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Biomedicines
Special Issues
Soft and Hard Tissue Regeneration
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Soft and Hard Tissue Regeneration

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

Deadline for manuscript submissions: closed (30 November 2020) | Viewed by 40450

Special Issue Editors

Dr. Mike Barbeck

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Guest Editor
Clinic and Policlinic for Dermatology and Venereology, University Medical Center Rostock, 18057 Rostock, Germany
Interests: bone substitutes; collagen-based biomaterials for soft and hard tissue regeneration; foreign body response to biomaterials; inflammation; macrophages; multinucleated giant cells, degradation processes of biomaterials; phagocytosis; vascularization; histology; immunohistochemistry; histomorphometry
Special Issues, Collections and Topics in MDPI journals
Dr. Ole Jung

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Guest Editor
Clinic and Policlinic for Dermatology and Venereology, University Medical Center Rostock, 18057 Rostock, Germany
Interests: tissue engineering; bone susbtitute materials (BSM); guided bone/tissue ergeneration (GBR/GTR); coating technologies; magnesium; metallic degradation; alloy development; in vivo
Dr. Michael Dau

E-Mail Website
Guest Editor
Department of Oral, Maxillofacial Plastic Surgery, University Medical Center Rostock, Rostock, Germany
Interests: bone substitute material, bone remodelling, bone healing, dental implant, animal models, tissue integration

Special Issue Information

Dear Colleagues,

A variety of biomaterials are currently avaliable on the market for soft and hard tissue regeneration. Moreover, a broad spectrum of new materials is currently developed worldwide. Thus, an enormous number of preclinical in vitro and in vivo studies and also clinical studies are conducted to clarify the related tissue reactions and their regenerative capacities. The compositions of the biomaterials for soft and hard tissue regeneration vary from natural polymers such as collagen and decellularized bone matrix up to synthetic polymers such as polylactid acid (PLA). Furthermore, different new composite materials and metals (e.g., magnesium) are currently being developed and investigated. Moreover, new manufacturing methods such as 3D printing are on the rise and can be of greater interest for future applications. Finally, it is of great interest to conduct further research focusing on the molecular mechanisms and the immunological response to biomaterials.

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 studies describing both new and already available biomaterials, and innovative material processing techniques related to the healing processes of soft and hard tissues. Thus, contributions (reviews and/or original papers) on biomaterials for hard and soft tissue regeneration are very welcome.

Dr. Ole Jung
Dr. Mike Barbeck
Guest Editors

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. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). 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.

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Related Special Issue

Published Papers (10 papers)

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Editorial

Jump to: Research, Review

3 pages, 190 KiB  
Editorial
Editorial of the Special Issue: “Soft and Hard Tissue Regeneration”
by Mike Barbeck, Said Alkildani and Ole Jung
Biomedicines 2022, 10(2), 356; https://doi.org/10.3390/biomedicines10020356 - 1 Feb 2022
Cited by 1 | Viewed by 1448
Abstract
In general, only a total of four tissue classes are distinguished: the covering tissue (epithelial tissue), the connective and supporting tissue (connective tissue, fatty tissue, bone, and cartilage), the muscle tissue, and the nervous tissue [...] Full article
(This article belongs to the Special Issue Soft and Hard Tissue Regeneration)

