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Isotropic and Anisotropic Scaffolds for Tissue Engineering: Collagen, Conventional, and Textile Fabrication Technologies and Properties

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Isotropic and Anisotropic Scaffolds for Tissue Engineering: Collagen, Conventional, and Textile Fabrication Technologies and Properties International Journal of Molecular Sciences Review Isotropic and Anisotropic Scaffolds for Tissue Engineering: Collagen, Conventional, and Textile Fabrication Technologies and Properties Robert Tonndorf * , Dilbar Aibibu and Chokri Cherif Institute of Textile Machinery and High Performance Material Technology, Technische Universität Dresden, 01069 Dresden, Germany; [email protected] (D.A.); [email protected] (C.C.) * Correspondence: [email protected] Abstract: In this review article, tissue engineering and regenerative medicine are briefly explained and the importance of scaffolds is highlighted. Furthermore, the requirements of scaffolds and how they can be fulfilled by using specific biomaterials and fabrication methods are presented. Detailed insight is given into the two biopolymers chitosan and collagen. The fabrication methods are divided into two categories: isotropic and anisotropic scaffold fabrication methods. Processable biomaterials and achievable pore sizes are assigned to each method. In addition, fiber spinning methods and textile fabrication methods used to produce anisotropic scaffolds are described in detail and the advantages of anisotropic scaffolds for tissue engineering and regenerative medicine are highlighted. Keywords: scaffold; biomaterials; biopolymers; collagen; chitosan; pores; fibers; anisotropic; tex- tile; spinning Citation: Tonndorf, R.; Aibibu, D.; Cherif, C. Isotropic and Anisotropic Scaffolds for Tissue Engineering: Collagen, Conventional, and Textile 1. Introduction Fabrication Technologies and The two terms “regenerative medicine” and “tissue engineering” are used synony- Properties. Int. J. Mol. Sci. 2021, 22, mously as well as differently in the current literature. It is difficult to distinguish between 9561. https://doi.org/ both terms, as their descriptions have a great deal of intersection. The ideas and concepts 10.3390/ijms22179561 of “regenerative medicine” and “tissue engineering” have been used since the beginning of the 20th century: Alexis Carrel was developing techniques to cultivate cells in vitro and Academic Editor: Rivka Ofir was proposing with Charles Lindbergh to grow organs as early as the 1930s [1]. These concepts were focused exclusively on cells until the 1970s. By discovering the importance Received: 2 August 2021 of the extracellular matrix in the 1970s, the concept of “tissue engineering” was established Accepted: 31 August 2021 in the following decades. The term “regenerative medicine” has gained in importance Published: 3 September 2021 with the developments in stem cell research since the 2000s [2]. If a differentiated view of the two terms is indispensable, “tissue engineering” may be assigned to the engineering Publisher’s Note: MDPI stays neutral context and “regenerative medicine” to the medical or biological context. Likewise, both with regard to jurisdictional claims in terms can be summarized as “tissue engineering and regenerative medicine” (TERM). published maps and institutional affil- iations. 2. Tissue Engineering and Regenerative Medicine (TERM) 2.1. Fundamentals of Tissue Engineering and Regenerative Medicine The TERM approach is based on the interaction of up to three components (triad). New tissue forms by cultivating cells on cell carriers or scaffolds under the influence of Copyright: © 2021 by the authors. chemical or physical signals (Figure1). Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). Int. J. Mol. Sci. 2021, 22, 9561. https://doi.org/10.3390/ijms22179561 https://www.mdpi.com/journal/ijms Int. J. Mol. Sci. 2021 22 Int. J. Mol. Sci. 2021,, 22,, x 9561 FOR PEER REVIEW 2 of 2526 Figure 1. TheThe triad triad of of tissue tissue engineering engineering and regenerative medicine in the context of the in situ, in vivo and in vitro vitro sstrategytrategy with in vivo and ex vivo cell culture. with in vivo and ex vivo cell culture. TheThe cells used inin thethe TERMTERM areare mostly mostly stem stem cells. cells. These These cells cells can can self-renew self-renew in in terms terms of ofproliferation proliferation and and generate generate somatic somatic cells, cells, which which can proliferatecan proliferate only toonly a very to a limited very limited extent. extent.The relevant The relevant stem cells stem for cells TERM for areTERM mesenchymal are mesenchymal stem cells stem (MSCs) cells [(MSCs)3], embryonic [3], embry- stem oniccells stem (ESCs) cells [4], (ESCs) and induced [4], and pluripotent induced pluripotent stem cells stem (iPSCs) cells [5 ,(iPSCs)6]. [5,6]. ChemicalChemical