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Biocompatible and Biodegradable 3D Scaffolds

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A special issue of Materials (ISSN 1996-1944). This special issue belongs to the section "Biomaterials".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 29123

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Dr. Adriana Kovalcik

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Faculty of Chemistry, Brno University of Technology, Purkynova 118, 612 00 Brno, Czech Republic
Interests: polyhydroxyalkanoates; polylactide; lignin; biocomposites; modification
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Dear Colleagues,

Tissue engineering intends to develop "neo-tissues" with a chemical nature, morphology, and 3D structure that would encourage infiltration, adhesion, proliferation and cell growth during tissue regeneration or formation. A few technologies have been developed for the processing of scaffolds such as freeze drying, gas foaming, porogen leaching, polymerization-induced phase separation, electrospinning and additive rapid prototyping (e.g., fused deposition modeling, selective laser sintering, and micro-stereolithography). On the one hand, the artificial 3D scaffolds should fulfill demands on precise geometry and morphology (micro- and macro-structures) as well as showing sufficient mechanical stability. On the other hand, they should be non-toxic, nonantigenic, noncarcinogenic, nonteratogenic and biocompatible. Recently, biodegradability has also been marked as a required parameter.

Tissue engineering is a relatively new and rapidly advancing interdisciplinary field of biomedical research that combines knowledge from the biological sciences, polymer chemistry, material engineering, and computer sciences. It is my privilege to invite you to submit a manuscript for the upcoming Special Issue of Materials (ISSN 1996-1944), entitled “Biocompatible and biodegradable 3D scaffolds”. Full papers, review articles and short communications from the area of tissue engineering focused on the development of biodegradable and biocompatible materials for 3D scaffolds are welcome. The knowledge and results from high-quality and original research aimed at the synthesis/production of biodegradable materials (including biopolymers, synthetic polymers, copolymers, blends, and composites) that remain stable under certain biomechanical conditions, for a particular time, and that degrade at a controlled rate will be highly supported. However, works with a focus on testing and processing methods or strategies, promoting the construction of 3D scaffolds with a sufficient structure and mechanical properties are expected and will receive special attention.

Assoc. Prof. Adriana Kovalcik
Guest Editor

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Keywords

Additive rapid prototyping
3D scaffolds
Biocompatibility
Biodegradable polymers
Biodegradation
Cell adhesion
Electrospinning
Proliferation
Surface properties
Tissue engineering

Published Papers (9 papers)

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Research

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16 pages, 4077 KiB

Open AccessArticle

Warp-Knitted Spacer Fabrics: A Versatile Platform to Generate Fiber-Reinforced Hydrogels for 3D Tissue Engineering

by Benedikt Schäfer, Caroline Emonts, Nikola Glimpel, Tim Ruhl, Astrid S. Obrecht, Stefan Jockenhoevel, Thomas Gries, Justus P. Beier and Andreas Blaeser

Materials 2020, 13(16), 3518; https://doi.org/10.3390/ma13163518 - 10 Aug 2020

Cited by 10 | Viewed by 3946

Abstract

Mesenchymal stem cells (MSCs) possess huge potential for regenerative medicine. For tissue engineering approaches, scaffolds and hydrogels are routinely used as extracellular matrix (ECM) carriers. The present study investigated the feasibility of using textile-reinforced hydrogels with adjustable porosity and elasticity as a versatile platform for soft tissue engineering. A warp-knitted poly (ethylene terephthalate) (PET) scaffold was developed and characterized with respect to morphology, porosity, and mechanics. The textile carrier was infiltrated with hydrogels and cells resulting in a fiber-reinforced matrix with adjustable biological as well as mechanical cues. Finally, the potential of this platform technology for regenerative medicine was tested on the example of fat tissue engineering. MSCs were seeded on the construct and exposed to adipogenic differentiation medium. Cell invasion was detected by two-photon microscopy, proliferation was measured by the PrestoBlue assay. Successful adipogenesis was demonstrated using Oil Red O staining as well as measurement of secreted adipokines. In conclusion, the given microenvironment featured optimal mechanical as well as biological properties for proliferation and differentiation of MSCs. Besides fat tissue, the textile-reinforced hydrogel system with adjustable mechanics could be a promising platform for future fabrication of versatile soft tissues, such as cartilage, tendon, or muscle. Full article