Research

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12 pages, 3854 KiB  
Article
Collagen-Based Matrices for Osteoconduction: A Preclinical In Vivo Study
by Hiroki Katagiri, Yacine El Tawil, Niklaus P. Lang, Jean-Claude Imber, Anton Sculean, Masako Fujioka-Kobayashi and Nikola Saulacic
Biomedicines 2021, 9(2), 143; https://doi.org/10.3390/biomedicines9020143 - 2 Feb 2021
Cited by 4 | Viewed by 2211
Abstract
The aim of this study was to evaluate the influence of additional hydroxyapatite (HA) in collagen-based matrices (CM) and membrane placement on bone formation in calvarial defects. Critical size defects in the calvaria of 16 New Zealand White Rabbits were randomly treated with [...] Read more.
The aim of this study was to evaluate the influence of additional hydroxyapatite (HA) in collagen-based matrices (CM) and membrane placement on bone formation in calvarial defects. Critical size defects in the calvaria of 16 New Zealand White Rabbits were randomly treated with CM or mineralized collagen-based matrices (mCM). Half of the sites were covered with a collagen membrane. Animals were euthanized after 12 weeks of healing. The samples were studied by micro-CT and histology. Newly formed lamellar bone was observed in all samples at the periphery of the defect. In the central areas, however, new bone composed of both woven and lamellar bone was embedded in the soft tissue. Samples treated with mCM showed more residual biomaterial and induced more small bony islands in the central areas of the defects than samples with CM. Nevertheless, a complete defect closure was not observed in any of the samples at 12 weeks. Membrane placement resulted in a decrease in bone density and height. Significant differences between the groups were revealed only between CM groups with and without membrane coverage for bone height in the central area of the defect. Neither mineralization of CM nor membrane placement improved the osteogenic capacity in this particular defect. Nevertheless, mineralisation influenced bone density without a membrane placement and bone volume underneath a membrane. CM may be used as a scaffold in bone regeneration procedures, without the need of a membrane coverage. Further preclinical studies are warrant to optimise the potential of mCM. Full article
(This article belongs to the Special Issue Soft and Hard Tissue Regeneration)
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17 pages, 10752 KiB  
Article
Biocompatibility and Immune Response of a Newly Developed Volume-Stable Magnesium-Based Barrier Membrane in Combination with a PVD Coating for Guided Bone Regeneration (GBR)
by Larissa Steigmann, Ole Jung, Wolfgang Kieferle, Sanja Stojanovic, Annica Proehl, Oliver Görke, Steffen Emmert, Stevo Najman, Mike Barbeck and Daniel Rothamel
Biomedicines 2020, 8(12), 636; https://doi.org/10.3390/biomedicines8120636 - 20 Dec 2020
Cited by 20 | Viewed by 3852
Abstract
To date, there are no bioresorbable alternatives to non-resorbable and volume-stable membranes in the field of dentistry for guided bone or tissue regeneration (GBR/GTR). Even magnesium (Mg) has been shown to constitute a favorable biomaterial for the development of stabilizing structures. However, it [...] Read more.
To date, there are no bioresorbable alternatives to non-resorbable and volume-stable membranes in the field of dentistry for guided bone or tissue regeneration (GBR/GTR). Even magnesium (Mg) has been shown to constitute a favorable biomaterial for the development of stabilizing structures. However, it has been described that it is necessary to prevent premature degradation to ensure both the functionality and the biocompatibility of such Mg implants. Different coating strategies have already been developed, but most of them did not provide the desired functionality. The present study analyses a new approach based on ion implantation (II) with PVD coating for the passivation of a newly developed Mg membrane for GBR/GTR procedures. To demonstrate comprehensive biocompatibility and successful passivation of the Mg membranes, untreated Mg (MG) and coated Mg (MG-Co) were investigated in vitro and in vivo. Thereby a collagen membrane with an already shown biocompatibility was used as control material. All investigations were performed according to EN ISO 10993 regulations. The in vitro results showed that both the untreated and PVD-coated membranes were not cytocompatible. However, both membrane types fulfilled the requirements for in vivo biocompatibility. Interestingly, the PVD coating did not have an influence on the gas cavity formation compared to the uncoated membrane, but it induced lower numbers of anti-inflammatory macrophages in comparison to the pure Mg membrane and the collagen membrane. In contrast, the pure Mg membrane provoked an immune response that was fully comparable to the collagen membrane. Altogether, this study shows that pure magnesium membranes represent a promising alternative compared to the nonresorbable volume-stable materials for GBR/GTR therapy. Full article
(This article belongs to the Special Issue Soft and Hard Tissue Regeneration)
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14 pages, 9751 KiB  
Article
Continuous Electrical Stimulation Affects Initial Growth and Proliferation of Adipose-Derived Stem Cells
by Peer W. Kämmerer, Vivien Engel, Franz Plocksties, Anika Jonitz-Heincke, Dirk Timmermann, Nadja Engel, Bernhard Frerich, Rainer Bader, Daniel G. E. Thiem, Anna Skorska, Robert David, Bilal Al-Nawas and Michael Dau
Biomedicines 2020, 8(11), 482; https://doi.org/10.3390/biomedicines8110482 - 8 Nov 2020
Cited by 15 | Viewed by 3303
Abstract
The aim of the study was to establish electrical stimulation parameters in order to improve cell growth and viability of human adipose-derived stem cells (hADSC) when compared to non-stimulated cells in vitro. hADSC were exposed to continuous electrical stimulation with 1.7 V AC/20 [...] Read more.
The aim of the study was to establish electrical stimulation parameters in order to improve cell growth and viability of human adipose-derived stem cells (hADSC) when compared to non-stimulated cells in vitro. hADSC were exposed to continuous electrical stimulation with 1.7 V AC/20 Hz. After 24, 72 h and 7 days, cell number, cellular surface coverage and cell proliferation were assessed. In addition, cell cycle analysis was carried out after 3 and 7 days. After 24 h, no significant alterations were observed for stimulated cells. At day 3, stimulated cells showed a 4.5-fold increase in cell numbers, a 2.7-fold increase in cellular surface coverage and a significantly increased proliferation. Via cell cycle analysis, a significant increase in the G2/M phase was monitored for stimulated cells. Contrastingly, after 7 days, the non-stimulated group exhibited a 11-fold increase in cell numbers and a 4-fold increase in cellular surface coverage as well as a significant increase in cell proliferation. Moreover, the stimulated cells displayed a shift to the G1 and sub-G1 phase, indicating for metabolic arrest and apoptosis initiation. In accordance, continuous electrical stimulation of hADSC led to a significantly increased cell growth and proliferation after 3 days. However, longer stimulation periods such as 7 days caused an opposite result indicating initiation of apoptosis. Full article
(This article belongs to the Special Issue Soft and Hard Tissue Regeneration)
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27 pages, 5233 KiB  
Article
Development of a Multifunctional Bioerodible Nanocomposite Containing Metronidazole and Curcumin to Apply on L-PRF Clot to Promote Tissue Regeneration in Dentistry
by Denise Murgia, Giuseppe Angellotti, Alice Conigliaro, Francesco Carfi Pavia, Fabio D'Agostino, Marco Contardi, Rodolfo Mauceri, Riccardo Alessandro, Giuseppina Campisi and Viviana De Caro
Biomedicines 2020, 8(10), 425; https://doi.org/10.3390/biomedicines8100425 - 16 Oct 2020
Cited by 18 | Viewed by 4431
Abstract
Teeth extractions are often followed by alveolar bone reabsorption, although an adequate level of bone is required for reliable rehabilitations by dental implants. Leukocyte and platelet-rich fibrin (L-PRF) has been widely applied in regenerative procedures and with antibiotic and antioxidant agents could play [...] Read more.
Teeth extractions are often followed by alveolar bone reabsorption, although an adequate level of bone is required for reliable rehabilitations by dental implants. Leukocyte and platelet-rich fibrin (L-PRF) has been widely applied in regenerative procedures and with antibiotic and antioxidant agents could play an essential role in hard and soft tissue healing. In this work, a nanocomposite (Sponge-C-MTR) consisting of a hyaluronate-based sponge loaded with metronidazole (MTR) and nanostructured lipid carriers containing curcumin (CUR-NLC) was designed to be wrapped in the L-PRF™ membrane in the post-extraction sockets and characterized. CUR-NLCs, obtained by homogenization followed by high-frequency sonication of the lipid mixture, showed loading capacity (5% w/w), drug recovery (95% w/w), spherical shape with an average particle size of 112.0 nm, and Zeta potential of −24 mV. Sponge-C-MTR was obtained by entrapping CUR-NLC in a hydrophilic matrix by a freeze-drying process, and physico-chemical and cytocompatibility properties were evaluated. Moreover, the aptitude of CUR and MTR to the penetrate and/or permeate both L-PRF™ and porcine buccal tissue was assessed, highlighting MTR penetration and CUR accumulation promoted by the system. The results positively support the action of nanocomposite in dental tissues regeneration when applied together with the L-PRF™. Full article
(This article belongs to the Special Issue Soft and Hard Tissue Regeneration)
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Graphical abstract

