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Early Biological Reactions on Biomaterials Determining Long-Term Tissue Regeneration Effects

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Biomedical Engineering and Materials".

Deadline for manuscript submissions: closed (15 February 2022) | Viewed by 21550

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Special Issue Editors

Prof. Dr. Bilal Al-Nawas

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Guest Editor

Klinikum der Johannes-Gutenberg-Universität und Fachbereich Medizin, Mainz, Germany
Interests: dental implant; tissue regeneration; infectious diseases; preclinical models; clinical studies; biomaterials

Dr. Peer Wolfgang Kämmerer

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Guest Editor

Department of Oral and Maxillofacial Surgery, University Medical Centre Mainz, 55131 Mainz, Germany
Interests: dental implant; tissue regeneration; infectious diseases; preclinical models; clinical studies; biomaterials

Special Issue Information

Dear Colleagues,

After implantation of a biomaterial, a plethora of biological host reactions such as platelet-derived cytokine release, inflammatory or general early wound healing responses including adhesion of relevant cells and (neo-) angiogenesis take place, affecting local homeostasis. Some of these interactions have been topics of clinical and scientific discussion (e.g., the role of membranes in bone regeneration), while others are well understood (e.g., physical surface modification of implants). The goal is to specifically tailor tissue–implant interactions in order to achieve an improved and stable long-term tissue integration and regeneration. The focus of this Special Issue is interdisciplinary research on bioactive modifications of known and newly established (including 3D-printed) biomaterials with factors which are relevant for early tissue homeostasis, as well as the creation of a local wound environment that is optimal for the respective healing. In brief, methods are needed that allow the realistic and cost-efficient production of functionally improved biomaterials, contributing to patient care at a high level in the future.

Prof. Dr. Bilal Al-Nawas
Dr. Peer Wolfgang Kämmerer
Guest Editors

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Keywords

biomaterial; early interactions; homeostasis; angiogenesis; cytokines; material science

Published Papers (9 papers)

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Research

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21 pages, 8685 KiB

Open AccessArticle

Biofunctionalization of Xenogeneic Collagen Membranes with Autologous Platelet Concentrate—Influence on Rehydration Protocol and Angiogenesis

by Sebastian Blatt, Saskia-Vanessa Schröger, Andreas Pabst, Peer W. Kämmerer, Keyvan Sagheb and Bilal Al-Nawas

Biomedicines 2022, 10(3), 706; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10030706 - 18 Mar 2022

Cited by 4 | Viewed by 1838

Abstract

Background: The aim of this study was to analyze possible interactions of different xenogeneic collagen membranes (CM) and platelet-rich fibrin (PRF). PH values were evaluated in the CM rehydration process with PRF, and their influence on angiogenesis was analyzed in vivo. Materials and Methods: Porcine (Bio-Gide^®, Geistlich)- and bovine-derived collagen membranes (Symbios^®, Dentsply Sirona) were biofunctionalized with PRF by plotting process. PRF in comparison to blood, saline and a puffer pH7 solution was analysed for pH-value changes in CM rehydration process in vitro. The yolk sac membrane (YSM) model was used to investigate pro-angiogenic effects of the combination of PRF and the respective CM in comparison to native pendant by vessel in-growth and branching points after 24, 48 and 72 h evaluated light-microscopically and by immunohistochemical staining (CD105, αSMA) in vivo. Results: Significantly higher pH values were found at all points in time in PRF alone and its combined variants with Bio-Gide^® and Symbios^® compared with pure native saline solution and pH 7 solution, as well as saline with Symbios^® and Bio-Gide^® (each p < 0.01). In the YSM, vessel number and branching points showed no significant differences at 24 and 48 h between all groups (each p > 0.05). For PRF alone, a significantly increased vessel number and branching points between 24 and 48 h (each p < 0.05) and between 24 and 72 h (each p < 0.05) was shown. After 72 h, CM in combination with PRF induced a statistically significant addition to vessels and branching points in comparison with native YSM (p < 0.01) but not vs. its native pendants (p > 0.05). Summary: PRF represents a promising alternative for CM rehydration to enhance CM vascularization. Full article

