the presence of polysaccharide polymer (β-1,3-glucan), the composite is highly flexible and thus very convenient for surgery. Its physicochemical and microstructural properties were evaluated using scanning electron microscopy [...] Read more.
A novel fluorapatite/glucan composite (“FAP/glucan”) was developed for the treatment of bone defects. Due to the presence of polysaccharide polymer (β-1,3-glucan), the composite is highly flexible and thus very convenient for surgery. Its physicochemical and microstructural properties were evaluated using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), mercury intrusion, mechanical testing and compared with the reference material, which was a hydroxyapatite/glucan composite (“HAP/glucan”) with hydroxyapatite granules (HAP) instead of FAP. It was found that FAP/glucan has a higher density and lower porosity than the reference material. The correlation between the Young’s modulus and the compressive strength between the materials is different in a dry and wet state. Bioactivity assessment showed a lower ability to form apatite and lower uptake of apatite-forming ions from the simulated body fluid by FAP/glucan material in comparison to the reference material. Moreover, FAP/glucan was determined to be of optimal fluoride release capacity for osteoblasts growth requirements. The results of cell culture experiments showed that fluoride-containing biomaterial was non-toxic, enhanced the synthesis of osteocalcin and stimulated the adhesion of osteogenic cells. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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17 pages, 3787 KiB  
Article
Anisotropic Chitosan Scaffolds Generated by Electrostatic Flocking Combined with Alginate Hydrogel Support Chondrogenic Differentiation
by Elke Gossla, Anne Bernhardt, Robert Tonndorf, Dilbar Aibibu, Chokri Cherif and Michael Gelinsky
Int. J. Mol. Sci. 2021, 22(17), 9341; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22179341 - 28 Aug 2021
Cited by 15 | Viewed by 2463
Abstract
The replacement of damaged or degenerated articular cartilage tissue remains a challenge, as this non-vascularized tissue has a very limited self-healing capacity. Therefore, tissue engineering (TE) of cartilage is a promising treatment option. Although significant progress has been made in recent years, there [...] Read more.
The replacement of damaged or degenerated articular cartilage tissue remains a challenge, as this non-vascularized tissue has a very limited self-healing capacity. Therefore, tissue engineering (TE) of cartilage is a promising treatment option. Although significant progress has been made in recent years, there is still a lack of scaffolds that ensure the formation of functional cartilage tissue while meeting the mechanical requirements for chondrogenic TE. In this article, we report the application of flock technology, a common process in the modern textile industry, to produce flock scaffolds made of chitosan (a biodegradable and biocompatible biopolymer) for chondrogenic TE. By combining an alginate hydrogel with a chitosan flock scaffold (CFS+ALG), a fiber-reinforced hydrogel with anisotropic properties was developed to support chondrogenic differentiation of embedded human chondrocytes. Pure alginate hydrogels (ALG) and pure chitosan flock scaffolds (CFS) were studied as controls. Morphology of primary human chondrocytes analyzed by cLSM and SEM showed a round, chondrogenic phenotype in CFS+ALG and ALG after 21 days of differentiation, whereas chondrocytes on CFS formed spheroids. The compressive strength of CFS+ALG was higher than the compressive strength of ALG and CFS alone. Chondrocytes embedded in CFS+ALG showed gene expression of chondrogenic markers (COL II, COMP, ACAN), the highest collagen II/I ratio, and production of the typical extracellular matrix such as sGAG and collagen II. The combination of alginate hydrogel with chitosan flock scaffolds resulted in a scaffold with anisotropic structure, good mechanical properties, elasticity, and porosity that supported chondrogenic differentiation of inserted human chondrocytes and expression of chondrogenic markers and typical extracellular matrix. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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15 pages, 3403 KiB  
Article
In Situ Hydroxyapatite Synthesis Enhances Biocompatibility of PVA/HA Hydrogels
by Petra Chocholata, Vlastimil Kulda, Jana Dvorakova, Monika Supova, Margit Zaloudkova and Vaclav Babuska
Int. J. Mol. Sci. 2021, 22(17), 9335; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22179335 - 28 Aug 2021
Cited by 17 | Viewed by 2203
Abstract
Bone tissue engineering tries to simulate natural behavior of hard tissues. This study aimed to produce scaffolds based on polyvinyl alcohol (PVA) and hyaluronic acid (HA) with hydroxyapatite (HAp) incorporated in two different ways, by in situ synthesis and physical mixing of pre-prepared [...] Read more.
