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Novel Biomaterials for Wound Healing
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Novel Biomaterials for Wound Healing

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 23685

Special Issue Editor

Dr. Shanmugasundaram Natesan

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Guest Editor
U.S. Army Institute of Surgical Research, Fort Sam Houston, San Antonio, TX, USA
Interests: burn wound healing; adipose derived stem cells; hydrogels; regenerative medicine; skin tissue engineering
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The healing of skin wounds, both acute and chronic, is recognized by the World Health Organization as a global unmet need. There are a variety of therapeutic options available to improve the healing process. However, this Special Issue will focus on advanced biomaterials capable of driving positive healing responses. Biomaterials and cells, including stem cells, are core elements of translational biomedical sciences and have provided us with a plethora of knowledge necessary to develop various technologies for wound healing and the regeneration of skin. Recent research advancements in novel wound healing platforms, ranging from bio-inspired materials to cell-derived matrices, have generated a paradigm shift in the field of wound healing. In addition to classical tissue engineering and regenerative medicine, we also welcome submissions on biomaterial development for soft tissue replacement, cell and drug delivery systems, cell interactions with material and host, and preclinical studies. We also welcome studies on cell patterning using micro/nanomaterial-based scaffolding architectures and those utilizing hybrid scaffolding strategies to enable fine-tuning of the wound microenvironment into in situ multicellular tissues through the “body as a bioreactor” concept.

The goal of this Special Issue “Advanced Biomaterials for Wound Healing” is to provide the audience a taste of the promising recent novel biomaterial strategies that have greatly advanced the field of wound healing, resulting in improved quality of life.

Dr. Shanmugasundaram Natesan
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • bio-inspired materials
  • micro/nanomaterials and drug delivery
  • tissue-engineered scaffolds
  • acute and chronic wound healing
  • hydrogel-based biomaterial

Published Papers (7 papers)

