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Biomaterials for Soft and Hard Tissue Regeneration 2.0

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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 (30 April 2022) | Viewed by 18154

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Special Issue Editors

Dr. Mike Barbeck

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Guest Editor

1. BerlinAnalytix GmbH, Ullsteinstrasse 109, 12109 Berlin, Germany
2. Department of Ceramic Materials, Chair of Advanced Ceramic Materials, Institute for Materials Science and Technologies, Technical University Berlin, Berlin, Germany
Interests: dental barrier membranes; collagen; cross-linking; magnesium membranes; degradation; bone tissue regeneration
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Dr. Ole Jung

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Clinic and Policlinic for Dermatology and Venereology, University Medical Center Rostock, 18057 Rostock, Germany
Interests: magnesium; surfaces; coating technologies; biomaterials
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Prof. Dr. Stevo Najman

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1. Department of Biology and Human Genetics, Faculty of Medicine, University of Niš, 18000 Niš, Serbia
2. Department for Cell and Tissue Engineering, Scientific Research Center for Biomedicine, Faculty of Medicine, University of Niš, 18000 Niš, Serbia
Interests: skeletal tissues regeneration assisted by biomaterials and stem cells; biomaterials; tissue engineering models; regenerative medicine; examination of biological activity and toxicity of the various substances in animal models in vivo and cell models in vitro; macrophages; stem cells; cell and molecular biology; human genetics
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Special Issue Information

Dear Colleagues,

The regeneration of hard and soft tissues aided by biomaterials is of great clinical relevance. A variety of biomaterials for both soft and hard tissue indications are already available as well as a large number of adaptations that are continually being developed. Moreover, radically new and smart materials as well as manufacturing methods are in the focus of biomaterial research. Altogether, these biomaterials are engineered to be bioactive or bioresorbable, whilst also promoting tissue regeneration to the state of a restitutio ad integrum. For both the analysis of scientific issues that are still unsolved and for the evaluation of the biocompatibility of biomaterials, preclinical in vitro and in vivo studies, as well as clinical investigations are mandatory.

In this special issue, we would like to present new insights into the underlying cellular and molecular interactions of biomaterials for hard and soft tissue regeneration. Particularly, this special issue seeks for studies describing radically new and smart materials, innovative material processing techniques as well as interactions of materials of both classes with the immune system and relations of immune responses to biomaterials with healing processes. Thus, contributions (reviews and/or original papers) on new biomaterials for hard and soft tissue regeneration and cellular or molecular interactions with biomaterials are welcome.

Dr. Mike Barbeck
Dr. Ole Jung
Prof. Dr. Stevo Najman
Guest Editors

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Keywords

hard and soft tissue regeneration
smart biomaterials
innovative material processing techniques
immune responses to biomaterials
molecular interactions with smart biomaterials

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Published Papers (6 papers)

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Research

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12 pages, 3927 KiB

Open AccessArticle

Novel Elastic Threads for Intestinal Anastomoses: Feasibility and Mechanical Evaluation in a Porcine and Rabbit Model

by Sophia M. Schmitz, Marius J. Helmedag, Klas-Moritz Kossel, Roman M. Eickhoff, Daniel Heise, Andreas Kroh, Mare Mechelinck, Thomas Gries, Stefan Jockenhoevel, Ulf P. Neumann and Andreas Lambertz

Int. J. Mol. Sci. 2022, 23(10), 5389; https://doi.org/10.3390/ijms23105389 - 11 May 2022