(This article belongs to the Special Issue Early Biological Reactions on Biomaterials Determining Long-Term Tissue Regeneration Effects)

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19 pages, 10846 KiB

Open AccessArticle

Extracorporeal Shock Wave Therapy Improves In Vitro Formation of Multilayered Epithelium of Oral Mucosa Equivalents

by Katharina Peters, Nadine Wiesmann, Diana Heimes, Roxana Schwab, Peer W. Kämmerer, Bilal Al-Nawas, Ronald E. Unger, Annette Hasenburg and Walburgis Brenner

Biomedicines 2022, 10(3), 700; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10030700 - 18 Mar 2022

Cited by 1 | Viewed by 1564

Abstract

Oral mucosa is used in various surgical fields as a graft for the reconstruction of tissue defects. Tissue engineering of oral mucosa equivalents using autologous cells represents a suitable less burdensome alternative. The survival of the multilayered epithelium is essential for the functionality of the tissues in vivo. To ensure its functionality after transplantation, mucosa equivalents in vitro were subjected to extracorporeal shock wave therapy (ESWT) to determine whether this treatment stimulated the formation and differentiation of the epithelium. Mucosa equivalents treated with ESWT were examined for cellular metabolic activity using AlamarBlue^TM assay. The formation of vascular structures, basement membrane, and multilayered epithelium were examined using confocal fluorescence microscopy and immunohistochemistry. The potential ingrowth in vivo was simulated using the chorioallantoic membrane model (CAM assay) in ovo. ESWT on culture day 19 of oral mucosa equivalents resulted in slightly increased cellular metabolic activity. The in vitro development of basement membrane and multilayer epithelium was stimulated by ESWT. Additionally, in the CAM assay, ESWT led to a more pronounced multilayered epithelium. Thus, ESWT stimulated the formation of a more distinct and differentiated multilayered epithelium of oral mucosa equivalents in vitro and might increase the chance of efficient ingrowth, survival, and functionality of tissue equivalents in vivo. Full article

(This article belongs to the Special Issue Early Biological Reactions on Biomaterials Determining Long-Term Tissue Regeneration Effects)

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21 pages, 5148 KiB

Open AccessArticle

Surface Modification of Porous Polyethylene Implants with an Albumin-Based Nanocarrier-Release System

by Jonas Eckrich, Niklas Hoormann, Erik Kersten, Keti Piradashvili, Frederik R. Wurm, Martin Heller, Sven Becker, Toni Anusic, Juergen Brieger and Sebastian Strieth

Biomedicines 2021, 9(10), 1485; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9101485 - 16 Oct 2021

Cited by 1 | Viewed by 1816

Abstract

Background: Porous polyethylene (PPE) implants are used for the reconstruction of tissue defects but have a risk of rejection in case of insufficient ingrowth into the host tissue. Various growth factors can promote implant ingrowth, yet a long-term gradient is a prerequisite for the mediation of these effects. As modification of the implant surface with nanocarriers may facilitate a long-term gradient by sustained factor release, implants modified with crosslinked albumin nanocarriers were evaluated in vivo. Methods: Nanocarriers from murine serum albumin (MSA) were prepared by an inverse miniemulsion technique encapsulating either a low- or high-molar mass fluorescent cargo. PPE implants were subsequently coated with these nanocarriers. In control cohorts, the implant was coated with the homologue non-encapsulated cargo substance by dip coating. Implants were consequently analyzed in vivo using repetitive fluorescence microscopy utilizing the dorsal skinfold chamber in mice for ten days post implantation. Results: Implant-modification with MSA nanocarriers significantly prolonged the presence of the encapsulated small molecules while macromolecules were detectable during the investigated timeframe regardless of the form of application. Conclusions: Surface modification of PPE implants with MSA nanocarriers results in the alternation of release kinetics especially when small molecular substances are used and therefore allows a prolonged factor release for the promotion of implant integration. Full article

