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Materials and Technology for Regenerative Medicine

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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 (15 November 2021) | Viewed by 21986

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Dr. Ewa Stodolak-Zych

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Department of Biomaterials and Composites, Faculty of Materials Science and Ceramics, AGH University of Science and Technology, 30-059 Krakow, Poland
Interests: porous and nonporous materials supported regenerative process: polymer nanocomposites; fibrous materials; polymer membrane; cells–materials interaction
Special Issues, Collections and Topics in MDPI journals

Dr. Maciej Boguń

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Guest Editor

Łukasiewicz Research Network - Textile Research Institute, 92-103 Łódź, Poland
Interests: woven and unwoven materials; electrospinning; melt blown techniques; biomaterials; standard tests; biomedical application

Special Issue Information

Dear Colleagues,

The idea of regenerative medicine requires the conscious use of biological, medical, and material techniques aimed at repairing and restoring normal function of damaged cells or organs, preferably at the site of destruction (in situ). Currently used regenerative medicine strategies are mainly based on induced autoregeneration, somatic cell therapy, and tissue engineering (TE). Wherever there is a need to restore large defects (i.e., critical defects) or to introduce an induced response from the body (induced autoregeneration), biomaterials are used.

Biomaterials applied in the context of regenerative medicine play the role of an active agent in the regenerative process, which is intended to facilitate, imitate, and/or reinforce the biological processes involved. The essential role of biomaterial during the regeneration of the damage may be limited to a synthetic imitation of an extracellular matrix (ECM). This approach has provided an insight into the role and function of progenitor cells and stem cells. Biomimetic materials inspired by nature are intended to reproduce the natural tissue environment on both structural and functional levels. The success of self-regenerative strategies depends equally on the predictability of the material's in vivo behavior. The substrate is expected to perform its function in a predetermined way and then degrade (not only in uncontrolled hydrolysis), e.g., in response to local changes and regeneration or colonization with native ECM cells.

Successful treatment supported with the use of biomaterials cannot exist without technologies that facilitate the forming of biomimetic supports, which stimulate regenerative processes. Most of the techniques used for regenerative medicine are traditional ones, e.g., used in the textile industry, polymer processing or ceramics technology. Among them, there are new methods allowing to obtain nanocomposites or those with highly specialized surface properties which favor adhesion or proliferation of a specific group of cells (important for the damaged site). These techniques allow obtaining substrates in the form of both 2D and 3D structures. This increases the chances of clinical application of biomaterials, although these will only be possible if not only the characteristics of the material and its safety (including the sterilization technique) are known, but also repeatability is ensured using the suitable technology.

Dr. Ewa Stodolak-Zych
Dr. Maciej Boguń
Guest Editors

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Keywords

biomimetic materials
scaffold
2D and 3D biomaterials
bioactivity
(nano)composite materials
fibrous materials
porous materials
polymer processing
ceramic technology
cells-materials interaction
(bio)degradation
regenerative process

Published Papers (7 papers)

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Research

19 pages, 3920 KiB

Open AccessArticle

Chemical Modification as a Method of Improving Biocompatibility of Carbon Nonwovens

by Justyna Frączyk, Sylwia Magdziarz, Ewa Stodolak-Zych, Ewa Dzierzkowska, Dorota Puchowicz, Irena Kamińska, Małgorzata Giełdowska and Maciej Boguń

