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Special Issue "Regenerative Materials"

A special issue of Materials (ISSN 1996-1944).

Deadline for manuscript submissions: closed (20 December 2015)

Special Issue Editors

Guest Editor
Dr. C. Edi Tanase

Research Associate, Cambridge Centre for Medical Materials, University of Cambridge, Department of Materials Science and Metallurgy, 27 Charles Babbage Rd, Cambridge CB3 0FS, United Kingdom
Website | E-Mail
Phone: +44 (0)1223334560
Guest Editor
Prof. Dr. Michael Nerlich

Chair Department of Trauma Surgery, Orthopaedic Surgery, Sportsmedicine, FIFA-Medical Centre of Excellence, Regensburg University Medical Center, 93042 Regensburg, Germany
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Guest Editor
Dr. Arne Berner

Centrum für Muskuloskeletale Chirurgie, Charité-Universitätsmedizin Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, D-13353, Berlin
Website | E-Mail
Interests: Tissue engineering; regenerative materials; biomaterials; bone regeneration; bone defects

Special Issue Information

Dear Colleagues,

Regenerative Medicine is an extremely important area which has grown rapidly embracing the novel developments from engineering, life sciences, and clinical medicine. As such, regenerative medicine is an inherent field. The main focus of the “Regenerative Materials” Special Issue is to provide and comprehend important topics, such as tissue regeneration, cell biology, materials science, chemistry, and engineering, with respect to regenerative medicine. Therefore, novel developments in science and technology, with prospective application in regenerative medicine, will be addressed in this issue.
With immense pleasure, we invite you to submit a manuscript for this Special Issue. Full papers, communications, and reviews are welcome.

Dr. C. Edi Tanase
Prof. Dr. Michael Nerlich
Dr. Arne Berner
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 papers will be 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. Materials 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 1500 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.



Keywords

  • Bioactive
  • Biodegradable
  • Biomaterials
  • Biomimetic
  • Bioresorbable
  • ŸCell-material interface
  • Drug delivery systems
  • Regenerative medicine
  • Tissue regeneration
  • Tunable materials

Published Papers (11 papers)

