Development and Utilization of Multifunctional Polymeric Scaffolds for the Regulation of Physical Cellular Microenvironments

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.

Enhanced Peripheral Nerve Regeneration by Mechano-electrical Stimulation

“…However, the poor mechanical properties with a typically rapid degradation rate, limit the use of natural materials as nerve guidance conduits in vivo 3,41 . To overcome this limitation, numerous biocompatible synthetic materials were developed as nerve guidance conduits with certain physical properties to achieve the desired peripheral nerve regeneration [42][43][44] . These synthetic conduits provide additional functionality to the structural support of the conduits to further enhance nerve regeneration.…”

Multifunctional Scaffolds Based on Emulsion and Coaxial Electrospinning Incorporation of Hydroxyapatite for Bone Tissue Regeneration

“…There, both the traditional techniques (e.g., polymer sponge, leaching, freeze-drying, or foaming) and the procedures that allow a high control over microstructure are discussed (e.g., 3D printing and electrospinning). The role of stimuli to activate the multifunctionalized scaffolds to direct cellular behaviours is discussed in detail by Tai et al [ 58 ]. The synthesis of architecturally controlled polymers seems a new great avenue for the development of scaffolds for tissue engineering.…”

Strategies for Enhancing Vascularization of Biomaterial‐Based Scaffold in Bone Regeneration

“…[149] Bone possesses piezoelectric properties that convert biophysical stimuli into bioelectrical signals causing necessary reformation/bone repair influenced by external and internal forces. [104,150,151] This encouraged development of piezoelectric scaffolds to perform mechano-transduction without external forces which activate a biological protein/molecular cascade controlling the GF upregulation. For example, a piezoelectric 3D-electrospun biodegradable polymeric/silicate/HA scaffold developed by Gorodzha et al effectively refined the adhesive and mineralization characteristics of MSC-origin osteoblasts.…”

“…Bone possesses piezoelectric properties that convert biophysical stimuli into bioelectrical signals causing necessary reformation/bone repair influenced by external and internal forces [104,150,151] . This encouraged development of piezoelectric scaffolds to perform mechano‐transduction without external forces which activate a biological protein/molecular cascade controlling the GF upregulation.…”