An artificial membrane binding protein-polymer surfactant nanocomplex facilitates stem cell adhesion to the cartilage extracellular matrix

Manuscript accepted in Biomaterial

Repair of Torn Avascular Meniscal Cartilage Using Undifferentiated Autologous Mesenchymal Stem Cells:From In Vitro Optimization to a First-in-Human Study

Meniscal cartilage tears are common and predispose to osteoarthritis (OA). Most occur in the avascular portion of the meniscus where current repair techniques usually fail. We described previously the use of undifferentiated autologous mesenchymal stem cells (MSCs) seeded onto a collagen scaffold (MSC/collagen-scaffold) to integrate meniscal tissues in vitro. Our objective was to translate this method into a cell therapy for patients with torn meniscus, with the long-term goal of delaying or preventing the onset of OA. After in vitro optimization, we tested an ovine-MSC/collagen-scaffold in a sheep meniscal cartilage tear model with promising results after 13 weeks, although repair was not sustained over 6 months. We then conducted a single center, prospective, open-label first-in-human safety study of patients with an avascular meniscal tear. Autologous MSCs were isolated from an iliac crest bone marrow biopsy, expanded and seeded into the collagen scaffold. The resulting human-MSC/collagen-scaffold implant was placed into the meniscal tear prior to repair with vertical mattress sutures and the patients were followed for 2 years. Five patients were treated and there was significant clinical improvement on repeated measures analysis. Three were asymptomatic at 24 months with no magnetic resonance imaging evidence of recurrent tear and clinical improvement in knee function scores. Two required subsequent meniscectomy due to retear or nonhealing of the meniscal tear at approximately 15 months after implantation. No other adverse events occurred. We conclude that undifferentiated MSCs could provide a safe way to augment avascular meniscal repair in some patients. Registration: EU Clinical Trials Register, 2010-024162-22. © Stem Cells Translational Medicine 2016

New three-dimensional poly(decanediol-co-tricarballylate) elastomeric fibrous mesh fabricated by photoreactive electrospinning for cardiac tissue engineering applications

Reactive electrospinning is capable of efficiently producing in situ crosslinked scaffolds resembling the natural extracellular matrix with tunable characteristics. In this study, we aimed to synthesize, characterize, and investigate the in vitro cytocompatibility of electrospun fibers of acrylated poly(1,10-decanediol-co-tricarballylate) copolymer prepared utilizing the photoreactive electrospinning process with ultraviolet radiation for crosslinking, to be used for cardiac tissue engineering applications. Chemical, thermal, and morphological characterization confirmed the successful synthesis of the polymer used for production of the electrospun fibrous scaffolds with more than 70% porosity. Mechanical testing confirmed the elastomeric nature of the fibers required to withstand cardiac contraction and relaxation. The cell viability assay showed no significant cytotoxicity of the fibers on cultured cardiomyoblasts and the cell-scaffolds interaction study showed a significant increase in cell attachment and growth on the electrospun fibers compared to the reference. This data suggests that the newly synthesized fibrous scaffold constitutes a promising candidate for cardiac tissue engineering applications

Chondrogenic differentiation of human chondrocytes cultured in the absence of ascorbic acid

Bioreactor systems will likely play a key role in establishing regulatory compliant and cost‐effective production systems for manufacturing engineered tissue grafts for clinical applications. However, the automation of bioreactor systems could become considerably more complex and costly due to the requirements for additional storage and liquid handling technologies if unstable supplements are added to the culture medium. Ascorbic acid (AA) is a bioactive supplement that is commonly presumed to be essential for the generation of engineered cartilage tissues. However, AA can be rapidly oxidized and degraded. In this work, we addressed whether human nasal chondrocytes can redifferentiate, undergo chondrogenesis, and generate a cartilaginous extracellular matrix when cultured in the absence of AA. We found that when chondrocytes were cultured in 3D micromass pellets either with or without AA, there were no significant differences in their chondrogenic capacity in terms of gene expression or the amount of glycosaminoglycans. Moreover, 3D pellets cultured without AA contained abundant collagen Types II and I extracellular matrix. Although the amounts of Collagens II and I were significantly lower (34% and 50% lower) than in pellets cultured with AA, collagen fibers had similar thicknesses and distributions for both groups, as shown by scanning electron microscopy imaging. Despite the reduced amounts of collagen, if engineered cartilage grafts can be generated with sufficient properties that meet defined quality criteria without the use of unstable supplements such as AA, bioreactor automation requirements can be greatly simplified, thereby facilitating the development of more compact, user‐friendly, and cost‐effective bioreactor‐based manufacturing systems