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Research

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17 pages, 6356 KiB  
Article
Dimethyl Fumarate-Loaded Transethosomes: A Formulative Study and Preliminary Ex Vivo and In Vivo Evaluation
by Francesca Ferrara, Mascia Benedusi, Franco Cervellati, Maddalena Sguizzato, Leda Montesi, Agnese Bondi, Markus Drechsler, Walter Pula, Giuseppe Valacchi and Elisabetta Esposito
Int. J. Mol. Sci. 2022, 23(15), 8756; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23158756 - 06 Aug 2022
Cited by 13 | Viewed by 2439
Abstract
In this study, transethosomes were investigated as potential delivery systems for dimethyl fumarate. A formulative study was performed investigating the effect of the composition of transethosomes on the morphology and size of vesicles, as well as drug entrapment capacity, using cryogenic transmission electron [...] Read more.
In this study, transethosomes were investigated as potential delivery systems for dimethyl fumarate. A formulative study was performed investigating the effect of the composition of transethosomes on the morphology and size of vesicles, as well as drug entrapment capacity, using cryogenic transmission electron microscopy, photon correlation spectroscopy, and HPLC. The stability of vesicles was evaluated, both for size increase and capability to control the drug degradation. Drug release kinetics and permeability profiles were evaluated in vitro using Franz cells, associated with different synthetic membranes. The in vitro viability, as well as the capacity to improve wound healing, were evaluated in human keratinocytes. Transmission electron microscopy enabled the evaluation of transethosome uptake and intracellular fate. Based on the obtained results, a transethosome gel was further formulated for the cutaneous application of dimethyl fumarate, the safety of which was evaluated in vivo with a patch test. It was found that the phosphatidylcholine concentration affected vesicle size and lamellarity, influencing the capacity to control dimethyl fumarate’s chemical stability and release kinetics. Indeed, phosphatidylcholine 2.7% w/w led to multivesicular vesicles with 344 nm mean size, controlling the drug’s chemical stability for at least 90 days. Conversely, phosphatidylcholine 0.9% w/w resulted in 130 nm sized unilamellar vesicles, which maintained 55% of the drug over 3 months. These latest kinds of transethosomes were able to improve wound healing in vitro and were easily internalised by keratinocytes. The selected transethosome gel, loading 25 mg/mL dimethyl fumarate, was not irritant after cutaneous application under occlusion, suggesting its possible suitability in the treatment of wounds caused by diabetes mellitus or peripheral vascular diseases. Full article
(This article belongs to the Special Issue Novel Biomaterials for Wound Healing)
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18 pages, 8565 KiB  
Article
Preparation of Recombinant Human Collagen III Protein Hydrogels with Sustained Release of Extracellular Vesicles for Skin Wound Healing
by Lanju Xu, Yufei Liu, Lizong Tang, Hui Xiao, Zhuo Yang and Shufang Wang
Int. J. Mol. Sci. 2022, 23(11), 6289; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23116289 - 03 Jun 2022
Cited by 15 | Viewed by 3874
Abstract
Existing treatment methods encounter difficulties in effectively promoting skin wound healing, making this a serious challenge for clinical treatment. Extracellular vesicles (EVs) secreted by stem cells have been proven to contribute to the regeneration and repair of wound tissue, but they cannot be [...] Read more.
Existing treatment methods encounter difficulties in effectively promoting skin wound healing, making this a serious challenge for clinical treatment. Extracellular vesicles (EVs) secreted by stem cells have been proven to contribute to the regeneration and repair of wound tissue, but they cannot be targeted and sustained, which seriously limits their current therapeutic potential. The recombinant human collagen III protein (rhCol III) has the advantages of good water solubility, an absence of hidden viral dangers, a low rejection rate and a stable production process. In order to achieve a site-specific sustained release of EVs, we prepared a rhCol III hydrogel by cross-linking with transglutaminase (TGase) from Streptomyces mobaraensis, which has a uniform pore size and good biocompatibility. The release profile of the rhCol III-EVs hydrogel confirmed that the rhCol III hydrogel could slowly release EVs into the external environment. Herein, the rhCol III-EVs hydrogel effectively promoted macrophage changing from type M1 to type M2, the migration ability of L929 cells and the angiogenesis of human umbilical vein endothelial cells (HUVECs). Furthermore, the rhCol III-EVs hydrogel is shown to promote wound healing by inhibiting the inflammatory response and promoting cell proliferation and angiogenesis in a diabetic rat skin injury model. The reported results indicate that the rhCol III-EVs hydrogel could be used as a new biological material for EV delivery, and has a significant application value in skin wound healing. Full article
(This article belongs to the Special Issue Novel Biomaterials for Wound Healing)
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17 pages, 2212 KiB  
Article
Tie-Over Bolster Pressure Dressing Improves Outcomes of Skin Substitutes Xenografts on Athymic Mice
by Andréanne Cartier, Martin A. Barbier, Danielle Larouche, Amélie Morissette, Ariane Bussières, Livia Montalin, Chanel Beaudoin Cloutier and Lucie Germain
Int. J. Mol. Sci. 2022, 23(10), 5507; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23105507 - 14 May 2022
Cited by 3 | Viewed by 2226
Abstract
The efficacy of skin substitutes is established for the treatment of burn injuries, but its use is not limited to this condition. This technology has the potential to improve the treatment of various conditions by offering highly advanced and personalized treatments. In vivo [...] Read more.
The efficacy of skin substitutes is established for the treatment of burn injuries, but its use is not limited to this condition. This technology has the potential to improve the treatment of various conditions by offering highly advanced and personalized treatments. In vivo studies are challenging but essential to move to clinical use in humans. Mice are the most widely used species in preclinical studies, but the main drawback of this model is the limited surface area of the graft in long-term transplantation studies caused by the displacement and the contraction of the graft. We improved the conventional surgical procedures by stabilizing the chamber covering the graft with intramuscular sutures and by adding a tie-over bolster dressing. The current study was therefore performed to compare outcomes of skin grafts between the conventional and optimized skin graft model. Human self-assembled skin substitutes (SASSs) were prepared and grafted to athymic mice either by the conventional method or by the new grafting method. Graft healing and complications were assessed using digital photographs on postoperative days 7, 14, and 21. Similar structure and organization were observed by histological staining. The new grafting method reduced medium and large displacement events by 1.26-fold and medium and large contraction events by 1.8-fold, leading to a 1.6-fold increase in graft surface area compared to skin substitutes grafted with the usual method. This innovation ensures better reproducibility and consistency of skin substitute transplants on mice. Full article