Bone tissue engineering tries to simulate natural behavior of hard tissues. This study aimed to produce scaffolds based on polyvinyl alcohol (PVA) and hyaluronic acid (HA) with hydroxyapatite (HAp) incorporated in two different ways, by in situ synthesis and physical mixing of pre-prepared HAp. In situ synthesis resulted in calcium deficient form of HAp with lower crystallinity. The proliferation of human osteoblast-like cells MG-63 proved to be better in the scaffolds with in situ synthesized HAp compared to those with physically mixed pre-prepared HAp. For scaffolds with PVA/HA/HAp ratio 3:1:2, there was significantly higher initial adhesion (p = 0.0440), as well as the proliferation in the following days (p < 0.001). It seemed to be advantageous improve the properties of the scaffold by in situ synthesizing of HAp directly in the organic matrix. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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15 pages, 22161 KiB  
Article
Keratin-Alginate Sponges Support Healing of Partial-Thickness Burns
by Zi Kuang Moay, Luong T. H. Nguyen, Pietradewi Hartrianti, Declan P. Lunny, David Leavesley, Yee Onn Kok, Si Jack Chong, Alvin Wen Choong Chua, Shang-Ian Tee and Kee Woei Ng
Int. J. Mol. Sci. 2021, 22(16), 8594; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168594 - 10 Aug 2021
Cited by 9 | Viewed by 2942
Abstract
Deep partial-thickness burns damage most of the dermis and can cause severe pain, scarring, and mortality if left untreated. This study serves to evaluate the effectiveness of crosslinked keratin–alginate composite sponges as dermal substitutes for deep partial-thickness burns. Crosslinked keratin–alginate sponges were tested [...] Read more.
Deep partial-thickness burns damage most of the dermis and can cause severe pain, scarring, and mortality if left untreated. This study serves to evaluate the effectiveness of crosslinked keratin–alginate composite sponges as dermal substitutes for deep partial-thickness burns. Crosslinked keratin–alginate sponges were tested for the ability to support human dermal fibroblasts in vitro and to support the closure and healing of partial-thickness burn wounds in Sus scrofa pigs. Keratin–alginate composite sponges supported the enhanced proliferation of human dermal fibroblasts compared to alginate-only sponges and exhibited decreased contraction in vitro when compared to keratin only sponges. As dermal substitutes in vivo, the sponges supported the expression of keratin 14, alpha-smooth muscle actin, and collagen IV within wound sites, comparable to collagen sponges. Keratin–alginate composite sponges supported the regeneration of basement membranes in the wounds more than in collagen-treated wounds and non-grafted controls, suggesting the subsequent development of pathological scar tissues may be minimized. Results from this study indicate that crosslinked keratin–alginate sponges are suitable alternative dermal substitutes for clinical applications in wound healing and skin regeneration. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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12 pages, 690 KiB  
Article
Bacteriological Evaluation of Gingival Crevicular Fluid in Teeth Restored Using Fixed Dental Prostheses: An In Vivo Study
by Artak Heboyan, Mikayel Manrikyan, Muhammad Sohail Zafar, Dinesh Rokaya, Ruzan Nushikyan, Izabella Vardanyan, Anna Vardanyan and Zohaib Khurshid
Int. J. Mol. Sci. 2021, 22(11), 5463; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115463 - 22 May 2021
Cited by 31 | Viewed by 3200
Abstract
The present in vivo study determined the microbiological counts of the gingival crevicular fluid (GCF) among patients with fixed dental prostheses fabricated using three different techniques. A total of 129 subjects were divided into three study groups: first, cobalt-chrome-based, metal-ceramic prostheses fabricated by [...] Read more.
