pH-Responsive biodegradable hydrogels based on NIPAM/AA and a PLLA/PEG macro-crosslinker demonstrated pH mediated differential release of doxorubicin and tetracycline.

Background. Acrylate/acrylamide copolymers have excellent optical properties and biocompatibility and are ideal biomaterials that have been widely used in tissue engineering. Multilineage-differentiating stress-enduring cells (Muse cells) are a specific subset of mesenchymal stem cells that have an excellent potential for the regenerative medicine. Objective. This study was designed to investigate the effects of acrylate/acrylamide copolymers on the adhesion, proliferation and pluripotent-like properties of Muse cells, which were derived from normal human dermal fibroblasts by long-term trypsin incubation. Methods. In an initial experiment, Muse cells were seeded on primary microarrays containing micro-spots of 275 different mixtures of acrylate/acrylamide. Each mixture was composed of two of 11 different monomers in various proportions, and was replicated in four micro-spots each. According to the adhesion and growth characteristics of Muse cells on those substrates, specific polymer candidates for Muse cells were selected and secondary microarrays were prepared. We then observed the effects of those specific polymer candidates on the adherence, proliferation and differentiation of Muse cells and suitable candidates for their optimal culture were identified. Results. According to the adhesion and growth patterns of Muse cells on the primary microarrays, ten suitable mixtures of acrylate/acrylamide copolymers were identified. Muse cells grew well on six of those combinations and around the four other combinations of those polymer mixtures. Muse cells cultured on three of those combinations proliferated and differentiated into long spindle-shaped cells that looked like fibroblasts, while Muse cells cultured on one combination formed clusters that were ring-shaped. Muse cells cultured on some of those combinations of acrylate/acrylamide proliferated and formed clusters that appeared to be very healthy, whereas Muse cells cultured on other combinations formed clusters that expanded outwards. Conclusions. These results identified a polymer combination that was optimum for the adhesion, proliferation and maintenance of Muse cells in an undifferentiated state.

Human adipose derived stem cells (hASCs) were seeded onto polymer microarrays that had been fabricated using a variety of acrylate monomers to discover novel substrates that induced differentiation towards chondrocytes and osteoblasts. Flow cytometric analysis showed that both CD105 and CD49d positive hASCs increased rapidly with passage number on the lead polymers, while quantitative PCR analysis showed that the substrate synthesized from methacryloxyethyltrimethyl ammonium chloride, N,N-diethylaminoethyl methacrylate and cyclohexyl methacrylate enhanced chondrogenesis and osteogenensis some 4 and 25 times respectively in terms of the expression of SOX9 and ALP in differentiated stem cells. These copolymers substrates thus have great potential for application in the purification, generation and expansion of defined hASC's and the controlled differentiation of of cells for possible clinical application.

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