21 pages, 5307 KiB  
Article
Insights into Biomechanical and Proteomic Characteristics of Small Diameter Vascular Grafts Utilizing the Human Umbilical Artery
by Panagiotis Mallis, Dimitrios P. Sokolis, Manousos Makridakis, Jerome Zoidakis, Athanasios D. Velentzas, Michalis Katsimpoulas, Antonia Vlahou, Alkiviadis Kostakis, Catherine Stavropoulos-Giokas and Efstathios Michalopoulos
Biomedicines 2020, 8(8), 280; https://doi.org/10.3390/biomedicines8080280 - 10 Aug 2020
Cited by 14 | Viewed by 2982
Abstract
The gold standard vascular substitutes, used in cardiovascular surgery, are the Dacron or expanded polytetrafluoroethylene (ePTFE)-derived grafts. However, major adverse reactions accompany their use. For this purpose, decellularized human umbilical arteries (hUAs) may be proven as a significant source for the development of [...] Read more.
The gold standard vascular substitutes, used in cardiovascular surgery, are the Dacron or expanded polytetrafluoroethylene (ePTFE)-derived grafts. However, major adverse reactions accompany their use. For this purpose, decellularized human umbilical arteries (hUAs) may be proven as a significant source for the development of small diameter conduits. The aim of this study was the evaluation of a decellularization protocol in hUAs. To study the effect of the decellularization to the hUAs, histological analysis was performed. Then, native and decellularized hUAs were biochemically and biomechanically evaluated. Finally, broad proteomic analysis was applied. Histological analysis revealed the successful decellularization of the hUAs. Furthermore, a great amount of DNA was removed from the decellularized hUAs. Biomechanical analysis revealed statistically significant differences in longitudinal direction only in maximum stress (p < 0.013) and strain (p < 0.001). On the contrary, all parameters tested for circumferential direction exhibited significant differences (p < 0.05). Proteomic analysis showed the preservation of the extracellular matrix and cytoskeletal proteins in both groups. Proteomic data are available via ProteomeXchange with identifier PXD020187. The above results indicated that hUAs were efficiently decellularized. The tissue function properties of these conduits were well retained, making them ideal candidates for the development of small diameter vascular grafts. Full article
(This article belongs to the Special Issue Soft and Hard Tissue Regeneration)
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Review