(This article belongs to the Special Issue Novel Biomaterials for Wound Healing)
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15 pages, 2208 KiB  
Article
Characterization of a Human Platelet Lysate-Loaded Keratin Hydrogel for Wound Healing Applications In Vitro
by Kameel Zuniga, Alisa Isaac, Sean Christy, Nicole Wrice, Lauren Mangum, Shanmugasundaram Natesan, Luke Burnett, Robert Christy and Christine Kowalczewski
Int. J. Mol. Sci. 2022, 23(8), 4100; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23084100 - 07 Apr 2022
Cited by 5 | Viewed by 2315
Abstract
One of the promising approaches to facilitate healing and regenerative capacity includes the application of growth-factor-loaded biomaterials. Human platelet lysate (hPL) derived from platelet-rich plasma through a freeze-thaw process has been used as a growth factor rich therapeutic in many regenerative applications. To [...] Read more.
One of the promising approaches to facilitate healing and regenerative capacity includes the application of growth-factor-loaded biomaterials. Human platelet lysate (hPL) derived from platelet-rich plasma through a freeze-thaw process has been used as a growth factor rich therapeutic in many regenerative applications. To provide sustained local delivery of the hPL-derived growth factors such as epidermal growth factor (EGF), the hPL can be loaded into biomaterials that do not degrade rapidly in vivo. Keratin (KSO), a strong filamentous protein found in human hair, when formulated as a hydrogel, is shown to sustain the release of drugs and promote wound healing. In the current study, we created a KSO biomaterial that spontaneously forms a hydrogel when rehydrated with hPL that is capable of controlled and sustained release of pro-regenerative molecules. Our study demonstrates that the release of hPL is controlled by changing the KSO hydrogel and hPL-loading concentrations, with hPL loading concentrations having a greater effect in changing release profiles. In addition, the 15% KSO concentration proved to form a stable hydrogel, and supported cell proliferation over 3 days without cytotoxic effects in vitro. The hPL-loaded keratin hydrogels show promise in potential applications for wound healing with the sustained release of pro-regenerative growth factors with easy tailoring of hydrogel properties. Full article
(This article belongs to the Special Issue Novel Biomaterials for Wound Healing)
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18 pages, 4963 KiB  
Article
The Effect of Glycerin Content in Sodium Alginate/Poly(vinyl alcohol)-Based Hydrogels for Wound Dressing Application
by Katarzyna Bialik-Wąs, Klaudia Pluta, Dagmara Malina, Mateusz Barczewski, Katarzyna Malarz and Anna Mrozek-Wilczkiewicz
Int. J. Mol. Sci. 2021, 22(21), 12022; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222112022 - 06 Nov 2021
Cited by 15 | Viewed by 3898
Abstract
The impact of different amounts of glycerin, which was used in the system of sodium alginate/poly(vinyl alcohol) (SA/PVA) hydrogel materials on the properties, such as gel fraction, swelling ability, degradation in simulated body fluids, morphological analysis, and elongation tests were presented. The study [...] Read more.
The impact of different amounts of glycerin, which was used in the system of sodium alginate/poly(vinyl alcohol) (SA/PVA) hydrogel materials on the properties, such as gel fraction, swelling ability, degradation in simulated body fluids, morphological analysis, and elongation tests were presented. The study shows a significant decrease in the gel fraction from 80.5 ± 2.1% to 45.0 ± 1.2% with the increase of glycerin content. The T5 values of the tested hydrogels were varied and range from 88.7 °C to 161.5 °C. The presence of glycerin in the matrices significantly decreased the thermal resistance, which was especially visible by T10 changes (273.9 to 163.5 °C). The degradation tests indicate that most of the tested materials do not degrade throughout the incubation period and maintain a constant ion level after 7-day incubation. The swelling abilities in distilled water and phosphate buffer solution are approximately 200–300%. However, we noticed that these values decrease with the increase in glycerin content. All tested matrices are characterized by the maximum elongation rate at break in a range of 37.6–69.5%. The FT-IR analysis exhibits glycerin changes in hydrogel structures, which is associated with the cross-linking reaction. Additionally, cytotoxicity results indicate good adhesion properties and no toxicity towards normal human dermal fibroblasts. Full article
(This article belongs to the Special Issue Novel Biomaterials for Wound Healing)
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10 pages, 41584 KiB  
Article
Efficacy of a Topical Wound Agent Methanesulfonic Acid and Dimethylsulfoxide on In Vitro Biofilms
by Saskia Schwarzer, Michael Radzieta, Slade O. Jensen and Matthew Malone
Int. J. Mol. Sci. 2021, 22(17), 9471; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22179471 - 31 Aug 2021
Cited by 5 | Viewed by 2523
Abstract
A topical desiccating wound agent containing methanesulfonic acid, dimethylsulfoxide and amorphous silica was evaluated in three in vitro models for its efficacy against biofilms produced by Pseudomonas aeruginosa (ATCC-15442) and Staphylococcus aureus (ATCC-6538). The in vitro biofilm models used were; the MBEC Assay [...] Read more.
A topical desiccating wound agent containing methanesulfonic acid, dimethylsulfoxide and amorphous silica was evaluated in three in vitro models for its efficacy against biofilms produced by Pseudomonas aeruginosa (ATCC-15442) and Staphylococcus aureus (ATCC-6538). The in vitro biofilm models used were; the MBEC Assay®, Centre for Disease Control (CDC) Biofilm Reactor® and a Semi-solid biofilm model. A 30-s exposure of a topical wound desiccating agent was used in each model. A complete eradication of viable cells was demonstrated in all models for both strains (p < 0.0001). Imaging with scanning electron microscopy (SEM) was performed where possible. All three models demonstrated complete eradication of viable cells with a 30 s application of a topical wound desiccating agent. Full article
(This article belongs to the Special Issue Novel Biomaterials for Wound Healing)
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Review