The present in vivo study determined the microbiological counts of the gingival crevicular fluid (GCF) among patients with fixed dental prostheses fabricated using three different techniques. A total of 129 subjects were divided into three study groups: first, cobalt-chrome-based, metal-ceramic prostheses fabricated by the conventional method (MC, n = 35); the second group consisted of cobalt-chrome-based, metal-ceramic prostheses fabricated by the computer-aided design and computer-aided manufacturing (CAD/CAM) technique (CC-MC, n = 35); the third group comprised zirconia-based ceramic prostheses fabricated using the CAD/CAM technique (CC-Zr, n = 35). The control consisted of 24 patients using prostheses fabricated with either MC, CC-MC, or CC-Zr. The GCF was obtained from the subjects before treatment, and 6 and 12 months after the prosthetic treatment. Bacteriological and bacterioscopic analysis of the GCF was performed to analyze the patients’ GCF. The data were analyzed using SPSS V20 (IBM Company, Chicago, IL, USA). The number of microorganisms of the gingival crevicular fluid in all groups at 12 months of prosthetic treatment reduced dramatically compared with the data obtained before prosthetic treatment. Inflammatory processes in the periodontium occurred slowly in the case of zirconium oxide-based ceramic constructions due to their biocompatibility with the mucous membranes and tissues of the oral cavity as well as a reduced risk of dental biofilm formation. This should be considered by dentists and prosthodontists when choosing restoration materials for subjects with periodontal pathology. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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Review

Jump to: Research

33 pages, 1671 KiB  
Review
Current Concepts of Biomaterial Scaffolds and Regenerative Therapy for Spinal Cord Injury
by Hidenori Suzuki, Yasuaki Imajo, Masahiro Funaba, Hiroaki Ikeda, Norihiro Nishida and Takashi Sakai
Int. J. Mol. Sci. 2023, 24(3), 2528; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24032528 - 28 Jan 2023
Cited by 14 | Viewed by 2949
Abstract
Spinal cord injury (SCI) is a catastrophic condition associated with significant neurological deficit and social and financial burdens. It is currently being managed symptomatically, with no real therapeutic strategies available. In recent years, a number of innovative regenerative strategies have emerged and have [...] Read more.
Spinal cord injury (SCI) is a catastrophic condition associated with significant neurological deficit and social and financial burdens. It is currently being managed symptomatically, with no real therapeutic strategies available. In recent years, a number of innovative regenerative strategies have emerged and have been continuously investigated in preclinical research and clinical trials. In the near future, several more are expected to come down the translational pipeline. Among ongoing and completed trials are those reporting the use of biomaterial scaffolds. The advancements in biomaterial technology, combined with stem cell therapy or other regenerative therapy, can now accelerate the progress of promising novel therapeutic strategies from bench to bedside. Various types of approaches to regeneration therapy for SCI have been combined with the use of supportive biomaterial scaffolds as a drug and cell delivery system to facilitate favorable cell–material interactions and the supportive effect of neuroprotection. In this review, we summarize some of the most recent insights of preclinical and clinical studies using biomaterial scaffolds in regenerative therapy for SCI and summarized the biomaterial strategies for treatment with simplified results data. One hundred and sixty-eight articles were selected in the present review, in which we focused on biomaterial scaffolds. We conducted our search of articles using PubMed and Medline, a medical database. We used a combination of “Spinal cord injury” and [“Biomaterial”, or “Scaffold”] as search terms and searched articles published up until 30 April 2022. Successful future therapies will require these biomaterial scaffolds and other synergistic approaches to address the persistent barriers to regeneration, including glial scarring, the loss of a structural framework, and biocompatibility. This database could serve as a benchmark to progress in future clinical trials for SCI using biomaterial scaffolds. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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33 pages, 3445 KiB  
Review
Bacterial Cellulose-Based Blends and Composites: Versatile Biomaterials for Tissue Engineering Applications
by Mahendra P. Raut, Emmanuel Asare, Syed Mohammad Daniel Syed Mohamed, Elliot N. Amadi and Ipsita Roy
Int. J. Mol. Sci. 2023, 24(2), 986; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24020986 - 04 Jan 2023
Cited by 17 | Viewed by 4737
Abstract
Cellulose of bacterial origin, known as bacterial cellulose (BC), is one of the most versatile biomaterials that has a huge potential in tissue engineering due to its favourable mechanical properties, high hydrophilicity, crystallinity, and purity. Additional properties such as porous nano-fibrillar 3D structure [...] Read more.