Cited by 1 | Viewed by 2284

Abstract

Gastrointestinal anastomoses are an important source of postoperative complications. In particular, the ideal suturing material is still the subject of investigation. Therefore, this study aimed to evaluate a newly developed suturing material with elastic properties made from thermoplastic polyurethane (TPU); Polyvinylidene fluoride (PVDF) and TPU were tested in two different textures (round and a modified, “snowflake” structure) in 32 minipigs, with two anastomoses of the small intestine sutured 2 m apart. After 90 days, the anastomoses were evaluated for inflammation, the healing process, and foreign body reactions. A computer-assisted immunohistological analysis of staining for Ki67, CD68, smooth muscle actin (SMA), and Sirius red was performed using TissueFAXS. Additionally, the in vivo elastic properties of the material were assessed by measuring the suture tension in a rabbit model. Each suture was tested twice in three rabbits; No major surgical complications were observed and all anastomoses showed adequate wound healing. The Ki67+ count and SMA area differed between the groups (F (3, 66) = 5.884, p = 0.0013 and F (3, 56) = 6.880, p = 0.0005, respectively). In the TPU-snowflake material, the Ki67+ count was the lowest, while the SMA area provided the highest values. The CD68+ count and collagen I/III ratio did not differ between the groups (F (3, 69) = 2.646, p = 0.0558 and F (3, 54) = 0.496, p = 0.686, respectively). The suture tension measurements showed a significant reduction in suture tension loss for both the TPU threads; Suturing material made from TPU with elastic properties proved applicable for intestinal anastomoses in a porcine model. In addition, our results suggest a successful reduction in tissue incision and an overall suture tension homogenization. Full article

(This article belongs to the Special Issue Biomaterials for Soft and Hard Tissue Regeneration 2.0)

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16 pages, 1778 KiB

Open AccessArticle

Site-Directed Immobilization of an Engineered Bone Morphogenetic Protein 2 (BMP2) Variant to Collagen-Based Microspheres Induces Bone Formation In Vivo

by Claudia Siverino, Shorouk Fahmy-Garcia, Didem Mumcuoglu, Heike Oberwinkler, Markus Muehlemann, Thomas Mueller, Eric Farrell, Gerjo J. V. M. van Osch and Joachim Nickel

Int. J. Mol. Sci. 2022, 23(7), 3928; https://doi.org/10.3390/ijms23073928 - 1 Apr 2022

Cited by 5 | Viewed by 2222

Abstract

For the treatment of large bone defects, the commonly used technique of autologous bone grafting presents several drawbacks and limitations. With the discovery of the bone-inducing capabilities of bone morphogenetic protein 2 (BMP2), several delivery techniques were developed and translated to clinical applications. Implantation of scaffolds containing adsorbed BMP2 showed promising results. However, off-label use of this protein-scaffold combination caused severe complications due to an uncontrolled release of the growth factor, which has to be applied in supraphysiological doses in order to induce bone formation. Here, we propose an alternative strategy that focuses on the covalent immobilization of an engineered BMP2 variant to biocompatible scaffolds. The new BMP2 variant harbors an artificial amino acid with a specific functional group, allowing a site-directed covalent scaffold functionalization. The introduced artificial amino acid does not alter BMP2′s bioactivity in vitro. When applied in vivo, the covalently coupled BMP2 variant induces the formation of bone tissue characterized by a structurally different morphology compared to that induced by the same scaffold containing ab-/adsorbed wild-type BMP2. Our results clearly show that this innovative technique comprises translational potential for the development of novel osteoinductive materials, improving safety for patients and reducing costs. Full article

(This article belongs to the Special Issue Biomaterials for Soft and Hard Tissue Regeneration 2.0)

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16 pages, 8286 KiB

Open AccessArticle

In Vivo Biocompatibility Investigation of an Injectable Calcium Carbonate (Vaterite) as a Bone Substitute including Compositional Analysis via SEM-EDX Technology

by Ronald E. Unger, Sanja Stojanovic, Laura Besch, Said Alkildani, Romina Schröder, Ole Jung, Caroline Bogram, Oliver Görke, Stevo Najman, Wolfgang Tremel and Mike Barbeck

Int. J. Mol. Sci. 2022, 23(3), 1196; https://doi.org/10.3390/ijms23031196 - 21 Jan 2022

