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、活动能力丧失，最终需要用塑料和金属假体替换关节。虽然全关节置换术可以减轻疼痛，但一个主要的缺点是膝关节置换术患者必须停止跑步和跳跃。这就是为什么整形外科医生开发了刺激软骨修复的技术，但很多时候这些疗法都没有完全成功。我们的最终研究目标是开发可靠的一次性软骨修复疗法，作为简单的现成产品，可以在整个加拿大骨科医生的门诊诊所使用。我们最近发现用一种叫壳聚糖的聚合物稳定的血凝块植入物可以帮助软骨再生。为了更好地理解它是如何工作的，我们计划把从血块中提取出来的血清，和壳聚糖混合，看看血清是如何改变壳聚糖颗粒的大小的。我们注意到血清以某种方式帮助壳聚糖进入细胞，我们认为修复细胞识别壳聚糖和对壳聚糖作出反应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能帮助凝血酶分解补体蛋白，从而产生一种叫做补体C5a的有效蛋白片段。补体C5a可以通过招募巨噬细胞来帮助修复受损的软骨，巨噬细胞可以清除伤口的碎片和死细胞，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到受损的软骨。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一般理解。

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.