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

Deadline for manuscript submissions: closed (20 December 2015) | Viewed by 97266

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Dr. C. Edi Tanase

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Research Associate, Cambridge Centre for Medical Materials, University of Cambridge, Department of Materials Science and Metallurgy, 27 Charles Babbage Rd, Cambridge CB3 0FS, UK

Prof. Dr. Michael Nerlich

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Chair Department of Trauma Surgery, Orthopaedic Surgery, Sportsmedicine, FIFA-Medical Centre of Excellence, Regensburg University Medical Center, 93042 Regensburg, Germany

Dr. Arne Berner

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Centrum für Muskuloskeletale Chirurgie, Charité-Universitätsmedizin Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, D-13353 Berlin, Germany
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

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Keywords

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

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Published Papers (11 papers)

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Research

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15 pages, 17388 KiB

Open AccessFeature PaperArticle

Higher Ratios of Hyaluronic Acid Enhance Chondrogenic Differentiation of Human MSCs in a Hyaluronic Acid–Gelatin Composite Scaffold

by Christian G. Pfeifer, Arne Berner, Matthias Koch, Werner Krutsch, Richard Kujat, Peter Angele, Michael Nerlich and Johannes Zellner

Materials 2016, 9(5), 381; https://doi.org/10.3390/ma9050381 - 17 May 2016

Cited by 36 | Viewed by 7340

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 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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14 pages, 4327 KiB

Open AccessArticle

In Vitro Testing of Scaffolds for Mesenchymal Stem Cell-Based Meniscus Tissue Engineering—Introducing a New Biocompatibility Scoring System

by Felix P. Achatz, Richard Kujat, Christian G. Pfeifer, Matthias Koch, Michael Nerlich, Peter Angele and Johannes Zellner

Materials 2016, 9(4), 276; https://doi.org/10.3390/ma9040276 - 7 Apr 2016

Cited by 14 | Viewed by 7247

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 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)

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19 pages, 3208 KiB

Open AccessFeature PaperArticle

Microparticles for Sustained Growth Factor Delivery in the Regeneration of Critically-Sized Segmental Tibial Bone Defects

by Giles T. S. Kirby, Lisa J. White, Roland Steck, Arne Berner, Kristofor Bogoevski, Omar Qutachi, Brendan Jones, Siamak Saifzadeh, Dietmar W. Hutmacher, Kevin M. Shakesheff and Maria A. Woodruff

Materials 2016, 9(4), 259; https://doi.org/10.3390/ma9040259 - 31 Mar 2016

Cited by 26 | Viewed by 7894

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 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)

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15 pages, 4696 KiB

Open AccessArticle

Poly(ε-caprolactone) Scaffolds Fabricated by Melt Electrospinning for Bone Tissue Engineering

by Sascha Zaiss, Toby D. Brown, Johannes C. Reichert and Arne Berner

Materials 2016, 9(4), 232; https://doi.org/10.3390/ma9040232 - 25 Mar 2016

Cited by 60 | Viewed by 10557

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. 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)

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9 pages, 881 KiB

Open AccessFeature PaperArticle

Collagen Type I Conduits for the Regeneration of Nerve Defects

by Silvan Klein, Jody Vykoukal, Oliver Felthaus, Thomas Dienstknecht and Lukas Prantl

Materials 2016, 9(4), 219; https://doi.org/10.3390/ma9040219 - 23 Mar 2016

Cited by 23 | Viewed by 5285

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 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)

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9 pages, 4566 KiB

Open AccessFeature PaperArticle

Differential Effects of Coating Materials on Viability and Migration of Schwann Cells

by Silvan Klein, Lukas Prantl, Jody Vykoukal, Markus Loibl and Oliver Felthaus

Materials 2016, 9(3), 150; https://doi.org/10.3390/ma9030150 - 3 Mar 2016

Cited by 17 | Viewed by 4784

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 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)

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21 pages, 1137 KiB

Open AccessFeature PaperReview

Heterogeneity of Scaffold Biomaterials in Tissue Engineering

by Lauren Edgar, Kyle McNamara, Theresa Wong, Riccardo Tamburrini, Ravi Katari and Giuseppe Orlando

Materials 2016, 9(5), 332; https://doi.org/10.3390/ma9050332 - 3 May 2016

Cited by 76 | Viewed by 9540

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 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)

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24 pages, 645 KiB

Open AccessReview

Composite Hydrogels for Bone Regeneration

by Gianluca Tozzi, Arianna De Mori, Antero Oliveira and Marta Roldo

Materials 2016, 9(4), 267; https://doi.org/10.3390/ma9040267 - 2 Apr 2016

Cited by 132 | Viewed by 11790

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 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)

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11 pages, 580 KiB

Open AccessReview

Repopulating Decellularized Kidney Scaffolds: An Avenue for Ex Vivo Organ Generation

by Robert A. McKee and Rebecca A. Wingert

Materials 2016, 9(3), 190; https://doi.org/10.3390/ma9030190 - 11 Mar 2016

Cited by 19 | Viewed by 7488

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, 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)

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11 pages, 3587 KiB

Open AccessReview

Advanced Engineering Strategies for Periodontal Complex Regeneration

by Chan Ho Park, Kyoung-Hwa Kim, Yong-Moo Lee and Yang-Jo Seol

Materials 2016, 9(1), 57; https://doi.org/10.3390/ma9010057 - 18 Jan 2016

Cited by 42 | Viewed by 8653

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 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)

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13 pages, 2154 KiB

Open AccessReview

Mechanisms of in Vivo Degradation and Resorption of Calcium Phosphate Based Biomaterials

by Zeeshan Sheikh, Mohamed-Nur Abdallah, Ahmed Abdalla Hanafi, Syed Misbahuddin, Haroon Rashid and Michael Glogauer

Materials 2015, 8(11), 7913-7925; https://doi.org/10.3390/ma8115430 - 23 Nov 2015

Cited by 183 | Viewed by 14120

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 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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