Cited by 12 | Viewed by 2548

Abstract

Injectable bone substitutes (IBS) are increasingly being used in the fields of orthopedics and maxillofacial/oral surgery. The rheological properties of IBS allow for proper and less invasive filling of bony defects. Vaterite is the most unstable crystalline polymorph of calcium carbonate and is known to be able to transform into hydroxyapatite upon contact with an organic fluid (e.g., interstitial body fluid). Two different concentrations of hydrogels based on poly(ethylene glycol)-acetal-dimethacrylat (PEG-a-DMA), i.e., 8% (w/v) (VH-A) or 10% (w/v) (VH-B), were combined with vaterite nanoparticles and implanted in subcutaneous pockets of BALB/c mice for 15 and 30 days. Explants were prepared for histochemical staining and immunohistochemical detection methods to determine macrophage polarization, and energy-dispersive X-ray analysis (EDX) to analyze elemental composition was used for the analysis. The histopathological analysis revealed a comparable moderate tissue reaction to the hydrogels mainly involving macrophages. Moreover, the hydrogels underwent a slow cellular infiltration, revealing a different degradation behavior compared to other IBS. The immunohistochemical detection showed that M1 macrophages were mainly found at the material surfaces being involved in the cell-mediated degradation and tissue integration, while M2 macrophages were predominantly found within the reactive connective tissue. Furthermore, the histomorphometrical analysis revealed balanced numbers of pro- and anti-inflammatory macrophages, demonstrating that both hydrogels are favorable materials for bone tissue regeneration. Finally, the EDX analysis showed a stepwise transformation of the vaterite particle into hydroxyapatite. Overall, the results of the present study demonstrate that hydrogels including nano-vaterite particles are biocompatible and suitable for bone tissue regeneration applications. Full article

(This article belongs to the Special Issue Biomaterials for Soft and Hard Tissue Regeneration 2.0)

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23 pages, 8876 KiB

Open AccessArticle

Ex Vivo and In Vivo Analysis of a Novel Porcine Aortic Patch for Vascular Reconstruction

by Ignacio Stöwe, Jens Pissarek, Pia Moosmann, Annica Pröhl, Sven Pantermehl, James Bielenstein, Milena Radenkovic, Ole Jung, Stevo Najman, Said Alkildani and Mike Barbeck

Int. J. Mol. Sci. 2021, 22(14), 7623; https://doi.org/10.3390/ijms22147623 - 16 Jul 2021

Cited by 6 | Viewed by 2975

Abstract

(1) Background: The aim of the present study was the biocompatibility analysis of a novel xenogeneic vascular graft material (PAP) based on native collagen won from porcine aorta using the subcutaneous implantation model up to 120 days post implantationem. As a control, an already commercially available collagen-based vessel graft (XenoSure^®) based on bovine pericardium was used. Another focus was to analyze the (ultra-) structure and the purification effort. (2) Methods: Established methodologies such as the histological material analysis and the conduct of the subcutaneous implantation model in Wistar rats were applied. Moreover, established methods combining histological, immunohistochemical, and histomorphometrical procedures were applied to analyze the tissue reactions to the vessel graft materials, including the induction of pro- and anti-inflammatory macrophages to test the immune response. (3) Results: The results showed that the PAP implants induced a special cellular infiltration and host tissue integration based on its three different parts based on the different layers of the donor tissue. Thereby, these material parts induced a vascularization pattern that branches to all parts of the graft and altogether a balanced immune tissue reaction in contrast to the control material. (4) Conclusions: PAP implants seemed to be advantageous in many aspects: (i) cellular infiltration and host tissue integration, (ii) vascularization pattern that branches to all parts of the graft, and (iii) balanced immune tissue reaction that can result in less scar tissue and enhanced integrative healing patterns. Moreover, the unique trans-implant vascularization can provide unprecedented anti-infection properties that can avoid material-related bacterial infections. Full article

(This article belongs to the Special Issue Biomaterials for Soft and Hard Tissue Regeneration 2.0)

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23 pages, 10880 KiB

Open AccessArticle

In Vivo Analysis of the Biocompatibility and Bone Healing Capacity of a Novel Bone Grafting Material Combined with Hyaluronic Acid

by Annica Pröhl, Milijana Batinic, Said Alkildani, Michael Hahn, Milena Radenkovic, Stevo Najman, Ole Jung and Mike Barbeck