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20 pages, 1947 KiB  
Review
Current Biomaterial-Based Bone Tissue Engineering and Translational Medicine
by Jingqi Qi, Tianqi Yu, Bangyan Hu, Hongwei Wu and Hongwei Ouyang
Int. J. Mol. Sci. 2021, 22(19), 10233; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910233 - 23 Sep 2021
Cited by 52 | Viewed by 5048
Abstract
Bone defects cause significant socio-economic costs worldwide, while the clinical “gold standard” of bone repair, the autologous bone graft, has limitations including limited graft supply, secondary injury, chronic pain and infection. Therefore, to reduce surgical complexity and speed up bone healing, innovative therapies [...] Read more.
Bone defects cause significant socio-economic costs worldwide, while the clinical “gold standard” of bone repair, the autologous bone graft, has limitations including limited graft supply, secondary injury, chronic pain and infection. Therefore, to reduce surgical complexity and speed up bone healing, innovative therapies are needed. Bone tissue engineering (BTE), a new cross-disciplinary science arisen in the 21st century, creates artificial environments specially constructed to facilitate bone regeneration and growth. By combining stem cells, scaffolds and growth factors, BTE fabricates biological substitutes to restore the functions of injured bone. Although BTE has made many valuable achievements, there remain some unsolved challenges. In this review, the latest research and application of stem cells, scaffolds, and growth factors in BTE are summarized with the aim of providing references for the clinical application of BTE. Full article
(This article belongs to the Special Issue Novel Biomaterials for Wound Healing)
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