(This article belongs to the Special Issue Biocompatible and Biodegradable 3D Scaffolds)

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17 pages, 8456 KiB

Open AccessArticle

Xeno-Free In Vitro Cultivation and Osteogenic Differentiation of hAD-MSCs on Resorbable 3D Printed RESOMER^®

by Marline Kirsch, Annabelle-Christin Herder, Cécile Boudot, Andreas Karau, Jessica Rach, Wiebke Handke, Axel Seltsam, Thomas Scheper and Antonina Lavrentieva

Materials 2020, 13(15), 3399; https://doi.org/10.3390/ma13153399 - 31 Jul 2020

Cited by 3 | Viewed by 2670

Abstract

The development of alloplastic resorbable materials can revolutionize the field of implantation technology in regenerative medicine. Additional opportunities to colonize the three-dimensionally (3D) printed constructs with the patient’s own cells prior to implantation can improve the regeneration process but requires optimization of cultivation protocols. Human platelet lysate (hPL) has already proven to be a suitable replacement for fetal calf serum (FCS) in 2D and 3D cell cultures. In this study, we investigated the in vitro biocompatibility of the printed RESOMER^® Filament LG D1.75 materials as well as the osteogenic differentiation of human mesenchymal stem cells (hMSCs) cultivated on 3D printed constructs under the influence of different medium supplements (FCS, human serum (HS) and hPL). Additionally, the in vitro degradation of the material was studied over six months. We demonstrated that LG D1.75 is biocompatible and has no in vitro cytotoxic effects on hMSCs. Furthermore, hMSCs grown on the constructs could be differentiated into osteoblasts, especially supported by supplementation with hPL. Over six months under physiological in vitro conditions, a distinct degradation was observed, which, however, had no influence on the biocompatibility of the material. Thus, the overall suitability of the material LG D1.75 to produce 3D printed, resorbable bone implants and the promising use of hPL in the xeno-free cultivation of human MSCs on such implants for autologous transplantation have been demonstrated. Full article

(This article belongs to the Special Issue Biocompatible and Biodegradable 3D Scaffolds)

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21 pages, 3418 KiB

Open AccessArticle

Enzymatic Hydrolysis of Poly(3-Hydroxybutyrate-co-3-Hydroxyvalerate) Scaffolds

by Adriana Kovalcik, Stanislav Obruca, Michal Kalina, Michal Machovsky, Vojtech Enev, Michaela Jakesova, Marketa Sobkova and Ivana Marova

Materials 2020, 13(13), 2992; https://doi.org/10.3390/ma13132992 - 5 Jul 2020

Cited by 17 | Viewed by 2582

Abstract

Polyhydroxyalkanoates (PHAs) are hydrolyzable bio-polyesters. The possibility of utilizing lignocellulosic waste by-products and grape pomace as carbon sources for PHA biosynthesis was investigated. PHAs were biosynthesized by employing Cupriavidus necator grown on fructose (PHBV-1) or grape sugar extract (PHBV-2). Fifty grams of lyophilized grape sugar extract contained 19.2 g of glucose, 19.1 g of fructose, 2.7 g of pectin, 0.52 g of polyphenols, 0.51 g of flavonoids and 7.97 g of non-identified rest compounds. The grape sugar extract supported the higher production of biomass and modified the composition of PHBV-2. The biosynthesized PHAs served as matrices for the preparation of the scaffolds. The PHBV-2 scaffolds had about 44.2% lower crystallinity compared to the PHBV-1 scaffolds. The degree of crystallinity markedly influenced the mechanical behavior and enzymatic hydrolysis of the PHA scaffolds in the synthetic gastric juice and phosphate buffer saline solution with the lipase for 81 days. The higher proportion of amorphous moieties in PHBV-2 accelerated enzymatic hydrolysis. After 81-days of lasting enzymatic hydrolysis, the morphological changes of the PHBV-1 scaffolds were negligible compared to the visible destruction of the PHBV-2 scaffolds. These results indicated that the presence of pectin and phenolic moieties in PHBV may markedly change the semi-crystalline character of PHBV, as well as its mechanical properties and the course of abiotic or enzymatic hydrolysis. Full article

