Two-dimensional Nanomaterials for Cartilage Regeneration

摘要 骨关节炎（OA）是关节炎的最常见形式之一，并且以进行性退化为特征 软骨组织OA没有治愈方法，并且对疾病改善和治疗的医疗需求在很大程度上未得到满足。 对症治疗支持软骨基质的形态发生素和生长因子的全身递送 合成，如胰岛素样生长因子-1（IGF-1）和/或转化生长因子- β（TGF-β3），通常 由于关节内空间内缺乏血管供应而导致不良的改善。因此，本地化 关节内施用靶向软骨再生的生长因子已经成为一种有前途的治疗方法。 OA治疗干预策略。该R 03提案的目标是开发纳米硅酸盐， 持续递送OA修饰治疗剂（IGF-1/ TGF-β3）以促进软骨细胞增殖， 成熟我们的中心假设是持续释放OA修饰治疗剂将促进 软骨ECM产生。本工作的具体目的是：（1）了解 （2）研究治疗性负载的纳米硅酸盐诱导软骨形成的功效， 软骨ECM的分化和产生。拟议的研究具有巨大的变革性 在治疗传递、软骨再生、干细胞研究和OA治疗领域的潜力。 具体来说，该项目将引入纳米硅酸盐作为“即插即用”类型的治疗剂输送 各种组织工程应用的平台。此外，该项目还将从根本上 我们对矿物质诱导的细胞行为的理解发生了转变，开辟了一条全新的途径， 再生医学完成后，我们相信，我们的成果将产生重大的，积极的影响， 骨关节炎患者受损软骨的再生， 仍然有限。 !

ABSTRACT Osteoarthritis (OA) is one of the most common forms of arthritis and characterized by progressive degradation of cartilage. There is no cure for OA and is a largely unmet medical need for disease-modifying and symptomatic treatment. Systemic delivery of morphogens and growth factors supporting cartilage matrix synthesis, such as insulin like growth factor-1 (IGF-1) and/or transforming growth factor- β (TGF-β3), often results in poor improvement due to the lack of vascularity within intra-articular spaces. Therefore, localized intra-articular administration of growth factors targeting cartilage regeneration has emerged as a promising strategy for therapeutic intervention in OA. The objective of this R03 proposal is to develop nanosilicates for sustained delivery of OA-modifying therapeutics (IGF-1/ TGF-β3) to promote chondrocyte proliferation and maturation. Our central hypothesis is that sustain release of OA-modifying therapeutics will promote cartilaginous ECM production. The specific aims of this work are: (1) Understand the biological response of nanosilicates with human cells, and (2) Investigate the efficacy of therapeutic loaded nanosilicates to induce chondrogenic differentiation and production of cartilaginous ECM. The proposed research has tremendous transformative potential in the areas of therapeutic delivery, cartilage regeneration, stem cell research and OA treatment. Specifically, this project will introduce nanosilicates as a “plug-and-play” type of therapeutics delivery platform for various tissue-engineering applications. In addition, the project will also result in a fundamental shift in our understanding of mineral-induced cellular behavior, opening up an entirely new avenue in regenerative medicine. Upon completion, we believe that our results will have a significant, positive impact on regeneration of injured cartilage in patients suffering from osteoarthritis, for whom current treatment options remain limited. !