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33 pages, 32895 KiB  
Review
3D Printing for Soft Tissue Regeneration and Applications in Medicine
by Sven Pantermehl, Steffen Emmert, Aenne Foth, Niels Grabow, Said Alkildani, Rainer Bader, Mike Barbeck and Ole Jung
Biomedicines 2021, 9(4), 336; https://doi.org/10.3390/biomedicines9040336 - 26 Mar 2021
Cited by 15 | Viewed by 4261
Abstract
The use of additive manufacturing (AM) technologies is a relatively young research area in modern medicine. This technology offers a fast and effective way of producing implants, tissues, or entire organs individually adapted to the needs of a patient. Today, a large number [...] Read more.
The use of additive manufacturing (AM) technologies is a relatively young research area in modern medicine. This technology offers a fast and effective way of producing implants, tissues, or entire organs individually adapted to the needs of a patient. Today, a large number of different 3D printing technologies with individual application areas are available. This review is intended to provide a general overview of these various printing technologies and their function for medical use. For this purpose, the design and functionality of the different applications are presented and their individual strengths and weaknesses are explained. Where possible, previous studies using the respective technologies in the field of tissue engineering are briefly summarized. Full article
(This article belongs to the Special Issue Soft and Hard Tissue Regeneration)
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15 pages, 572 KiB  
Review
Quercetin-Based Nanocomposites as a Tool to Improve Dental Disease Management
by Giuseppe Angellotti, Denise Murgia, Giuseppina Campisi and Viviana De Caro
Biomedicines 2020, 8(11), 504; https://doi.org/10.3390/biomedicines8110504 - 16 Nov 2020
Cited by 14 | Viewed by 3992
Abstract
The restoration and prosthetic rehabilitation of missing teeth are commonly performed using dental implants, which are extremely effective and long-lasting techniques due to their osteointegration ability with the preimplant tissues. Quercetin is a phytoestrogen-like flavonoid well known for its several positive effects on [...] Read more.
The restoration and prosthetic rehabilitation of missing teeth are commonly performed using dental implants, which are extremely effective and long-lasting techniques due to their osteointegration ability with the preimplant tissues. Quercetin is a phytoestrogen-like flavonoid well known for its several positive effects on human health, mostly linked to the anti-inflammatory, antioxidant, and antibacterial activities against both Gram-positive and Gram-negative bacteria. Moreover, many studies in dentistry and the maxillofacial fields have highlighted the positive effects of quercetin on osteogenesis, acting on osteoblast activity and angiogenetic process, and promoting soft and hard tissue regeneration. This review focuses on the role of quercetin on the healing and restoration of bony defects, considering the experimental findings of its application both in vitro and in vivo as a mere compound or in association with scaffolds and dental implants having functionalized surfaces. Full article
(This article belongs to the Special Issue Soft and Hard Tissue Regeneration)
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Graphical abstract