(This article belongs to the Special Issue Biocompatible and Biodegradable 3D Scaffolds)

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14 pages, 3310 KiB

Open AccessArticle

Effects of Cryopreservation on Cell Metabolic Activity and Function of Biofabricated Structures Laden with Osteoblasts

by Laura G. Hernández-Tapia, Zdenka Fohlerová, Jan Žídek, Marco A. Alvarez-Perez, Ladislav Čelko, Jozef Kaiser and Edgar B. Montufar

Materials 2020, 13(8), 1966; https://doi.org/10.3390/ma13081966 - 22 Apr 2020

Cited by 11 | Viewed by 2791

Abstract

Biofabrication and maturation of bone constructs is a long-term task that requires a high degree of specialization. This specialization falls onto the hierarchy complexity of the bone tissue that limits the transfer of this technology to the clinic. This work studied the effects of the short-term cryopreservation on biofabricated osteoblast-containing structures, with the final aim to make them steadily available in biobanks. The biological responses studied include the osteoblast post-thawing metabolic activity and the recovery of the osteoblastic function of 3D-bioprinted osteoblastic structures and beta tricalcium phosphate (β-TCP) scaffolds infiltrated with osteoblasts encapsulated in a hydrogel. The obtained structures were cryopreserved at −80 °C for 7 days using dimethyl sulfoxide (DMSO) as cryoprotectant additive. After thawing the structures were cultured up to 14 days. The results revealed fundamental biological aspects for the successful cryopreservation of osteoblast constructs. In summary, immature osteoblasts take longer to recover than mature osteoblasts. The pre-cryopreservation culture period had an important effect on the metabolic activity and function maintain, faster recovering normal values when cryopreserved after longer-term culture (7 days). The use of β-TCP scaffolds further improved the osteoblast survival after cryopreservation, resulting in similar levels of alkaline phosphatase activity in comparison with the non-preserved structures. These results contribute to the understanding of the biology of cryopreserved osteoblast constructs, approaching biofabrication to the clinical practice. Full article

(This article belongs to the Special Issue Biocompatible and Biodegradable 3D Scaffolds)

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16 pages, 5239 KiB

Open AccessFeature PaperArticle

Exploratory Full-Field Strain Analysis of Regenerated Bone Tissue from Osteoinductive Biomaterials

by Marta Peña Fernández, Cameron Black, Jon Dawson, David Gibbs, Janos Kanczler, Richard O. C. Oreffo and Gianluca Tozzi

Materials 2020, 13(1), 168; https://doi.org/10.3390/ma13010168 - 1 Jan 2020

Cited by 13 | Viewed by 3487

Abstract

Biomaterials for bone regeneration are constantly under development, and their application in critical-sized defects represents a promising alternative to bone grafting techniques. However, the ability of all these materials to produce bone mechanically comparable with the native tissue remains unclear. This study aims to explore the full-field strain evolution in newly formed bone tissue produced in vivo by different osteoinductive strategies, including delivery systems for BMP-2 release. In situ high-resolution X-ray micro-computed tomography (microCT) and digital volume correlation (DVC) were used to qualitatively assess the micromechanics of regenerated bone tissue. Local strain in the tissue was evaluated in relation to the different bone morphometry and mineralization for specimens (n = 2 p/treatment) retrieved at a single time point (10 weeks in vivo). Results indicated a variety of load-transfer ability for the different treatments, highlighting the mechanical adaptation of bone structure in the early stages of bone healing. Although exploratory due to the limited sample size, the findings and analysis reported herein suggest how the combination of microCT and DVC can provide enhanced understanding of the micromechanics of newly formed bone produced in vivo, with the potential to inform further development of novel bone regeneration approaches. Full article