(This article belongs to the Special Issue Early Biological Reactions on Biomaterials Determining Long-Term Tissue Regeneration Effects)

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11 pages, 2391 KiB

Open AccessArticle

Evaluation of a Murine Model for Testing Antimicrobial Implant Materials in the Blood Circulation System

by Caroline Moerke, Marlen Kloss, Katharina Wulf, Sabine Illner, Sabine Kischkel, Martina Sombetzki, Niels Grabow, Emil Reisinger, Alper Öner and Hüseyin Ince

Biomedicines 2021, 9(10), 1464; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9101464 - 13 Oct 2021

Cited by 3 | Viewed by 1443

Abstract

Medical device-related infections are becoming a steadily increasing challenge for the health care system regarding the difficulties in the clinical treatment. In particular, cardiovascular implant infections, catheter-related infections, as well as infective endocarditis are associated with high morbidity and mortality risks for the patients. Antimicrobial materials may help to prevent medical device-associated infections and supplement the currently available therapies. In this study, we present an easy-to-handle and simplified in vivo model to test antimicrobial materials in the bloodstream of mice. The model system is composed of the implantation of a bacteria-laden micro-stent scaffold into the murine tail vein. Our model enables the simulation of catheter-related infections as well as the development of infective endocarditis specific pathologies in combination with material testing. Furthermore, this in vivo model can cover two phases of the biofilm formation, including both the local tissue response to the bacterial biofilm and the systemic inflammatory response against circulating bacteria in the bloodstream that detached from a mature biofilm. Full article

(This article belongs to the Special Issue Early Biological Reactions on Biomaterials Determining Long-Term Tissue Regeneration Effects)

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15 pages, 2498 KiB

Open AccessArticle

Zinc Oxide Nanoparticles Exhibit Favorable Properties to Promote Tissue Integration of Biomaterials

by Nadine Wiesmann, Simone Mendler, Christoph R. Buhr, Ulrike Ritz, Peer W. Kämmerer and Juergen Brieger

Biomedicines 2021, 9(10), 1462; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9101462 - 13 Oct 2021

Cited by 15 | Viewed by 2198

Abstract

Due to the demographic change, medicine faces a growing demand for tissue engineering solutions and implants. Often, satisfying tissue regeneration is difficult to achieve especially when co-morbidities hamper the healing process. As a novel strategy, we propose the incorporation of zinc oxide nanoparticles (ZnO NPs) into biomaterials to improve tissue regeneration. Due to their wide range of biocompatibility and their antibacterial properties, ZnO NPs are already discussed for different medical applications. As there are versatile possibilities of modifying their form, size, and function, they are becoming increasingly attractive for tissue engineering. In our study, in addition to antibacterial effects of ZnO NPs, we show for the first time that ZnO NPs can foster the metabolic activity of fibroblasts as well as endothelial cells, both cell types being crucial for successful implant integration. With the gelatin sponge method performed on the chicken embryo’s chorioallantoic membrane (CAM), we furthermore confirmed the high biocompatibility of ZnO NPs. In summary, we found ZnO NPs to have very favorable properties for the modification of biomaterials. Here, incorporation of ZnO NPs could help to guide the tissue reaction and promote complication-free healing. Full article

(This article belongs to the Special Issue Early Biological Reactions on Biomaterials Determining Long-Term Tissue Regeneration Effects)

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12 pages, 1966 KiB

Open AccessArticle

Novel Biodegradable Composite of Calcium Phosphate Cement and the Collagen I Mimetic P-15 for Pedicle Screw Augmentation in Osteoporotic Bone

by Harald Krenzlin, Andrea Foelger, Volker Mailänder, Christopher Blase, Marc Brockmann, Christoph Düber, Florian Ringel and Naureen Keric

Biomedicines 2021, 9(10), 1392; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9101392 - 04 Oct 2021

