Meniscal Regenerative Scaffolds Based on Biopolymers and Polymers: Recent Status and Applications

Abstract

Knee menisci are structurally complex components that preserve appropriate biomechanics of the knee. Meniscal tissue is susceptible to injury and cannot heal spontaneously from most pathologies, especially considering the limited regenerative capacity of the inner avascular region. Conventional clinical treatments span from conservative therapy to meniscus implantation, all with limitations. There have been advances in meniscal tissue engineering and regenerative medicine in terms of potential combinations of polymeric biomaterials, endogenous cells and stimuli, resulting in innovative strategies. Recently, polymeric scaffolds have provided researchers with a powerful instrument to rationally support the requirements for meniscal tissue regeneration, ranging from an ideal architecture to biocompatibility and bioactivity. However, multiple challenges involving the anisotropic structure, sophisticated regenerative process, and challenging healing environment of the meniscus still create barriers to clinical application. Advances in scaffold manufacturing technology, temporal regulation of molecular signaling and investigation of host immunoresponses to scaffolds in tissue engineering provide alternative strategies, and studies have shed light on this field. Accordingly, this review aims to summarize the current polymers used to fabricate meniscal scaffolds and their applications in vivo and in vitro to evaluate their potential utility in meniscal tissue engineering. Recent progress on combinations of two or more types of polymers is described, with a focus on advanced strategies associated with technologies and immune compatibility and tunability. Finally, we discuss the current challenges and future prospects for regenerating injured meniscal tissues.

Enhanced Cellular Cryopreservation by Biopolymer-Associated Suppression of RhoA/ROCK Signaling Pathway

“…These findings provide another perspective for cell cryopreservation using cell-interactive cryoprotectants. In addition, since biopolymers have advantages of high biocompatibility and low cytotoxicity compared with petroleum-based synthetic polymers [ 27 , 29 ], cryopreservation medium supplemented with HA and low concentration of DMSO would be beneficial for clinical applications. Since CD44, a receptor for HA in fibroblasts, could regulate collagen accumulation and fibroblast motility [ 52 , 53 , 54 ], further studies are needed to investigate the effect of supplemented HAs on cellular functions such as ECM production.…”

“…Although synthetic, non-biodegradable polymer-based cryoprotectants were effective in reducing the size of ice crystals, their residues could potentially lead to less biocompatibility in vivo environments [ 26 ]. Recently, biodegradable polymeric cryoprotectants have gained special interest as cryoprotectants due to their complete enzymatic degradation in vivo and excellent biocompatibility [ 5 , 11 , 27 , 28 , 29 ]. Natural biopolymers can induce the release of various growth factors through cell interaction to maintain tissue regulation and homeostasis.…”

Biomaterials and Meniscal Lesions: Current Concepts and Future Perspective

“…Thus, hybrid scaffolds are suitable for meniscal tissue engineering. The general design strategy consists of synthetic polymers as a supporting framework, with natural polymers more likely serving as an additive microenvironment to mimic extracellular microenvironments, whereas cells and bioactive factors may further assist in improving cell recruitment, proliferation and differentiation, and may ultimately improve regeneration [98].…”

“…In general, bioprinting technologies mainly applied in meniscus or cartilage tissue engineering can be classified as follows: 3D plotting/direct ink writing, stereolithography (SLA), selective laser sintering (SLS), fused deposition modeling (FDM) and extrusionbased bioprinting [101]. Tissue menisci scaffolds produced by extrusion bioprinting techniques have high yields and excellent structural integrity, and this technique is most applied in meniscal regeneration [98]. Numerous polymers have been extensively studied to serve as bio-inks in 3D printing for tissue engineering.…”

“…In conclusion, the excellent ability of 3D bioprinting technology to precisely control the fiber diameter, orientation and microarchitecture endows the resulting constructs with promising mechanical properties and favorable biological functions. Therefore, it is one of the most attractive and promising technologies for tissue engineering applications, particularly meniscal regeneration [98].…”