Cellulose of bacterial origin, known as bacterial cellulose (BC), is one of the most versatile biomaterials that has a huge potential in tissue engineering due to its favourable mechanical properties, high hydrophilicity, crystallinity, and purity. Additional properties such as porous nano-fibrillar 3D structure and a high degree of polymerisation of BC mimic the properties of the native extracellular matrix (ECM), making it an excellent material for the fabrication of composite scaffolds suitable for cell growth and tissue development. Recently, the fabrication of BC-based scaffolds, including composites and blends with nanomaterials, and other biocompatible polymers has received particular attention owing to their desirable properties for tissue engineering. These have proven to be promising advanced materials in hard and soft tissue engineering. This review presents the latest state-of-the-art modified/functionalised BC-based composites and blends as advanced materials in tissue engineering. Their applicability as an ideal biomaterial in targeted tissue repair including bone, cartilage, vascular, skin, nerve, and cardiac tissue has been discussed. Additionally, this review briefly summarises the latest updates on the production strategies and characterisation of BC and its composites and blends. Finally, the challenges in the future development and the direction of future research are also discussed. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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13 pages, 988 KiB  
Review
Mechanical Properties of the Modified Denture Base Materials and Polymerization Methods: A Systematic Review
by Aftab Ahmed Khan, Muhammad Amber Fareed, Abdulkarim Hussain Alshehri, Alhanoof Aldegheishem, Rasha Alharthi, Selma A. Saadaldin and Muhammad Sohail Zafar
Int. J. Mol. Sci. 2022, 23(10), 5737; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23105737 - 20 May 2022
Cited by 20 | Viewed by 3340
Abstract
Amidst growing technological advancements, newer denture base materials and polymerization methods have been introduced. During fabrication, certain mechanical properties are vital for the clinical longevity of the denture base. This systematic review aimed to explore the effect of newer denture base materials and/or [...] Read more.
Amidst growing technological advancements, newer denture base materials and polymerization methods have been introduced. During fabrication, certain mechanical properties are vital for the clinical longevity of the denture base. This systematic review aimed to explore the effect of newer denture base materials and/or polymerization methods on the mechanical properties of the denture base. An electronic database search of English peer-reviewed published papers was conducted using related keywords from 1 January 2011, up until 31 December 2021. This systematic review was based on guidelines proposed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The search identified 579 papers. However, the inclusion criteria recognized 22 papers for eligibility. The risk of bias was moderate in all studies except in two where it was observed as low. Heat cure polymethyl methacrylate (PMMA) and compression moulding using a water bath is still a widely used base material and polymerization technique, respectively. However, chemically modified PMMA using monomers, oligomers, copolymers and cross-linking agents may have a promising result. Although chemically modified PMMA resin might enhance the mechanical properties of denture base material, no clear inferences can be drawn about the superiority of any polymerization method other than the conventional compression moulding technique. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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26 pages, 1208 KiB  
Review
Progress in Bioengineering Strategies for Heart Regenerative Medicine
by Timm Häneke and Makoto Sahara
Int. J. Mol. Sci. 2022, 23(7), 3482; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23073482 - 23 Mar 2022
Cited by 13 | Viewed by 4154
Abstract
The human heart has the least regenerative capabilities among tissues and organs, and heart disease continues to be a leading cause of mortality in the industrialized world with insufficient therapeutic options and poor prognosis. Therefore, developing new therapeutic strategies for heart regeneration is [...] Read more.
The human heart has the least regenerative capabilities among tissues and organs, and heart disease continues to be a leading cause of mortality in the industrialized world with insufficient therapeutic options and poor prognosis. Therefore, developing new therapeutic strategies for heart regeneration is a major goal in modern cardiac biology and medicine. Recent advances in stem cell biology and biotechnologies such as human pluripotent stem cells (hPSCs) and cardiac tissue engineering hold great promise for opening novel paths to heart regeneration and repair for heart disease, although these areas are still in their infancy. In this review, we summarize and discuss the recent progress in cardiac tissue engineering strategies, highlighting stem cell engineering and cardiomyocyte maturation, development of novel functional biomaterials and biofabrication tools, and their therapeutic applications involving drug discovery, disease modeling, and regenerative medicine for heart disease. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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29 pages, 1397 KiB  
Review
Piezoelectric Electrospun Fibrous Scaffolds for Bone, Articular Cartilage and Osteochondral Tissue Engineering
by Frederico Barbosa, Frederico Castelo Ferreira and João Carlos Silva
Int. J. Mol. Sci. 2022, 23(6), 2907; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23062907 - 08 Mar 2022
Cited by 22 | Viewed by 5039
Abstract
Osteochondral tissue (OCT) related diseases, particularly osteoarthritis, number among the most prevalent in the adult population worldwide. However, no satisfactory clinical treatments have been developed to date to resolve this unmet medical issue. Osteochondral tissue engineering (OCTE) strategies involving the fabrication of OCT-mimicking [...] Read more.
