Tissue engineering. Part A
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Microfracture of cartilage induces migration of bone-marrow-derived mesenchymal stem cells. However, this treatment often results in fibrocartilage regeneration. Growth factors such as bone morphogenetic protein (BMP)-2 induce the differentiation of bone-marrow-derived mesenchymal stem cells into chondrocytes, which can be used for hyaline cartilage regeneration. ⋯ A biochemical assay, real-time polymerase chain reaction assay and Western blot analysis all revealed that the long-term delivery of BMP-2 group had the highest glucosaminoglycan content as well as the highest expression level of collagen type II. Taken together, the long-term delivery of BMP-2 to cartilage defects subjected to microfracture resulted in regeneration of hyaline-like cartilage, as opposed to short-term delivery or no BMP-2 delivery. Therefore, this method could be more convenient for hyaline cartilage regeneration than autologous chondrocyte implantation due to its less invasive nature and lack of cell implantation.
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Normal human epidermis possesses a transepithelial potential (TEP) that varies in different parts of the body (10–60mV). The role of TEP in normal epidermis is not yet identified; but after skin injury, TEP disruption induces an endogenous direct current electric field (100–200mV/mm) directed toward the middle of the wound. This endogenous electric field could be implicated in the wound healing process by attracting cells, thus facilitating reepithelialization. ⋯ Taken together, these results suggest that the variations in the expression of Na+/K+ ATPase pump over time and across epidermis would be a determinant parameter of the TEP, dictating a cationic transport during the formation and restoration of the epidermis. Therefore, this study brings a new perspective to understand the formation and restoration of TEP during the cutaneous wound healing process. This might have important future medical applications regarding the treatment of chronic wound healing.
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The repair of bone defects can be induced experimentally with bone morphogenetic protein-2 (BMP-2) producing fat-derived stem cells, but this ex vivo tissue engineering method requires the isolation and long-term culture of autologous cells. To develop an expedited bone repair strategy, we transferred BMP-2 cDNA directly to autologous fat tissue fragments that were held in culture for only 24 h before implantation. We evaluated the ability of such gene-activated fat grafts to regenerate large segmental bone defects in rats. ⋯ The femora of this group exceeded the bone volume and the biomechanical stability of intact, contralateral femora. Control defects receiving no treatment, unmodified fat tissue, or GFP-transduced fat were filled with fibrous or adipose tissue, as evaluated by histology. The use of BMP-2 gene-activated fat tissue grafts represents an expedited and effective bone repair strategy that does not require the extraction and expansion of stem cells.
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Adult mesenchymal stem cells (MSCs) are considered promising candidate cells for therapeutic cartilage and bone regeneration. Because tissue regeneration and embryonic development may involve similar pathways, understanding common pathways may lead to advances in regenerative medicine. In embryonic limb development, fibroblast growth factor receptors (FGFRs) play a role in chondrogenic differentiation. ⋯ To evaluate whether stage-specific modulation of chondrogenic differentiation in MSCs is possible with different subtypes of FGF, FGF2 and FGF9 were added to the chondrogenic medium during different stages in the culture process (early or late). FGF2 and FGF9 differentially affected the amount of cartilage formed by MSCs depending on the stage in which they were added. These results will help us understand the role of FGF signaling in chondrogenesis and find new tools to monitor and control chondrogenic differentiation.
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Longitudinally oriented microstructures are essential for a nerve scaffold to promote significant regeneration of injured peripheral axons across nerve gaps. Extensive attention has been devoted to develop scaffolds with inner structures mimicking the nerve-guiding basal lamina microchannels in autografts. However, to date, little information has been obtained about scaffolds with similar inner microstructures, and the efficacy of such scaffolds in bridging peripheral nerve gaps in vivo has never been examined. ⋯ We evaluated the efficacy of the CCH scaffold to bridge a 15-mm-long sciatic nerve defect in rats using a combination of morphological and functional techniques. The in vivo animal study showed that the CCH scaffold achieved nerve regeneration and functional recovery equivalent to that of an autograft, without the exogenous delivery of regenerative agents or cell transplantation. These findings demonstrate that CCH scaffolds may be used as alternatives to nerve autografts for peripheral nerve regeneration.