(This article belongs to the Special Issue Biocompatible and Biodegradable 3D Scaffolds)

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14 pages, 5752 KiB

Open AccessArticle

Facile Preparation of Porous Microfiber from Poly-3-(R)-Hydroxybutyrate and Its Application

by Vojtech Kundrat, Petra Matouskova and Ivana Marova

Materials 2020, 13(1), 86; https://doi.org/10.3390/ma13010086 - 23 Dec 2019

Cited by 5 | Viewed by 2283

Abstract

In this study, we described the development of a simplified wet spinning method of the production of a novel type of porous continuous fiber based on poly-3-(R)-hydroxybutyrate (PHB). The principle of this method is precipitation of PHB dissolved in chloroform solution into the ethanol precipitation bath. The influence of various PHB concentrations and feed rates on specific surface area (measured by nitrogen absorption method) was studied. Materials were also characterized by SEM. Surface areas of fibers achieved by wet spinning were in the range of tens of m².g⁻¹, and the biggest surface area value was 55 m².g^–1. The average diameter of fibers was in the range of 20–120 μm and was dependent on both PHB concentration and feed rate. Optimum conditions for reaching stable fibers of high surface area were 3–5 % w.t. of PHB and feed rate 0.5–3 ml.h⁻¹. Fibers were functionalized by adsorption of some natural plant extracts. The incorporation of active substances into fibers was confirmed by infrared spectroscopy. High antioxidant and antimicrobial effect of PHB-fibers with cloves extract was found, as well as excellent long-term stability and optimal dynamics of the release of active compounds. The newly produced material would be applicable in pharmacy, cosmetics, and wound healing. Full article

(This article belongs to the Special Issue Biocompatible and Biodegradable 3D Scaffolds)

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13 pages, 2905 KiB

Open AccessFeature PaperArticle

Drug Release Kinetics of Electrospun PHB Meshes

by Vojtech Kundrat, Nicole Cernekova, Adriana Kovalcik, Vojtech Enev and Ivana Marova

Materials 2019, 12(12), 1924; https://doi.org/10.3390/ma12121924 - 14 Jun 2019

Cited by 23 | Viewed by 3943

Abstract

Microbial poly(3-hydroxybutyrate) (PHB) has several advantages including its biocompatibility and ability to degrade in vivo and in vitro without toxic substances. This paper investigates the feasibility of electrospun PHB meshes serving as drug delivery systems. The morphology of the electrospun samples was modified by varying the concentration of PHB in solution and the solvent composition. Scanning electron microscopy of the electrospun PHB scaffolds revealed the formation of different morphologies including porous, filamentous/beaded and fiber structures. Levofloxacin was used as the model drug for incorporation into PHB electrospun meshes. The entrapment efficiency was found to be dependent on the viscosity of the PHB solution used for electrospinning and ranged from 14.4–81.8%. The incorporation of levofloxacin in electrospun meshes was confirmed by Fourier-transform infrared spectroscopy and UV-VIS spectroscopy. The effect of the morphology of the electrospun meshes on the levofloxacin release profile was screened in vitro in phosphate-buffered saline solution. Depending upon the morphology, the electrospun meshes released about 14–20% of levofloxacin during the first 24 h. The percentage of drug released after 13 days increased up to 32.4% and was similar for all tested morphologies. The antimicrobial efficiency of all tested samples independent of the morphology, was confirmed by agar diffusion testing. Full article