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Research

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Open AccessFeature PaperArticle Higher Ratios of Hyaluronic Acid Enhance Chondrogenic Differentiation of Human MSCs in a Hyaluronic Acid–Gelatin Composite Scaffold
Materials 2016, 9(5), 381; doi:10.3390/ma9050381
Received: 10 March 2016 / Revised: 26 April 2016 / Accepted: 10 May 2016 / Published: 17 May 2016
Cited by 2 | PDF Full-text (17388 KB) | HTML Full-text | XML Full-text
Abstract
Mesenchymal stem cells (MSCs) seeded on specific carrier materials are a promising source for the repair of traumatic cartilage injuries. The best supportive carrier material has not yet been determined. As natural components of cartilage’s extracellular matrix, hyaluronic acid and collagen are the
[...] Read more.
Mesenchymal stem cells (MSCs) seeded on specific carrier materials are a promising source for the repair of traumatic cartilage injuries. The best supportive carrier material has not yet been determined. As natural components of cartilage’s extracellular matrix, hyaluronic acid and collagen are the focus of biomaterial research. In order to optimize chondrogenic support, we investigated three different scaffold compositions of a hyaluronic acid (HA)-gelatin based biomaterial. Methods: Human MSCs (hMSCs) were seeded under vacuum on composite scaffolds of three different HA-gelatin ratios and cultured in chondrogenic medium for 21 days. Cell-scaffold constructs were assessed at different time points for cell viability, gene expression patterns, production of cartilage-specific extracellular matrix (ECM) and for (immuno-)histological appearance. The intrinsic transforming growth factor beta (TGF-beta) uptake of empty scaffolds was evaluated by determination of the TGF-beta concentrations in the medium over time. Results: No significant differences were found for cell seeding densities and cell viability. hMSCs seeded on scaffolds with higher ratios of HA showed better cartilage-like differentiation in all evaluated parameters. TGF-beta uptake did not differ between empty scaffolds. Conclusion: Higher ratios of HA support the chondrogenic differentiation of hMSCs seeded on a HA-gelatin composite scaffold. Full article
(This article belongs to the Special Issue Regenerative Materials)
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Open AccessArticle In Vitro Testing of Scaffolds for Mesenchymal Stem Cell-Based Meniscus Tissue Engineering—Introducing a New Biocompatibility Scoring System
Materials 2016, 9(4), 276; doi:10.3390/ma9040276
Received: 30 January 2016 / Revised: 14 March 2016 / Accepted: 29 March 2016 / Published: 7 April 2016
Cited by 1 | PDF Full-text (4327 KB) | HTML Full-text | XML Full-text
Abstract
A combination of mesenchymal stem cells (MSCs) and scaffolds seems to be a promising approach for meniscus repair. To facilitate the search for an appropriate scaffold material a reliable and objective in vitro testing system is essential. This paper introduces a new scoring
[...] Read more.
A combination of mesenchymal stem cells (MSCs) and scaffolds seems to be a promising approach for meniscus repair. To facilitate the search for an appropriate scaffold material a reliable and objective in vitro testing system is essential. This paper introduces a new scoring for this purpose and analyzes a hyaluronic acid (HA) gelatin composite scaffold and a polyurethane scaffold in combination with MSCs for tissue engineering of meniscus. The pore quality and interconnectivity of pores of a HA gelatin composite scaffold and a polyurethane scaffold were analyzed by surface photography and Berliner-Blau-BSA-solution vacuum filling. Further the two scaffold materials were vacuum-filled with human MSCs and analyzed by histology and immunohistochemistry after 21 days in chondrogenic media to determine cell distribution and cell survival as well as proteoglycan production, collagen type I and II content. The polyurethane scaffold showed better results than the hyaluronic acid gelatin composite scaffold, with signs of central necrosis in the HA gelatin composite scaffolds. The polyurethane scaffold showed good porosity, excellent pore interconnectivity, good cell distribution and cell survival, as well as an extensive content of proteoglycans and collagen type II. The polyurethane scaffold seems to be a promising biomaterial for a mesenchymal stem cell-based tissue engineering approach for meniscal repair. The new score could be applied as a new standard for in vitro scaffold testing. Full article
(This article belongs to the Special Issue Regenerative Materials)
Open AccessFeature PaperArticle Microparticles for Sustained Growth Factor Delivery in the Regeneration of Critically-Sized Segmental Tibial Bone Defects
Materials 2016, 9(4), 259; doi:10.3390/ma9040259
Received: 18 January 2016 / Revised: 18 March 2016 / Accepted: 18 March 2016 / Published: 31 March 2016
Cited by 2 | PDF Full-text (3208 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
This study trialled the controlled delivery of growth factors within a biodegradable scaffold in a large segmental bone defect model. We hypothesised that co-delivery of vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) followed by bone morphogenetic protein-2 (BMP-2) could
[...] Read more.
This study trialled the controlled delivery of growth factors within a biodegradable scaffold in a large segmental bone defect model. We hypothesised that co-delivery of vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) followed by bone morphogenetic protein-2 (BMP-2) could be more effective in stimulating bone repair than the delivery of BMP-2 alone. Poly(lactic-co-glycolic acid) (PLGA ) based microparticles were used as a delivery system to achieve a controlled release of growth factors within a medical-grade Polycaprolactone (PCL) scaffold. The scaffolds were assessed in a well-established preclinical ovine tibial segmental defect measuring 3 cm. After six months, mechanical properties and bone tissue regeneration were assessed. Mineralised bone bridging of the defect was enhanced in growth factor treated groups. The inclusion of VEGF and PDGF (with BMP-2) had no significant effect on the amount of bone regeneration at the six-month time point in comparison to BMP-2 alone. However, regions treated with VEGF and PDGF showed increased vascularity. This study demonstrates an effective method for the controlled delivery of therapeutic growth factors in vivo, using microparticles. Full article
