Serum factors that mediate cell internalization of biomaterial scaffolds

在受损的软骨上行走会导致关节退化、疼痛、失去活动能力，最终需要使用塑料和金属假体进行关节置换。尽管全关节置换可以缓解疼痛，但一个主要的缺点是，膝关节置换的患者不得不停止跑步和跳跃。这就是为什么骨科医生开发了刺激软骨修复的技术，但许多时候这些疗法并不完全成功。我们的最终研究目标是开发可靠的一次性软骨修复疗法，作为一种简单的现成产品，可供整形外科医生在整个加拿大门诊诊所使用。我们最近发现，用一种名为壳聚糖的聚合物稳定的血液凝块植入物可以帮助再生软骨。为了更好地了解这一原理，我们计划提取从血栓中渗出的血清，并将其与壳聚糖混合，看看血清如何改变壳聚糖颗粒的大小。我们注意到血清以某种方式帮助壳聚糖进入细胞，我们相信修复细胞识别和反应壳聚糖的方式取决于某些血清蛋白与聚合物结合的紧密程度。我们还想看看壳聚糖是否有助于一种名为凝血酶的凝血因子切割补体蛋白，以产生一种名为补体C5a的有效蛋白质片段。补体C5a可以通过招募被称为巨噬细胞的细胞来帮助修复受损的软骨，巨噬细胞可以清理伤口的碎片和死亡细胞，并为新组织在健康的血液供应下生长铺平道路。最后，我们计划测试如何使用壳聚糖、血清因子和骨髓细胞的组合来引导伤口愈合的巨噬细胞修复受损的软骨。这种分子到组织的方法将提高我们对如何使用一次性治疗设备再生软骨的总体理解。

Walking around on damaged cartilage can lead to joint degeneration, pain, loss of mobility, and ultimately the need for joint replacement with a plastic and metal prosthesis. Although a total joint replacement can alleviate pain, one major downside is that patients with knee replacements have to stop running and jumping. This is why orthopedic surgeons have developed techniques to stimulate cartilage repair but many times these therapies fall short of complete success. Our ultimate research aim is to develop reliable, one-shot cartilage repair therapies, as simple off-the-shelf products that can be used throughout Canadian out-patient clinics by orthopedic surgeons. We recently discovered that blood clot implants stabilized with a polymer called chitosan can help regenerate cartilage. To better understand how this works, we plan to take serum that weeps out of blood clots, and mix it with chitosan, and see how serum changes the size of the chitosan particles. We noticed that serum somehow helps chitosan get inside of cells, and we believe that the way repair cells recognize and react to chitosan depends on how tightly certain serum proteins bind to the polymer. We also would like to see whether chitosan helps a clotting factor called thrombin to chop up complement protein to generate a potent protein fragment called complement C5a. Complement C5a could help repair damaged cartilage by recruiting cells called macrophages that cleanse the wound of debris and dead cells, and pave the way for new tissue to grow with a healthy blood supply. Finally, we plan to test how combinations of chitosan, serum factors, and bone marrow cells can be used to guide wound-healing macrophages to damaged cartilage. This molecules-to-tissues approach will improve our general understanding of how to regenerate cartilage using one-shot therapeutic devices.