Materials 2021, 14(12), 3198; https://doi.org/10.3390/ma14123198 - 10 Jun 2021

Cited by 5 | Viewed by 1979

Abstract

It was shown that carbon nonwoven fabrics obtained from polyacrylonitrile fibers (PAN) by thermal conversion may be modified on the surface in order to improve their biological compatibility and cellular response, which is particularly important in the regeneration of bone or cartilage tissue. Surface functionalization of carbon nonwovens containing C–C double bonds was carried out using in situ generated diazonium salts derived from aromatic amines containing both electron-acceptor and electron-donor substituents. It was shown that the modification method characteristic for materials containing aromatic structures may be successfully applied to the functionalization of carbon materials. The effectiveness of the surface modification of carbon nonwoven fabrics was confirmed by the FTIR method using an ATR device. The proposed approach allows the incorporation of various functional groups on the nonwovens’ surface, which affects the morphology of fibers as well as their physicochemical properties (wettability). The introduction of a carboxyl group on the surface of nonwoven fabrics, in a reaction with 4-aminobenzoic acid, became a starting point for further modifications necessary for the attachment of RGD-type peptides facilitating cell adhesion to the surface of materials. The surface modification reduced the wettability (θ) of the carbon nonwoven by about 50%. The surface free energy (SFE) in the chemically modified and reference nonwovens remained similar, with the surface modification causing an increase in the polar component (ɣ_p). The modification of the fiber surface was heterogeneous in nature; however, it provided an attractive site of cell–materials interaction by contacting them to the fiber surface, which supports the adhesion process. Full article

(This article belongs to the Special Issue Materials and Technology for Regenerative Medicine)

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19 pages, 10965 KiB

Open AccessArticle

GAKTpore: Stereological Characterisation Methods for Porous Foams in Biomedical Applications

by Gareth Sheppard, Karl Tassenberg, Bogdan Nenchev, Joel Strickland, Ramy Mesalam, Jennifer Shepherd and Hugo Williams

Materials 2021, 14(5), 1269; https://doi.org/10.3390/ma14051269 - 07 Mar 2021

Cited by 1 | Viewed by 2297

Abstract

In tissue engineering, scaffolds are a key component that possess a highly elaborate pore structure. Careful characterisation of such porous structures enables the prediction of a variety of large-scale biological responses. In this work, a rapid, efficient, and accurate methodology for 2D bulk porous structure analysis is proposed. The algorithm, “GAKTpore”, creates a morphology map allowing quantification and visualisation of spatial feature variation. The software achieves 99.6% and 99.1% mean accuracy for pore diameter and shape factor identification, respectively. There are two main algorithm novelties within this work: (1) feature-dependant homogeneity map; (2) a new waviness function providing insights into the convexity/concavity of pores, important for understanding the influence on cell adhesion and proliferation. The algorithm is applied to foam structures, providing a full characterisation of a 10 mm diameter SEM micrograph (14,784 × 14,915 px) with 190,249 pores in ~9 min and has elucidated new insights into collagen scaffold formation by relating microstructural formation to the bulk formation environment. This novel porosity characterisation algorithm demonstrates its versatility, where accuracy, repeatability, and time are paramount. Thus, GAKTpore offers enormous potential to optimise and enhance scaffolds within tissue engineering. Full article

(This article belongs to the Special Issue Materials and Technology for Regenerative Medicine)

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17 pages, 3540 KiB

Open AccessArticle

How Surface Properties of Silica Nanoparticles Influence Structural, Microstructural and Biological Properties of Polymer Nanocomposites

by Łukasz Zych, Anna Maria Osyczka, Agnieszka Łacz, Agnieszka Różycka, Wiktor Niemiec, Alicja Rapacz-Kmita, Ewa Dzierzkowska and Ewa Stodolak-Zych

Materials 2021, 14(4), 843; https://doi.org/10.3390/ma14040843 - 10 Feb 2021

Cited by 15 | Viewed by 1973

Abstract

The aim of this work was to study effect of the type of silica nanoparticles on the properties of nanocomposites for application in the guided bone regeneration (GBR). Two types of nanometric silica particles with different size, morphology and specific surface area (SSA) i.e., high specific surface silica (hss-SiO₂) and low specific surface silica (lss-SiO₂), were used as nano-fillers for a resorbable polymer matrix: poly(L-lactide-co-D,L-lactide), called PLDLA. It was shown that higher surface specific area and morphology (including pore size distribution) recorded for hss-SiO₂ influences chemical activity of the nanoparticle; in addition, hydroxyl groups appeared on the surface. The nanoparticle with 10 times lower specific surface area (lss-SiO₂) characterized lower chemical action. In addition, a lack of hydroxyl groups on the surface obstructed apatite nucleation (reduced zeta potential in comparison to hss-SiO₂), where an apatite layer appeared already after 48 h of incubation in the simulated body fluid (SBF), and no significant changes in crystallinity of PLDLA/lss-SiO₂ nanocomposite material in comparison to neat PLDLA foil were observed. The presence and type of inorganic particles in the PLDLA matrix influenced various physicochemical properties such as the wettability, and the roughness parameter note for PLDLA/lss-SiO₂ increased. The results of biological investigation show that the bioactive nanocomposites with hss-SiO₂ may stimulate osteoblast and fibroblast cells’proliferation and secretion of collagen type I. Additionally, both nanocomposites with the nanometric silica inducted differentiation of mesenchymal cells into osteoblasts at a proliferation stage in in vitro conditions. A higher concentration of alkaline phosphatase (ALP) was observed on the material modified with hss-SiO₂ silica. Full article