Osteochondral tissue (OCT) related diseases, particularly osteoarthritis, number among the most prevalent in the adult population worldwide. However, no satisfactory clinical treatments have been developed to date to resolve this unmet medical issue. Osteochondral tissue engineering (OCTE) strategies involving the fabrication of OCT-mimicking scaffold structures capable of replacing damaged tissue and promoting its regeneration are currently under development. While the piezoelectric properties of the OCT have been extensively reported in different studies, they keep being neglected in the design of novel OCT scaffolds, which focus primarily on the tissue’s structural and mechanical properties. Given the promising potential of piezoelectric electrospun scaffolds capable of both recapitulating the piezoelectric nature of the tissue’s fibrous ECM and of providing a platform for electrical and mechanical stimulation to promote the regeneration of damaged OCT, the present review aims to examine the current state of the art of these electroactive smart scaffolds in OCTE strategies. A summary of the piezoelectric properties of the different regions of the OCT and an overview of the main piezoelectric biomaterials applied in OCTE applications are presented. Some recent examples of piezoelectric electrospun scaffolds developed for potentially replacing damaged OCT as well as for the bone or articular cartilage segments of this interfacial tissue are summarized. Finally, the current challenges and future perspectives concerning the use of piezoelectric electrospun scaffolds in OCT regeneration are discussed. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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14 pages, 640 KiB  
Review
New Frontiers in Peripheral Nerve Regeneration: Concerns and Remedies
by Polina Klimovich, Kseniya Rubina, Veronika Sysoeva and Ekaterina Semina
Int. J. Mol. Sci. 2021, 22(24), 13380; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222413380 - 13 Dec 2021
Cited by 15 | Viewed by 4335
Abstract
Topical advances in studying molecular and cellular mechanisms responsible for regeneration in the peripheral nervous system have highlighted the ability of the nervous system to repair itself. Still, serious injuries represent a challenge for the morphological and functional regeneration of peripheral nerves, calling [...] Read more.
Topical advances in studying molecular and cellular mechanisms responsible for regeneration in the peripheral nervous system have highlighted the ability of the nervous system to repair itself. Still, serious injuries represent a challenge for the morphological and functional regeneration of peripheral nerves, calling for new treatment strategies that maximize nerve regeneration and recovery. This review presents the canonical view of the basic mechanisms of nerve regeneration and novel data on the role of exosomes and their transferred microRNAs in intracellular communication, regulation of axonal growth, Schwann cell migration and proliferation, and stromal cell functioning. An integrated comprehensive understanding of the current mechanistic underpinnings will open the venue for developing new clinical strategies to ensure full regeneration in the peripheral nervous system. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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19 pages, 4500 KiB  
Review
Bio-Scaffolds as Cell or Exosome Carriers for Nerve Injury Repair
by Raju Poongodi, Ying-Lun Chen, Tao-Hsiang Yang, Ya-Hsien Huang, Kuender D. Yang, Hsin-Chieh Lin and Jen-Kun Cheng
Int. J. Mol. Sci. 2021, 22(24), 13347; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222413347 - 12 Dec 2021
Cited by 27 | Viewed by 5780
Abstract
Central and peripheral nerve injuries can lead to permanent paralysis and organ dysfunction. In recent years, many cell and exosome implantation techniques have been developed in an attempt to restore function after nerve injury with promising but generally unsatisfactory clinical results. Clinical outcome [...] Read more.
