Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.
J Control Release. 2011 Sep 25;154(3):258-66. doi: 10.1016/j.jconrel.2011.06.027. Epub 2011 Jul 2.
Photocrosslinkable biomaterials are promising for tissue engineering applications due to their capacity to be injected and form hydrogels in situ in a minimally invasive manner. Our group recently reported on the development of photocrosslinked alginate hydrogels with controlled biodegradation rates, mechanical properties, and cell adhesive properties. In this study, we present an affinity-based growth factor delivery system by incorporating heparin into photocrosslinkable alginate hydrogels (HP-ALG), which allows for controlled, prolonged release of therapeutic proteins. Heparin modification had minimal effect on the biodegradation profiles, swelling ratios, and elastic moduli of the hydrogels in media. The release profiles of growth factors from this affinity-based platform were sustained for 3weeks with no initial burst release, and the released growth factors retained their biological activity. Implantation of bone morphogenetic protein-2 (BMP-2)-loaded photocrosslinked alginate hydrogels induced moderate bone formation around the implant periphery. Importantly, BMP-2-loaded photocrosslinked HP-ALG hydrogels induced significantly more osteogenesis than BMP-2-loaded photocrosslinked unmodified alginate hydrogels, with 1.9-fold greater peripheral bone formation and 1.3-fold greater calcium content in the BMP-2-loaded photocrosslinked HP-ALG hydrogels compared to the BMP-2-loaded photocrosslinked unmodified alginate hydrogels after 8weeks implantation. This sustained and controllable growth factor delivery system, with independently controllable physical and cell adhesive properties, may provide a powerful modality for a variety of therapeutic applications.
光交联生物材料在组织工程应用中具有广阔的前景，因为它们能够以微创的方式注入并原位形成水凝胶。我们小组最近报道了一种具有可控降解率、力学性能和细胞黏附性能的光交联海藻酸钠水凝胶的开发。在这项研究中，我们通过将肝素掺入光交联海藻酸钠水凝胶（HP-ALG）中，提出了一种基于亲和力的生长因子递药系统，该系统允许对治疗性蛋白进行可控、长效释放。肝素修饰对水凝胶在介质中的生物降解曲线、溶胀比和弹性模量几乎没有影响。这种基于亲和力的平台的生长因子释放曲线可持续 3 周，没有初始突释，并且释放的生长因子保留了其生物活性。负载骨形态发生蛋白-2（BMP-2）的光交联海藻酸钠水凝胶的植入物诱导了植入物周围适度的骨形成。重要的是，负载 BMP-2 的光交联 HP-ALG 水凝胶诱导的成骨作用明显多于负载 BMP-2 的未修饰的光交联海藻酸钠水凝胶，在 8 周植入后，负载 BMP-2 的光交联 HP-ALG 水凝胶的周边骨形成增加了 1.9 倍，钙含量增加了 1.3 倍。这种具有独立可控物理和细胞黏附性能的持续可控生长因子递药系统，可能为各种治疗应用提供一种强大的模式。