(This article belongs to the Special Issue Regenerative Materials)
Open AccessArticle Poly(ε-caprolactone) Scaffolds Fabricated by Melt Electrospinning for Bone Tissue Engineering
Materials 2016, 9(4), 232; doi:10.3390/ma9040232
Received: 23 January 2016 / Revised: 6 March 2016 / Accepted: 17 March 2016 / Published: 25 March 2016
Cited by 6 | PDF Full-text (4696 KB) | HTML Full-text | XML Full-text
Abstract
Melt electrospinning is a promising approach to manufacture biocompatible scaffolds for tissue engineering. In this study, melt electrospinning of poly(ε-caprolactone) onto structured, metallic collectors resulted in scaffolds with an average pore size of 250–300 μm and an average fibre diameter of 15 μm.
[...] Read more.
Melt electrospinning is a promising approach to manufacture biocompatible scaffolds for tissue engineering. In this study, melt electrospinning of poly(ε-caprolactone) onto structured, metallic collectors resulted in scaffolds with an average pore size of 250–300 μm and an average fibre diameter of 15 μm. Scaffolds were seeded with ovine osteoblasts in vitro. Cell proliferation and deposition of mineralised extracellular matrix was assessed using PicoGreen® (Thermo Fisher Scientific, Scoresby, Australia) and WAKO® HR II (WAKO, Osaka, Japan) calcium assays. Biocompatibility, cell infiltration and the growth pattern of osteoblasts on scaffolds was investigated using confocal microscopy and scanning electron microscopy. Osteoblasts proliferated on the scaffolds over an entire 40-day culture period, with excellent survival rates and deposited mineralized extracellular matrix. In general, the 3D environment of the structured melt electrospun scaffold was favourable for osteoblast cultures. Full article
(This article belongs to the Special Issue Regenerative Materials)
Open AccessFeature PaperArticle Collagen Type I Conduits for the Regeneration of Nerve Defects
Materials 2016, 9(4), 219; doi:10.3390/ma9040219
Received: 24 January 2016 / Revised: 6 March 2016 / Accepted: 14 March 2016 / Published: 23 March 2016
Cited by 1 | PDF Full-text (881 KB) | HTML Full-text | XML Full-text
Abstract
To date, reliable data to support the general use of biodegradable materials for bridging nerve defects are still scarce. We present the outcome of nerve regeneration following type I collagen conduit nerve repair in patients with large-diameter nerve gaps. Ten patients underwent nerve
[...] Read more.
To date, reliable data to support the general use of biodegradable materials for bridging nerve defects are still scarce. We present the outcome of nerve regeneration following type I collagen conduit nerve repair in patients with large-diameter nerve gaps. Ten patients underwent nerve repair using a type I collagen nerve conduit. Patients were re-examined at a minimal follow-up of 14.0 months and a mean follow-up of 19.9 months. Regeneration of nerve tissue within the conduits was assessed by nerve conduction velocity (NCV), a static two-point discrimination (S2PD) test, and as disability of arm shoulder and hand (DASH) outcome measure scoring. Quality of life measures including patients’ perceived satisfaction and residual pain were evaluated using a visual analog scale (VAS). No implant-related complications were observed. Seven out of 10 patients reported being free of pain, and the mean VAS was 1.1. The mean DASH score was 17.0. The S2PD was below 6 mm in 40%, between 6 and 10 mm in another 40% and above 10 mm in 20% of the patients. Eight out of 10 patients were satisfied with the procedure and would undergo surgery again. Early treatment correlated with lower DASH score levels. The use of type I collagen in large-diameter gaps in young patients and early treatment presented superior functional outcomes. Full article
(This article belongs to the Special Issue Regenerative Materials)
Open AccessFeature PaperArticle Differential Effects of Coating Materials on Viability and Migration of Schwann Cells
Materials 2016, 9(3), 150; doi:10.3390/ma9030150
Received: 20 December 2015 / Revised: 19 February 2016 / Accepted: 24 February 2016 / Published: 3 March 2016
PDF Full-text (4566 KB) | HTML Full-text | XML Full-text
Abstract
Synthetic nerve conduits have emerged as an alternative to guide axonal regeneration in peripheral nerve gap injuries. Migration of Schwann cells (SC) from nerve stumps has been demonstrated as one essential factor for nerve regeneration in nerve defects. In this experiment, SC viability
[...] Read more.
Synthetic nerve conduits have emerged as an alternative to guide axonal regeneration in peripheral nerve gap injuries. Migration of Schwann cells (SC) from nerve stumps has been demonstrated as one essential factor for nerve regeneration in nerve defects. In this experiment, SC viability and migration were investigated for various materials to determine the optimal conditions for nerve regeneration. Cell viability and SC migration assays were conducted for collagen I, laminin, fibronectin, lysine and ornithine. The highest values for cell viability were detected for collagen I, whereas fibronectin was most stimulatory for SC migration. At this time, clinically approved conduits are based on single-material structures. In contrast, the results of this experiment suggest that material compounds such as collagen I in conjunction with fibronectin should be considered for optimal nerve healing. Full article
(This article belongs to the Special Issue Regenerative Materials)