signals suchsuch asas growthgrowth factors factors influence influence the the proliferation proliferation and and differentiation differentia- tionof cells. of cells. However, However, as the as bioactivity the bioactivity of growth of growth factors factors has a has short a short half-life half in-life physiological in physio- logicalenvironments, environments, delivery delivery systems systems are developed are developed for on-demand for on- growthdemand factor growth delivery factor [7 de-–9]. liveryPhysical [7– signals9]. Physical are equally signals a are focus equally of research a focus as of moderate research mechanical as moderate stimulation mechanical ensures stim- ulationmaintenance ensures of maintenance the natural phenotype of the natural of tissues phenotype [10]. of Mechanical tissues [10] stimulation. Mechanical methods stimu- lationare therefore methods used are totherefore generate used a specific to generate tissue a phenotype specific tissue in TERM phenotype such as in cartilage TERM such [11], astendon cartilage [12], [11] or cardiac, tendon muscle [12], or tissue cardiac [13 muscle]. tissue [13]. ScaffoldsScaffolds serve serve as as cell cell carriers in in the the form of of artificial artificial extracellular extracellular matrices matrices (ECMs). (ECMs). They determine thethe geometricgeometric template template for for the the tissue tissue to beto generatedbe generated by stabilizingby stabilizing cells cells and, and,if necessary, if necessar signaly, signal molecules molecules in a definedin a defined manner manner in three-dimensional in three-dimensional space. space. Scaffolds Scaf- foldsmust must have anhave open-pore an open structure-pore structure to allow to migration allow migration of cells andof cells nutrients. and nutrients. Many scaffolds Many scaffoldsemploy pore employ sizes pore between sizes between 100 and 100 400 andµm, 400 with µm, pore with sizes pore varying sizes varying depending depending on the onspecific the spec cellific and cell tissue and tissue type type [14]. [14] Therefore,. Therefore, the the fabrication fabrication method method of of scaffoldsscaffolds must enableenable adjustability of of the pore size. In addition, scaffolds control the proliferation and differentiation potential of cells through their material material-specific-specific properties such as surface chemistry,chemistry, roughness, structuring, and stiffnessstiffness (mechanotransduction)(mechanotransduction) [[1515––1717]].. After successfulsuccessful proliferation,proliferation, differentiation,differentiation, tissue tissu formation,e formation, and and optional optional vascularization, vascularization, the thescaffold scaffold material material must must degrade degrade without without leaving leaving residues. residues. Scaffold Scaffold materials materials can be can of eitherbe of eithersynthetic synthetic or natural or natural origin, origin, but they but have they to have possess to possess certain characteristicscertain characteristics to be suitable to be suitablefor TERM. for TheseTERM. include These goodinclude biocompatibility, good biocompatibility, biodegradability, biodegradability, biomimetics biomimetics (a structure (a Int. J. Mol. Sci. 2021, 22, 9561 3 of 25 and mechanical behavior similar to that of natural ECM), and sufficiently high mechanical stability under physiological conditions. 2.2. In Vivo, Ex Vivo, In Vitro, and In Situ The successive steps of cell culture: seeding, proliferation, differentiation, and tissue formation can take place either inside or outside the body. In case of the in vitro strategy, cells are obtained from the patient (autologous transplantation) or a donor (allogeneic transplantation), which are then seeded on a scaffold. After proliferation and differentiation, new tissue is formed, which is implanted in the defect of the body [18]. For the in vivo strategy, cells are obtained analogous to the in vitro strategy. However, proliferation and differentiation are started after seeding and implantation. For this purpose, the scaffold seeded with cells is implanted either directly in the defect site or at another site in the body, with the body serving as a bioreactor in each case [19]. In the in situ strategy, on the other hand, an acellular scaffold (without cells) is implanted into the defect site. Subsequently, the new tissue is formed by regenerative processes of the body after cells from the adjacent tissue migrate into the scaffold, proliferate, and differentiate [20]. However, a clear classification of the different strategies is difficult, as no clear boundary is drawn in the literature, especially between the in vivo and in situ strategies. In ex vivo cell culture, cells are cultivated outside a living organism under controlled conditions. The ex vivo cell culture technology
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