Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.
Biomaterials. 2012 May;33(13):3503-14. doi: 10.1016/j.biomaterials.2012.01.041. Epub 2012 Feb 13.
Recently, we reported on a new photocrosslinkable alginate-based hydrogel, which has controllable physical and cell adhesive properties. The macromer solution containing cells can be injected in a minimally invasive manner into a defect site and crosslinked while maintaining high cell viability. The number of hydrolyzable ester bonds in the formed crosslinks may be controlled by altering the degree of methacrylation on the alginate polymer backbone. However, the degradation rate of the hydrogels has been found to be slower in vivo than in vitro. The purpose of this study was to develop photocrosslinked alginate hydrogels with an increased range of biodegradation rates for more rapid in vivo biodegradation in regenerative medicine and bioactive factor delivery applications. Therefore, we oxidized alginate prior to methacrylation to change the uronate residue conformations to an open-chain adduct, which makes it more vulnerable to hydrolysis. Here, we demonstrate that the swelling behavior, degradation profiles, and storage moduli of photocrosslinked hydrogels formed from oxidized, methacrylated alginates (OMAs) are tunable by varying the degree of alginate oxidation. The OMA macromers and photocrosslinked OMA hydrogels exhibited cytocompatibility when cultured with human bone marrow-derived mesenchymal stem cells (hBMMSCs). In addition, hMSCs derived from bone marrow or adipose tissue photoencapsulated within these hydrogels remained viable, and their proliferation rate was a function of alginate oxidation level and initial hydrogel weight fraction. Oxidation permits a wider range of photocrosslinked OMA hydrogels physical properties, which may enhance these therapeutic materials' utility in tissue engineering and other biomedical applications.
最近,我们报道了一种新的光交联海藻酸盐水凝胶,该水凝胶具有可控制的物理和细胞黏附特性。含有细胞的大分子溶液可以微创方式注入到缺陷部位,并在保持高细胞活力的同时交联。形成的交联中可水解酯键的数量可以通过改变海藻酸盐聚合物主链上的甲基丙烯酰化程度来控制。然而,水凝胶的体内降解速度比体外慢。本研究的目的是开发具有更高降解率范围的光交联海藻酸盐水凝胶,以实现再生医学和生物活性因子递送应用中更快速的体内生物降解。因此,我们在甲基丙烯酰化之前对海藻酸盐进行氧化,以将糖醛酸残基构象改变为开链加合物,使其更容易发生水解。在这里,我们证明了通过改变海藻酸盐氧化程度,可以调节光交联氧化、甲基丙烯酰化海藻酸盐(OMAs)形成的水凝胶的溶胀行为、降解曲线和存储模量。OMA 大分子和光交联 OMA 水凝胶在与骨髓间充质干细胞(hBMMSCs)共培养时表现出细胞相容性。此外,在这些水凝胶中光固化的骨髓或脂肪组织来源的 hMSCs 仍然存活,其增殖率是海藻酸盐氧化水平和初始水凝胶重量分数的函数。氧化允许更广泛的光交联 OMA 水凝胶物理性质,这可能增强这些治疗材料在组织工程和其他生物医学应用中的效用。