Review

Jump to: Research

Open AccessFeature PaperReview Heterogeneity of Scaffold Biomaterials in Tissue Engineering
Materials 2016, 9(5), 332; doi:10.3390/ma9050332
Received: 13 March 2016 / Revised: 23 April 2016 / Accepted: 26 April 2016 / Published: 3 May 2016
Cited by 3 | PDF Full-text (1137 KB) | HTML Full-text | XML Full-text
Abstract
Tissue engineering (TE) offers a potential solution for the shortage of transplantable organs and the need for novel methods of tissue repair. Methods of TE have advanced significantly in recent years, but there are challenges to using engineered tissues and organs including but
[...] Read more.
Tissue engineering (TE) offers a potential solution for the shortage of transplantable organs and the need for novel methods of tissue repair. Methods of TE have advanced significantly in recent years, but there are challenges to using engineered tissues and organs including but not limited to: biocompatibility, immunogenicity, biodegradation, and toxicity. Analysis of biomaterials used as scaffolds may, however, elucidate how TE can be enhanced. Ideally, biomaterials should closely mimic the characteristics of desired organ, their function and their in vivo environments. A review of biomaterials used in TE highlighted natural polymers, synthetic polymers, and decellularized organs as sources of scaffolding. Studies of discarded organs supported that decellularization offers a remedy to reducing waste of donor organs, but does not yet provide an effective solution to organ demand because it has shown varied success in vivo depending on organ complexity and physiological requirements. Review of polymer-based scaffolds revealed that a composite scaffold formed by copolymerization is more effective than single polymer scaffolds because it allows copolymers to offset disadvantages a single polymer may possess. Selection of biomaterials for use in TE is essential for transplant success. There is not, however, a singular biomaterial that is universally optimal. Full article
(This article belongs to the Special Issue Regenerative Materials)
Open AccessReview Composite Hydrogels for Bone Regeneration
Materials 2016, 9(4), 267; doi:10.3390/ma9040267
Received: 2 February 2016 / Revised: 14 March 2016 / Accepted: 29 March 2016 / Published: 2 April 2016
Cited by 4 | PDF Full-text (645 KB) | HTML Full-text | XML Full-text
Abstract
Over the past few decades, bone related disorders have constantly increased. Among all pathological conditions, osteoporosis is one of the most common and often leads to bone fractures. This is a massive burden and it affects an estimated 3 million people only in
[...] Read more.
Over the past few decades, bone related disorders have constantly increased. Among all pathological conditions, osteoporosis is one of the most common and often leads to bone fractures. This is a massive burden and it affects an estimated 3 million people only in the UK. Furthermore, as the population ages, numbers are due to increase. In this context, novel biomaterials for bone fracture regeneration are constantly under development. Typically, these materials aim at favoring optimal bone integration in the scaffold, up to complete bone regeneration; this approach to regenerative medicine is also known as tissue engineering (TE). Hydrogels are among the most promising biomaterials in TE applications: they are very flexible materials that allow a number of different properties to be targeted for different applications, through appropriate chemical modifications. The present review will focus on the strategies that have been developed for formulating hydrogels with ideal properties for bone regeneration applications. In particular, aspects related to the improvement of hydrogels’ mechanical competence, controlled delivery of drugs and growth factors are treated in detail. It is hoped that this review can provide an exhaustive compendium of the main aspects in hydrogel related research and, therefore, stimulate future biomaterial development and applications. Full article
(This article belongs to the Special Issue Regenerative Materials)
Open AccessReview Repopulating Decellularized Kidney Scaffolds: An Avenue for Ex Vivo Organ Generation
Materials 2016, 9(3), 190; doi:10.3390/ma9030190
Received: 15 December 2015 / Revised: 1 March 2016 / Accepted: 4 March 2016 / Published: 11 March 2016
Cited by 2 | PDF Full-text (580 KB) | HTML Full-text | XML Full-text
Abstract
Recent research has shown that fully developed organs can be decellularized, resulting in a complex scaffold and extracellular matrix (ECM) network capable of being populated with other cells. This work has resulted in a growing field in bioengineering focused on the isolation, characterization,
[...] Read more.