Cited by 4 | Viewed by 2188

Abstract

Osteoporotic vertebral fractures often necessitate fusion surgery, with high rates of implant failure. We present a novel bioactive composite of calcium phosphate cement (CPC) and the collagen I mimetic P-15 for pedicle screw augmentation in osteoporotic bone. Methods involved expression analysis of osteogenesis-related genes during osteoblastic differentiation by RT-PCR and immunostaining of osteopontin and Ca²⁺ deposits. Untreated and decalcified sheep vertebrae were utilized for linear pullout testing of pedicle screws. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DEXA). Expression of ALPI II (p < 0.0001), osteopontin (p < 0.0001), RUNX2 (p < 0.0001), and osteocalcin (p < 0.0001) was upregulated after co-culture of MSC with CPC-P-15. BMD was decreased by 28.75% ± 2.6%. Pullout loads in untreated vertebrae were 1405 ± 6 N (p < 0.001) without augmentation, 2010 ± 168 N (p < 0.0001) after augmentation with CPC-P-15, and 2112 ± 98 N (p < 0.0001) with PMMA. In decalcified vertebrae, pullout loads were 828 ± 66 N (p < 0.0001) without augmentation, 1324 ± 712 N (p = 0.04) with PMMA, and 1252 ± 131 N (p < 0.0078) with CPC-P-15. CPC-P-15 induces osteoblastic differentiation of human MES and improves pullout resistance of pedicle screws in osteoporotic and non-osteoporotic bone. Full article

(This article belongs to the Special Issue Early Biological Reactions on Biomaterials Determining Long-Term Tissue Regeneration Effects)

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27 pages, 42384 KiB

Open AccessFeature PaperArticle

Healing and Angiogenic Properties of Collagen/Chitosan Scaffolds Enriched with Hyperstable FGF2-STAB^® Protein: In Vitro, Ex Ovo and In Vivo Comprehensive Evaluation

by Lucy Vojtová, Veronika Pavliňáková, Johana Muchová, Katarína Kacvinská, Jana Brtníková, Martin Knoz, Břetislav Lipový, Martin Faldyna, Eduard Göpfert, Jakub Holoubek, Zdeněk Pavlovský, Monika Vícenová, Veronika Hefka Blahnová, Vanessa Hearnden and Eva Filová

Biomedicines 2021, 9(6), 590; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9060590 - 22 May 2021

Cited by 16 | Viewed by 4050

Abstract

Wound healing is a process regulated by a complex interaction of multiple growth factors including fibroblast growth factor 2 (FGF2). Although FGF2 appears in several tissue engineered studies, its applications are limited due to its low stability both in vitro and in vivo. Here, this shortcoming is overcome by a unique nine-point mutant of the low molecular weight isoform FGF2 retaining full biological activity even after twenty days at 37 °C. Crosslinked freeze-dried 3D porous collagen/chitosan scaffolds enriched with this hyper stable recombinant human protein named FGF2-STAB^® were tested for in vitro biocompatibility and cytotoxicity using murine 3T3-A31 fibroblasts, for angiogenic potential using an ex ovo chick chorioallantoic membrane assay and for wound healing in vivo with 3-month old white New Zealand rabbits. Metabolic activity assays indicated the positive effect of FGF2-STAB^® already at very low concentrations (0.01 µg/mL). The angiogenic properties examined ex ovo showed enhanced vascularization of the tested scaffolds. Histological evaluation and gene expression analysis by RT-qPCR proved newly formed granulation tissue at the place of a previous skin defect without significant inflammation infiltration in vivo. This work highlights the safety and biocompatibility of newly developed crosslinked collagen/chitosan scaffolds involving FGF2-STAB^® protein. Moreover, these sponges could be used as scaffolds for growing cells for dermis replacement, where neovascularization is a crucial parameter for successful skin regeneration. Full article

(This article belongs to the Special Issue Early Biological Reactions on Biomaterials Determining Long-Term Tissue Regeneration Effects)