(This article belongs to the Special Issue Biocompatible and Biodegradable 3D Scaffolds)

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10 pages, 2160 KiB

Open AccessArticle

Charge and Peptide Concentration as Determinants of the Hydrogel Internal Aqueous Environment

by Scott V. Elgersma, Michelle Ha, Jung-Lynn Jonathan Yang, Vladimir K. Michaelis and Larry D. Unsworth

Materials 2019, 12(5), 832; https://doi.org/10.3390/ma12050832 - 12 Mar 2019

Cited by 8 | Viewed by 3627

Abstract

Self-assembling peptides are a promising class of biomaterials with desirable biocompatibility and versatility. In particular, the oligopeptide (RADA)₄, consisting of arginine (R), alanine (A), and aspartic acid (D), self-assembles into nanofibers that develop into a three-dimensional hydrogel of up to 99.5% (w/v) water; yet, the organization of water within the hydrogel matrix is poorly understood. Importantly, peptide concentration and polarity are hypothesized to control the internal water structure. Using variable temperature deuterium solid-state nuclear magnetic resonance (²H NMR) spectroscopy, we measured the amount of bound water in (RADA)₄-based hydrogels, quantified as the non-frozen water content. To investigate how peptide polarity affects water structure, five lysine (K) moieties were appended to (RADA)₄ to generate (RADA)₄K₅. Hydrogels at 1 and 5% total peptide concentration were prepared from a 75:25 (w/w) blend of (RADA)₄:(RADA)₄K₅ and similarly analyzed by ²H NMR. Interestingly, at 5% peptide concentration, there was lower mobile water content in the lysinated versus the pristine (RADA)₄ hydrogel. Regardless of the presence of lysine, the 5% peptide concentration had higher non-frozen water content at temperatures as low as 217 ± 1.0 K, suggesting that bound water increases with peptide concentration. The bound water, though non-frozen, may be strongly bound to the charged lysine moiety to appear as immobilized water. Further understanding of the factors controlling water structure within hydrogels is important for tuning the transport properties of bioactive solutes in the hydrogel matrix when designing for biomedical applications. Full article

(This article belongs to the Special Issue Biocompatible and Biodegradable 3D Scaffolds)

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Review

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11 pages, 227 KiB

Open AccessFeature PaperReview

Cell-Free Scaffolds as a Monotherapy for Focal Chondral Knee Defects

by Haowen Kwan, Emanuele Chisari and Wasim S. Khan

Materials 2020, 13(2), 306; https://doi.org/10.3390/ma13020306 - 9 Jan 2020

Cited by 22 | Viewed by 3027

Abstract

Chondral knee defects have a limited ability to be repaired. Current surgical interventions have been unable to regenerate articular cartilage with the mechanical properties of native hyaline cartilage. The use of a scaffold-based approach is a potential solution. Scaffolds are often implanted with cells to stimulate cartilage regeneration, but cell-based therapies are associated with additional regulatory restrictions, an additional surgical procedure for cell harvest, time for cell expansion, and the associated costs. To overcome these disadvantages, cell-free scaffolds can be used in isolation allowing native cells to attach over time. This review discusses the optimal properties of scaffolds used for chondral defects, and the evidence for the use of hydrogel scaffolds and hydrogel–synthetic polymer hybrid scaffolds. Preclinical and clinical studies have shown that cell-free scaffolds can support articular cartilage regeneration and have the potential to treat chondral defects. However, there are very few studies in this area and, despite the many biomaterials tested in cell-based scaffolds, most cell-free studies focused on a specific type I collagen scaffold. Future studies on cell-free scaffolds should adopt the modifications made to cell-based scaffolds and replicate them in the clinical setting. More studies are also needed to understand the underlying mechanism of cell-free scaffolds. Full article

(This article belongs to the Special Issue Biocompatible and Biodegradable 3D Scaffolds)

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