(This article belongs to the Special Issue Materials and Technology for Regenerative Medicine)

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18 pages, 1621 KiB

Open AccessArticle

Surface Modification of Biodegradable Mg-Based Scaffolds for Human Mesenchymal Stem Cell Proliferation and Osteogenic Differentiation

by Si-Han Wang, Shiao-Pieng Lee, Chung-Wei Yang and Chun-Min Lo

Materials 2021, 14(2), 441; https://doi.org/10.3390/ma14020441 - 18 Jan 2021

Cited by 7 | Viewed by 2112

Abstract

Magnesium alloys with coatings have the potential to be used for bone substitute alternatives since their mechanical properties are close to those of human bone. However, the surface modification of magnesium alloys to increase the surface biocompatibility and reduce the degradation rate remains a challenge. Here, FHA-Mg scaffolds were made of magnesium alloys and coated with fluorohydroxyapatite (FHA). Human mesenchymal stem cells (hMSCs) were cultured on FHA-Mg scaffolds and cell viability, proliferation, and osteogenic differentiation were investigated. The results showed that FHA-Mg scaffolds display a nano-scaled needle-like structure of aggregated crystallites on their surface. The average Mg²⁺ concentration in the conditioned media collected from FHA-Mg scaffolds (5.8–7.6 mM) is much lower than those collected from uncoated, Mg(OH)₂-coated, and hydroxyapatite (HA)-coated samples (32.1, 17.7, and 21.1 mM, respectively). In addition, compared with hMSCs cultured on a culture dish, cells cultured on FHA-Mg scaffolds demonstrated better proliferation and comparable osteogenic differentiation. To eliminate the effect of osteogenic induction medium, hMSCs were cultured on FHA-Mg scaffolds in culture medium and an approximate 66% increase in osteogenic differentiation was observed three weeks later, indicating a significant effect of the nanostructured surface of FHA-Mg scaffolds on hMSC behaviors. With controllable Mg²⁺ release and favorable mechanical properties, porous FHA-Mg scaffolds have a great potential in cell-based bone regeneration. Full article

(This article belongs to the Special Issue Materials and Technology for Regenerative Medicine)

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15 pages, 4309 KiB

Open AccessArticle

Comparative Study of Gelatin Hydrogels Modified by Various Cross-Linking Agents

by Joanna Skopinska-Wisniewska, Marta Tuszynska and Ewa Olewnik-Kruszkowska

Materials 2021, 14(2), 396; https://doi.org/10.3390/ma14020396 - 14 Jan 2021

Cited by 90 | Viewed by 6898

Abstract

Gelatin is a natural biopolymer derived from collagen. Due to its many advantages, such as swelling capacity, biodegradability, biocompatibility, and commercial availability, gelatin is widely used in the field of pharmacy, medicine, and the food industry. Gelatin solutions easily form hydrogels during cooling, however, the materials are mechanically poor. To improve their properties, they are often chemically crosslinked. The cross-linking agents are divided into two groups: Zero-length and non-zero-length cross-linkers. In this study, gelatin was cross-linked by three different cross-linking agents: EDC-NHS, as a typically used cross-linker, and also squaric acid (SQ) and dialdehyde starch (DAS), as representatives of a second group of cross-linkers. For all prepared gelatin hydrogels, mechanical strength tests, thermal analysis, infrared spectroscopy, swelling ability, and SEM images were performed. The results indicate that the dialdehyde starch is a better cross-linking agent for gelatin than EDC-NHS. Meanwhile, the use of squaric acid does not give beneficial changes to the properties of the hydrogel. Full article

