Department of Bioengineering and the McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Department of Bioengineering and the McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15260, USA; Department of Chemical and Petroleum Engineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Mechanical Engineering and Materials Science, University of Pittsburgh, Pittsburgh, PA 15261, USA; Clinical Translational Science Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Biomaterials. 2016 Dec;111:80-89. doi: 10.1016/j.biomaterials.2016.09.026. Epub 2016 Sep 30.
We designed and tested a versatile hydrogel for tissue regeneration by preserving the bioactivity of growth factors. The shear-thinning gel self-assembles within 1 min from heparin and Laponite-a silicate nanoparticle, thus the name HELP gel. By not covalently modifying heparin, it should retain its natural affinity towards many proteins anchored in the extracellular matrix. In principle, HELP gel can bind any heparin-binding growth factor; we use fibroblast growth factor-2 (FGF2) in this study to demonstrate its utility. Heparin in the gel protects FGF2 from proteolytic degradation and allows it to be released over time with preserved bioactivity. FGF2 released from subcutaneously injected gel induces strong angiogenesis in a mouse model. The hydrogel degrades completely in vivo in 8 weeks with or without growth factors, eliciting mild inflammatory response but having little impacts on the surrounding tissue. The ease of preparation and scale-up makes this protein delivery platform attractive for clinical translation.
我们设计并测试了一种通过保留生长因子的生物活性来促进组织再生的多功能水凝胶。该剪切稀化凝胶可在 1 分钟内由肝素和 Laponite（一种硅酸盐纳米颗粒）自组装而成，因此命名为 HELP 凝胶。由于没有对肝素进行共价修饰，它应该保留其对细胞外基质中锚定的许多蛋白质的天然亲和力。原则上，HELP 凝胶可以结合任何肝素结合生长因子；在本研究中，我们使用成纤维细胞生长因子 2（FGF2）来证明其用途。凝胶中的肝素可防止 FGF2 被蛋白水解降解，并使其随着时间的推移以保留生物活性的方式释放。从小鼠模型的皮下注射凝胶中释放的 FGF2 可诱导强烈的血管生成。水凝胶在 8 周内无论是否有生长因子都能完全在体内降解，引起轻微的炎症反应，但对周围组织的影响很小。该蛋白质递送平台易于制备和放大，因此具有临床转化的吸引力。
