The meniscus plays a critical role in maintaining the homeostasis, biomechanics, and structural stability of the knee joint. Unfortunately, it is predisposed to damages either from sports-related trauma or age-related degeneration. The meniscus has an inherently limited capacity for tissue regeneration. Self-healing of injured adult menisci only occurs in the peripheral vascularized portion, while the spontaneous repair of the inner avascular region seems never happens. Repair, replacement, and regeneration of menisci through tissue engineering strategies are promising to address this problem. Recently, many scaffolds for meniscus tissue engineering have been proposed for both experimental and preclinical investigations. Electrospinning is a feasible and versatile technique to produce nano-to micro-scale fibers that mimic the microarchitecture of native extracellular matrix and is an effective approach to prepare nanofibrous scaffolds for constructing engineered meniscus. Electrospun scaffolds are reported to be capable of inducing colonization of meniscus cells by modulating local extracellular density and stimulating endogenous regeneration by driving reprogramming of meniscus wound microenvironment. Electrospun nanofibrous scaffolds with tunable mechanical properties, controllable anisotropy, and various porosities have shown promises for meniscus repair and regeneration and will undoubtedly inspire more efforts in exploring effective therapeutic approaches towards clinical applications. In this article, we review the current advances in the use of electrospun nanofibrous scaffolds for meniscus tissue engineering and repair and discuss prospects for future studies.
Decellularized meniscus extracellular matrix (dmECM)‐based biological scaffolds in the forms of sponge, hydrogel, nanofiber, and composite have gained increasing interest in meniscus tissue engineering and regeneration. A common shortcoming of those scaffolds is insufficient mechanical strength and poor elasticity. Herein, we report a practicable protocol for milder meniscus decellularization to prepare elastic, porous dmECM scaffolds. Porcine meniscus was pulverized by cyclic freeze–thaw grinding and then treated with DNase to obtain fine dmECM particles. Individual dmECM particles were condensed to bulk preparation by centrifuge, followed by lyophilization to form blocks, and finally crosslinked by dehydrothermal treatment to obtain porous dmECM scaffolds. Our results show that the freeze–thaw grinding method was effective in removing cellular DNA with good retention of meniscus‐derived bioactive components. The dmECM scaffold had porous structure with interconnected mesopores and good mechanical properties. Primary articular chondrocytes proliferated robustly and maintained chondrogenic characteristics and produce abundant collagen on dmECM scaffolds. Evaluation of biocompatibility in a rat model shows that the dmECM scaffold elicited minor foreign body reactions, indicating effective antigen removal from dmECM. This study provides an alternative for preparing dmECM and fabricating porous scaffolds for meniscus repair and regeneration.
Previously, we demonstrated that magnesium oxide (MgO)‐incorporated electrospun membranes show powerful antibacterial activity and promote wound healing, but the underlying mechanisms have not been entirely understood. Herein, we investigated the relationship between structure and function of MgO‐incorporated membranes and interrogated critical bioactive cues that contribute to accelerated wound healing and functional restoration. Our results show that MgO‐incorporated membranes exhibit good flexibility and improved water vapor transmission rates (WVTRs) and sustained Mg2+ release in a simulated model of wounds. MgO‐incorporated membranes modulate macrophage phenotype to downregulate inflammatory response, contributing to alleviated inflammation and creating a favorable microenvironment for wound healing. Specifically, MgO‐incorporated membranes stimulate macrophages to shift to a pro‐healing M2 phenotype and upregulate pro‐healing cytokine of transforming growth factor‐beta 1 (TGF‐β1) and downregulate pro‐inflammatory cytokines under lipopolysaccharide (LPS) challenge conditions. Together with increased TGF‐β1 by macrophages, MgO‐incorporated membranes significantly boost the proliferation of fibroblasts and upregulate collagen production, thus driving granulation tissue formation and wound closure. MgO‐incorporated membranes promote angiogenesis by promoting tube formation and upregulating vascular endothelial growth factor (VEGF) production of endothelial cells. Rapid epithelialization of regenerated skin tissue is attributed to the balanced phenotype of keratinocytes between proliferative and terminally differentiated populations. In addition to coordinating keratinocyte phenotype, MgO‐incorporated membranes reduce the expression of inflammatory cytokine interleukin 1‐alpha (IL‐1α) therefore promoting hair follicle regeneration. These data provide mechanisms of MgO‐incorporated membranes that inhibit bacterial infection, alleviate inflammation, facilitate extracellular matrix production and epithelialization, and potentiate hair follicle regeneration.
Injury to the meniscus is a common occurrence in the knee joint and its management remains a significant challenge in the clinic. Appropriate cell source is essential to cell-based tissue regeneration and cell therapy. Herein, three commonly used cell sources, namely, bone marrow mesenchymal stem cell (BMSC), adipose-derived stem cell (ADSC), and articular chondrocyte, were comparatively evaluated to determine their potential for engineered meniscus tissue in the absence of growth factor stimulus. Cells were seeded on electrospun nanofiber yarn scaffolds that share similar aligned fibrous configurations with native meniscus tissue for constructing meniscus tissue in vitro. Our results show that cells proliferated robustly along nanofiber yarns to form organized cell-scaffold constructs, which recapitulate the typical circumferential fiber bundles of native meniscus. Chondrocytes exhibited different proliferative characteristics and formed engineered tissues with distinct biochemical and biomechanical properties compared to BMSC and ADSC. Chondrocytes maintained good chondrogenesis gene expression profiles and produced significantly increased chondrogenic matrix and form mature cartilage-like tissue as revealed by typical cartilage lacunae. In contrast, stem cells underwent predominately fibroblastic differentiation and generated greater collagen, which contributes to improved tensile strengths of cell-scaffold constructs in comparison to the chondrocyte. ADSC showed greater proliferative activity and increased collagen production than BMSC. These findings indicate that chondrocytes are superior to stem cells for constructing chondrogenic tissues while the latter is feasible to form fibroblastic tissue. Combination of chondrocytes and stem cells might be a possible solution to construct fibrocartilage tissue and meniscus repair and regeneration.
Graphene oxide (GO) was heavily used in the adsorption process of various heavy metal ions (such as copper (Cu) and iron (Fe) ions), resulting in a huge waste quantity of graphene oxide@metal ions complex. In this research, the authors try to solve this issue. Herein, the GO surface was loaded with divalent (Cu2+) and trivalent (Fe3+) heavy metal ions as a simulated waste of the heavy metal in various removal processes to form GO@Cu and (GO@Fe) composites, respectively. After that, the previous nanocomposites were used to remove cationic methylene blue (MB) dye. The prepared composites were characterized with a scanning electron microscope (SEM), transition electron microscope (TEM), Fourier transmission infrared (FTIR), Raman, and energy-dispersive X-ray (EDS) before and after the adsorption process. Various adsorption factors of the two composites towards MB-dye were investigated. Based on the adsorption isotherm information, the adsorption process of MB-dye is highly fitted with the Langmuir model with maximum capacities (mg g−1) (384.62, GO@Cu) and (217.39, GO@Fe). According to the thermodynamic analysis, the adsorption reaction of MB-species over the GO@Cu is exothermic and, in the case of GO@Fe, is endothermic. Moreover, the two composites presented excellent selectivity of adsorption of the MB-dye from the MB/MO mixture
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