Recent research has shown that fully developed organs can be decellularized, resulting in a complex scaffold and extracellular matrix (ECM) network capable of being populated with other cells. This work has resulted in a growing field in bioengineering focused on the isolation, characterization, and modification of organ derived acellular scaffolds and their potential to sustain and interact with new cell populations, a process termed reseeding. In this review, we cover contemporary advancements in the bioengineering of kidney scaffolds including novel work showing that reseeded donor scaffolds can be transplanted and can function in recipients using animal models. Several major areas of the field are taken into consideration, including the decellularization process, characterization of acellular and reseeded scaffolds, culture conditions, and cell sources. Finally, we discuss future avenues based on the advent of 3D bioprinting and recent developments in kidney organoid cultures as well as animal models of renal genesis. The ongoing mergers and collaborations between these fields hold the potential to produce functional kidneys that can be generated ex vivo and utilized for kidney transplantations in patients suffering with renal disease. Full article
(This article belongs to the Special Issue Regenerative Materials)
Open AccessReview Advanced Engineering Strategies for Periodontal Complex Regeneration
Materials 2016, 9(1), 57; doi:10.3390/ma9010057
Received: 16 December 2015 / Revised: 7 January 2016 / Accepted: 8 January 2016 / Published: 18 January 2016
Cited by 2 | PDF Full-text (3587 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The regeneration and integration of multiple tissue types is critical for efforts to restore the function of musculoskeletal complex. In particular, the neogenesis of periodontal constructs for systematic tooth-supporting functions is a current challenge due to micron-scaled tissue compartmentalization, oblique/perpendicular orientations of fibrous
[...] Read more.
The regeneration and integration of multiple tissue types is critical for efforts to restore the function of musculoskeletal complex. In particular, the neogenesis of periodontal constructs for systematic tooth-supporting functions is a current challenge due to micron-scaled tissue compartmentalization, oblique/perpendicular orientations of fibrous connective tissues to the tooth root surface and the orchestration of multiple regenerated tissues. Although there have been various biological and biochemical achievements, periodontal tissue regeneration remains limited and unpredictable. The purpose of this paper is to discuss current advanced engineering approaches for periodontal complex formations; computer-designed, customized scaffolding architectures; cell sheet technology-based multi-phasic approaches; and patient-specific constructs using bioresorbable polymeric material and 3-D printing technology for clinical application. The review covers various advanced technologies for periodontal complex regeneration and state-of-the-art therapeutic avenues in periodontal tissue engineering. Full article
(This article belongs to the Special Issue Regenerative Materials)
Open AccessReview Mechanisms of in Vivo Degradation and Resorption of Calcium Phosphate Based Biomaterials
Materials 2015, 8(11), 7913-7925; doi:10.3390/ma8115430
Received: 14 October 2015 / Revised: 9 November 2015 / Accepted: 13 November 2015 / Published: 23 November 2015
Cited by 16 | PDF Full-text (2154 KB) | HTML Full-text | XML Full-text
Abstract
Calcium phosphate ceramic materials are extensively used for bone replacement and regeneration in orthopedic, dental, and maxillofacial surgical applications. In order for these biomaterials to work effectively it is imperative that they undergo the process of degradation and resorption in vivo. This
[...] Read more.
Calcium phosphate ceramic materials are extensively used for bone replacement and regeneration in orthopedic, dental, and maxillofacial surgical applications. In order for these biomaterials to work effectively it is imperative that they undergo the process of degradation and resorption in vivo. This allows for the space to be created for the new bone tissue to form and infiltrate within the implanted graft material. Several factors affect the biodegradation and resorption of calcium phosphate materials after implantation. Various cell types are involved in the degradation process by phagocytic mechanisms (monocytes/macrophages, fibroblasts, osteoblasts) or via an acidic mechanism to reduce the micro-environmental pH which results in demineralization of the cement matrix and resorption via osteoclasts. These cells exert their degradation effects directly or indirectly through the cytokine growth factor secretion and their sensitivity and response to these biomolecules. This article discusses the mechanisms of calcium phosphate material degradation in vivo. Full article
(This article belongs to the Special Issue Regenerative Materials)
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