(This article belongs to the Special Issue Materials and Technology for Regenerative Medicine)

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15 pages, 26743 KiB

Open AccessArticle

Parametric Finite Element Model and Mechanical Characterisation of Electrospun Materials for Biomedical Applications

by Katarzyna Polak-Kraśna, Emilia Mazgajczyk, Pirjo Heikkilä and Anthimos Georgiadis

Materials 2021, 14(2), 278; https://doi.org/10.3390/ma14020278 - 07 Jan 2021

Cited by 2 | Viewed by 2260

Abstract

Electrospun materials, due to their unique properties, have found many applications in the biomedical field. Exploiting their porous nanofibrous structure, they are often used as scaffolds in tissue engineering which closely resemble a native cellular environment. The structural and mechanical properties of the substrates need to be carefully optimised to mimic cues used by the extracellular matrix to guide cells’ behaviour and improve existing scaffolds. Optimisation of these parameters is enabled by using the finite element model of electrospun structures proposed in this study. First, a fully parametric three-dimensional microscopic model of electrospun material with a random fibrous network was developed. Experimental results were obtained by testing electrospun poly(ethylene) oxide materials. Parameters of single fibres were determined by atomic force microscopy nanoindentations and used as input data for the model. The validation was performed by comparing model output data with tensile test results obtained for electrospun mats. We performed extensive analysis of model parameters correlations to understand the crucial factors and enable extrapolation of a simplified model. We found good agreement between the simulation and the experimental data. The proposed model is a potent tool in the optimisation of electrospun structures and scaffolds for enhanced regenerative therapies. Full article

(This article belongs to the Special Issue Materials and Technology for Regenerative Medicine)

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16 pages, 2679 KiB

Open AccessArticle

Establishment of Collagen: Hydroxyapatite/BMP-2 Mimetic Peptide Composites

by Liane Schuster, Nina Ardjomandi, Marita Munz, Felix Umrath, Christian Klein, Frank Rupp, Siegmar Reinert and Dorothea Alexander

Materials 2020, 13(5), 1203; https://doi.org/10.3390/ma13051203 - 07 Mar 2020

Cited by 12 | Viewed by 3445

Abstract

Extensive efforts were undertaken to develop suitable biomaterials for tissue engineering (TE) applications. To facilitate clinical approval processes and ensure the success of TE applications, bioinspired concepts are currently focused on. Working on bone tissue engineering, we describe in the present study a method for biofunctionalization of collagen/hydroxyapatite composites with BMP-2 mimetic peptides. This approach is expected to be fundamentally transferable to other tissue engineering fields. A modified BMP-2 mimetic peptide containing a negatively charged poly-glutamic acid residue (E7 BMP-2 peptide) was used to bind positively charged hydroxyapatite (HA) particles by electrostatic attraction. Binding efficiency was biochemically detected to be on average 85% compared to 30% of BMP-2 peptide without E7 residue. By quartz crystal microbalance (QCM) analysis, we could demonstrate the time-dependent dissociation of the BMP-2 mimetic peptides and the stable binding of the E7 BMP-2 peptides on HA-coated quartz crystals. As shown by immunofluorescence staining, alkaline phosphatase expression is similar to that detected in jaw periosteal cells (JPCs) stimulated with the whole BMP-2 protein. Mineralization potential of JPCs in the presence of BMP-2 mimetic peptides was also shown to be at least similar or significantly higher when low peptide concentrations were used, as compared to JPCs cultured in the presence of recombinant BMP-2 controls. In the following, collagen/hydroxyapatite composite materials were prepared. By proliferation analysis, we detected a decrease in cell viability with increasing HA ratios. Therefore, we chose a collagen/hydroxyapatite ratio of 1:2, similar to the natural composition of bone. The following inclusion of E7 BMP-2 peptides within the composite material resulted in significantly elevated long-term JPC proliferation under osteogenic conditions. We conclude that our advanced approach for fast and cost-effective scaffold preparation and biofunctionalization is suitable for improved and prolonged JPC proliferation. Further studies should prove the functionality of composite scaffolds in vivo. Full article

(This article belongs to the Special Issue Materials and Technology for Regenerative Medicine)

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