Int. J. Mol. Sci. 2021, 22(9), 4818; https://doi.org/10.3390/ijms22094818 - 1 May 2021

Cited by 21 | Viewed by 3492

Abstract

The present in vivo study analyses both the inflammatory tissue reactions and the bone healing capacity of a newly developed bone substitute material (BSM) based on xenogeneic bone substitute granules combined with hyaluronate (HY) as a water-binding molecule. The results of the hyaluronate containing bone substitute material (BSM) were compared to a control xenogeneic BSM of the same chemical composition and a sham operation group up to 16 weeks post implantationem. A major focus of the study was to analyze the residual hyaluronate and its effects on the material-dependent healing behavior and the inflammatory tissue responses. The study included 63 male Wistar rats using the calvaria implantation model for 2, 8, and 16 weeks post implantationem. Established and Good Laboratory Practice (GLP)-conforming histological, histopathological, and histomorphometrical analysis methods were conducted. The results showed that the new hyaluronate containing BSM was gradually integrated within newly formed bone up to the end of the study that ended in a condition of complete bone defect healing. Thereby, no differences to the healing capacity of the control BSM were found. However, the bone formation in both groups was continuously significantly higher compared to the sham operation group. Additionally, no differences in the (inflammatory) tissue response that was analyzed via qualitative and (semi-) quantitative methods were found. Interestingly, no differences were found between the numbers of pro- and anti-inflammatory macrophages between the three study groups over the entire course of the study. No signs of the HY as a water-binding part of the BSM were histologically detectable at any of the study time points, altogether the results of the present study show that HY allows for an optimal material-associated bone tissue healing comparable to the control xenogeneic BSM. The added HY seems to be degraded within a very short time period of less than 2 weeks so that the remaining BSM granules allow for a gradual osteoconductive bone regeneration. Additionally, no differences between the inflammatory tissue reactions in both material groups and the sham operation group were found. Thus, the new hyaluronate containing xenogeneic BSM and also the control BSM have been shown to be fully biocompatible without any differences regarding bone regeneration. Full article

(This article belongs to the Special Issue Biomaterials for Soft and Hard Tissue Regeneration 2.0)

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Review

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26 pages, 1072 KiB

Open AccessReview

Interaction of Ceramic Implant Materials with Immune System

by Guzel Rafikova, Svetlana Piatnitskaia, Elena Shapovalova, Svyatoslav Chugunov, Victor Kireev, Daria Ialiukhova, Azat Bilyalov, Valentin Pavlov and Julia Kzhyshkowska

Int. J. Mol. Sci. 2023, 24(4), 4200; https://doi.org/10.3390/ijms24044200 - 20 Feb 2023

Cited by 11 | Viewed by 3315

Abstract

The immuno-compatibility of implant materials is a key issue for both initial and long-term implant integration. Ceramic implants have several advantages that make them highly promising for long-term medical solutions. These beneficial characteristics include such things as the material availability, possibility to manufacture various shapes and surface structures, osteo-inductivity and osteo-conductivity, low level of corrosion and general biocompatibility. The immuno-compatibility of an implant essentially depends on the interaction with local resident immune cells and, first of all, macrophages. However, in the case of ceramics, these interactions are insufficiently understood and require intensive experimental examinations. Our review summarizes the state of the art in variants of ceramic implants: mechanical properties, different chemical modifications of the basic material, surface structures and modifications, implant shapes and porosity. We collected the available information about the interaction of ceramics with the immune system and highlighted the studies that reported ceramic-specific local or systemic effects on the immune system. We disclosed the gaps in knowledge and outlined the perspectives for the identification to ceramic-specific interactions with the immune system using advanced quantitative technologies. We discussed the approaches for ceramic implant modification and pointed out the need for data integration using mathematic modelling of the multiple ceramic implant characteristics and their contribution for long-term implant bio- and immuno-compatibility. Full article

(This article belongs to the Special Issue Biomaterials for Soft and Hard Tissue Regeneration 2.0)

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