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16 pages, 2539 KiB

Open AccessEditor’s ChoiceArticle

Does Platelet-Rich Fibrin Enhance the Early Angiogenetic Potential of Different Bone Substitute Materials? An In Vitro and In Vivo Analysis

by Sebastian Blatt, Daniel G. E. Thiem, Andreas Pabst, Bilal Al-Nawas and Peer W. Kämmerer

Biomedicines 2021, 9(1), 61; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9010061 - 10 Jan 2021

Cited by 19 | Viewed by 2787

Abstract

The impaired angiogenic potential of bone substitute materials (BSMs) may limit regenerative processes. Therefore, changes in the angiogenetic properties of different BSMs in combination with platelet-rich fibrin (PRF) in comparison to PRF alone, as well as to native BSMs, were analyzed in vitro and in vivo to evaluate possible clinical application. In vitro, four BSMs of different origins (allogeneic, alloplastic, and xenogeneic) were biofunctionalized with PRF and compared to PRF in terms of platelet interaction and growth factor release (vascular endothelial growth factor (VEGF), tissue growth factor ß (TGFß) and platelet-derived growth factor (PDGF)) after 15 min. To visualize initial cell–cell interactions, SEM was performed. In vivo, all BSMs (±PRF) were analyzed after 24 h for new-formed vessels using a chorioallantoic membrane (CAM) assay. Especially for alloplastic BSMs, the addition of PRF led to a significant consumption of platelets (p = 0.05). PDGF expression significantly decreased in comparison to PRF alone (all BSMs: p < 0.013). SEM showed the close spatial relation of each BSM and PRF. In vivo, PRF had a significant positive pro-angiogenic influence in combination with alloplastic (p = 0.007) and xenogeneic materials (p = 0.015) in comparison to the native BSMs. For bio-activated xenogeneic BSMs, the branching points were also significantly increased (p = 0.005). Finally, vessel formation was increased for BSMs and PRF in comparison to the native control (allogeneic: p = 0.046; alloplastic: p = 0.046; and xenogeneic: p = 0.050). An early enhancement of angiogenetic properties was demonstrated when combining BSMs with PRF in vitro and led to upregulated vessel formation in vivo. Thus, the use of BSMs in combination with PRF may trigger bony regeneration in clinical approaches. Full article

(This article belongs to the Special Issue Early Biological Reactions on Biomaterials Determining Long-Term Tissue Regeneration Effects)

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Review

Jump to: Research

23 pages, 3016 KiB

Open AccessReview

Inorganic Polymeric Materials for Injured Tissue Repair: Biocatalytic Formation and Exploitation

by Heinz C. Schröder, Xiaohong Wang, Meik Neufurth, Shunfeng Wang, Rongwei Tan and Werner E. G. Müller

Biomedicines 2022, 10(3), 658; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10030658 - 11 Mar 2022

Cited by 5 | Viewed by 2146

Abstract

Two biocatalytically produced inorganic biomaterials show great potential for use in regenerative medicine but also other medical applications: bio-silica and bio-polyphosphate (bio-polyP or polyP). Biosilica is synthesized by a group of enzymes called silicateins, which mediate the formation of amorphous hydrated silica from monomeric precursors. The polymeric silicic acid formed by these enzymes, which have been cloned from various siliceous sponge species, then undergoes a maturation process to form a solid biosilica material. The second biomaterial, polyP, has the extraordinary property that it not only has morphogenetic activity similar to biosilica, i.e., can induce cell differentiation through specific gene expression, but also provides metabolic energy through enzymatic cleavage of its high-energy phosphoanhydride bonds. This reaction is catalyzed by alkaline phosphatase, a ubiquitous enzyme that, in combination with adenylate kinase, forms adenosine triphosphate (ATP) from polyP. This article attempts to highlight the biomedical importance of the inorganic polymeric materials biosilica and polyP as well as the enzymes silicatein and alkaline phosphatase, which are involved in their metabolism or mediate their biological activity. Full article

(This article belongs to the Special Issue Early Biological Reactions on Biomaterials Determining Long-Term Tissue Regeneration Effects)

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