Abstract
Polymeric biomaterials exhibit excellent physicochemical characteristics as a scaffold for cell and tissue engineering applications. Chemical modification of the polymers has been the primary mode of functionalization to enhance biocompatibility and regulate cellular behaviors such as cell adhesion, proliferation, differentiation, and maturation. Due to the complexity of the in vivo cellular microenvironments, however, chemical functionalization alone is usually insufficient to develop functionally mature cells/tissues. Therefore, the multifunctional polymeric scaffolds that enable electrical, mechanical, and/or magnetic stimulation to the cells, have gained research interest in the past decade. Such multifunctional scaffolds are often combined with exogenous stimuli to further enhance the tissue and cell behaviors by dynamically controlling the microenvironments of the cells. Significantly improved cell proliferation and differentiation, as well as tissue functionalities, are frequently observed by applying extrinsic physical stimuli on functional polymeric scaffold systems. In this regard, the present paper discusses the current state-of-the-art functionalized polymeric scaffolds, with an emphasis on electrospun fibers, that modulate the physical cell niche to direct cellular behaviors and subsequent functional tissue development. We will also highlight the incorporation of the extrinsic stimuli to augment or activate the functionalized polymeric scaffold system to dynamically stimulate the cells.
Highlights
Both naturally derived and synthetic, have gained increased interest in the structural materials of tissue engineering scaffolds due to many advantages. These include the broad spectrum of biocompatible polymeric materials that can be used as tissue and cell culture platforms, the flexibility of the polymers that can be fabricated into various shapes with desired morphological features such as pores and their interconnectivity conducive to cell in-growth, and the existing mature synthesis technologies that enable the polymeric scaffolds to be and reproducibly produced
The gelatin-methacrylate hydrogel containing carbon nanotubes (CNT) was shown to promote myocardial cell attachment, organization, and cell-cell communication by Shin et al [64]., while SWNTs blended into collagen scaffolds promoted cardiomyocyte adhesion and proliferation, which was shown by Sun et al [48]
The results showed that distinct colony morphologies were observed depending on the scaffold stiffness, which in turn affected the differentiation tendency of stem cells; induced pluripotent stem cells (iPSCs) cultured on the stiffer substrate tended to differentiate more towards mesendodermal lineage while more ectodermal differentiation was observed on the softer substrate
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Typical tissue engineering strategies utilize scaffolds as a synthetic alternative for the natural extracellular matrix (ECM) to temporally support the cells, which require a 3D microenvironment resembling the in vivo conditions to develop a tissue with an appropriate structure and function. Due to the complexity of cellular microenvironments in the native tissues, chemical modification is usually insufficient to fully develop functionalized tissues in vitro In this regard, the control over physical microenvironments, including electrical, mechanical, and magnetic factors, has gained significant interest since they have been recently shown to crucially influence cellular behaviors, such as migration, proliferation, differentiation, and maturation, as well as to enhance tissue regeneration in bone, nerve, and blood vessels (Figure 1). We list and discuss the challenges and future directions regarding the use of multi-functional polymeric scaffolds in tissue engineering applications
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