28 pages, 1237 KiB  
Review
Bioengineered Skin Intended as In Vitro Model for Pharmacosmetics, Skin Disease Study and Environmental Skin Impact Analysis
by Raquel Sanabria-de la Torre, Ana Fernández-González, María I. Quiñones-Vico, Trinidad Montero-Vilchez and Salvador Arias-Santiago
Biomedicines 2020, 8(11), 464; https://doi.org/10.3390/biomedicines8110464 - 31 Oct 2020
Cited by 19 | Viewed by 5447
Abstract
This review aims to be an update of Bioengineered Artificial Skin Substitutes (BASS) applications. At the first moment, they were created as an attempt to replace native skin grafts transplantation. Nowadays, these in vitro models have been increasing and widening their application areas, [...] Read more.
This review aims to be an update of Bioengineered Artificial Skin Substitutes (BASS) applications. At the first moment, they were created as an attempt to replace native skin grafts transplantation. Nowadays, these in vitro models have been increasing and widening their application areas, becoming important tools for research. This study is focus on the ability to design in vitro BASS which have been demonstrated to be appropriate to develop new products in the cosmetic and pharmacology industry. Allowing to go deeper into the skin disease research, and to analyze the effects provoked by environmental stressful agents. The importance of BASS to replace animal experimentation is also highlighted. Furthermore, the BASS validation parameters approved by the OECD (Organisation for Economic Co-operation and Development) are also analyzed. This report presents an overview of the skin models applicable to skin research along with their design methods. Finally, the potential and limitations of the currently available BASS to supply the demands for disease modeling and pharmaceutical screening are discussed. Full article
(This article belongs to the Special Issue Soft and Hard Tissue Regeneration)
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20 pages, 973 KiB  
Review
Bioabsorbable Osteofixation Materials for Maxillofacial Bone Surgery: A Review on Polymers and Magnesium-Based Materials
by Sung-Woon On, Seoung-Won Cho, Soo-Hwan Byun and Byoung-Eun Yang
Biomedicines 2020, 8(9), 300; https://doi.org/10.3390/biomedicines8090300 - 21 Aug 2020
Cited by 48 | Viewed by 6136
Abstract
Clinical application of osteofixation materials is essential in performing maxillofacial surgeries requiring rigid fixation of bone such as trauma surgery, orthognathic surgery, and skeletal reconstruction. In addition to the use of titanium plates and screws, clinical applications and attempts using bioabsorbable materials for [...] Read more.
Clinical application of osteofixation materials is essential in performing maxillofacial surgeries requiring rigid fixation of bone such as trauma surgery, orthognathic surgery, and skeletal reconstruction. In addition to the use of titanium plates and screws, clinical applications and attempts using bioabsorbable materials for osteofixation surgery are increasing with demands to avoid secondary surgery for the removal of plates and screws. Synthetic polymeric plates and screws were developed, reaching satisfactory physical properties comparable to those made with titanium. Although these polymeric materials are actively used in clinical practice, there remain some limitations to be improved. Due to questionable physical strength and cumbersome molding procedures, interests in resorbable metal materials for osteofixation emerged. Magnesium (Mg) gained attention again in the last decade as a new metallic alternative, and numerous animal studies to evaluate the possibility of clinical application of Mg-based materials are being conducted. Thanks to these researches and studies, vascular application of Mg-based biomaterials was successful; however, further studies are required for the clinical application of Mg-based biomaterials for osteofixation, especially in the facial skeleton. The review provides an overview of bioabsorbable osteofixation materials in maxillofacial bone surgery from polymer to Mg. Full article
(This article belongs to the Special Issue Soft and Hard Tissue Regeneration)
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