Central and peripheral nerve injuries can lead to permanent paralysis and organ dysfunction. In recent years, many cell and exosome implantation techniques have been developed in an attempt to restore function after nerve injury with promising but generally unsatisfactory clinical results. Clinical outcome may be enhanced by bio-scaffolds specifically fabricated to provide the appropriate three-dimensional (3D) conduit, growth-permissive substrate, and trophic factor support required for cell survival and regeneration. In rodents, these scaffolds have been shown to promote axonal regrowth and restore limb motor function following experimental spinal cord or sciatic nerve injury. Combining the appropriate cell/exosome and scaffold type may thus achieve tissue repair and regeneration with safety and efficacy sufficient for routine clinical application. In this review, we describe the efficacies of bio-scaffolds composed of various natural polysaccharides (alginate, chitin, chitosan, and hyaluronic acid), protein polymers (gelatin, collagen, silk fibroin, fibrin, and keratin), and self-assembling peptides for repair of nerve injury. In addition, we review the capacities of these constructs for supporting in vitro cell-adhesion, mechano-transduction, proliferation, and differentiation as well as the in vivo properties critical for a successful clinical outcome, including controlled degradation and re-absorption. Finally, we describe recent advances in 3D bio-printing for nerve regeneration. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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17 pages, 1699 KiB  
Review
Cellular Signalling and Photobiomodulation in Chronic Wound Repair
by Thobekile S. Leyane, Sandy W. Jere and Nicolette N. Houreld
Int. J. Mol. Sci. 2021, 22(20), 11223; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222011223 - 18 Oct 2021
Cited by 33 | Viewed by 4284
Abstract
Photobiomodulation (PBM) imparts therapeutically significant benefits in the healing of chronic wounds. Chronic wounds develop when the stages of wound healing fail to progress in a timely and orderly frame, and without an established functional and structural outcome. Therapeutic benefits associated with PBM [...] Read more.
Photobiomodulation (PBM) imparts therapeutically significant benefits in the healing of chronic wounds. Chronic wounds develop when the stages of wound healing fail to progress in a timely and orderly frame, and without an established functional and structural outcome. Therapeutic benefits associated with PBM include augmenting tissue regeneration and repair, mitigating inflammation, relieving pain, and reducing oxidative stress. PBM stimulates the mitochondria, resulting in an increase in adenosine triphosphate (ATP) production and the downstream release of growth factors. The binding of growth factors to cell surface receptors induces signalling pathways that transmit signals to the nucleus for the transcription of genes for increased cellular proliferation, viability, and migration in numerous cell types, including stem cells and fibroblasts. Over the past few years, significant advances have been made in understanding how PBM regulates numerous signalling pathways implicated in chronic wound repair. This review highlights the significant role of PBM in the activation of several cell signalling pathways involved in wound healing. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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27 pages, 2183 KiB  
Review
Functional Dental Pulp Regeneration: Basic Research and Clinical Translation
by Zhuo Xie, Zongshan Shen, Peimeng Zhan, Jiayu Yang, Qiting Huang, Shuheng Huang, Lingling Chen and Zhengmei Lin
Int. J. Mol. Sci. 2021, 22(16), 8991; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168991 - 20 Aug 2021
Cited by 60 | Viewed by 10284
Abstract
Pulpal and periapical diseases account for a large proportion of dental visits, the current treatments for which are root canal therapy (RCT) and pulp revascularisation. Despite the clinical signs of full recovery and histological reconstruction, true regeneration of pulp tissues is still far [...] Read more.
Pulpal and periapical diseases account for a large proportion of dental visits, the current treatments for which are root canal therapy (RCT) and pulp revascularisation. Despite the clinical signs of full recovery and histological reconstruction, true regeneration of pulp tissues is still far from being achieved. The goal of regenerative endodontics is to promote normal pulp function recovery in inflamed or necrotic teeth that would result in true regeneration of the pulpodentinal complex. Recently, rapid progress has been made related to tissue engineering-mediated pulp regeneration, which combines stem cells, biomaterials, and growth factors. Since the successful isolation and characterisation of dental pulp stem cells (DPSCs) and other applicable dental mesenchymal stem cells, basic research and preclinical exploration of stem cell-mediated functional pulp regeneration via cell transplantation and cell homing have received considerably more attention. Some of this effort has translated into clinical therapeutic applications, bringing a ground-breaking revolution and a new perspective to the endodontic field. In this article, we retrospectively examined the current treatment status and clinical goals of pulpal and periapical diseases and scrutinized biological studies of functional pulp regeneration with a focus on DPSCs, biomaterials, and growth factors. Then, we reviewed preclinical experiments based on various animal models and research strategies. Finally, we summarised the current challenges encountered in preclinical or clinical regenerative applications and suggested promising solutions to address these challenges to guide tissue engineering-mediated clinical translation in the future. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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