A novel biomaterial for joint repair generated by self-organization : creation of a self-organized bone and cartilage-like tissue without a cell resource.

骨骼和软骨的破坏或退化发生在肌肉骨骼疾病中，如骨关节炎(OA)和类风湿性关节炎(RA)。最近，组织工程学和其他旨在重建关节的新技术引起了人们的注意。在关节软骨组织工程方面，通过自体软骨细胞或间充质干细胞与胶原凝胶的体外培养形成的三维材料已被植入，以在少数情况下替代软骨的缺陷部分。然而，需要几代细胞培养才能获得足够数量的细胞来进行组织工程。此外，还出现了软骨细胞的去分化、干细胞的恶性转化和分化等问题，这些问题需要从细胞资源的角度来解决。本研究的目的是创造一种新型的生物材料，具有与天然透明关节软骨…相当的功能和结构更多的是通过利用软骨基质成分本身的物理化学性质，换句话说，使用自组织技术而不是使用软骨细胞来产生软骨基质，最终导致关节软骨组织的形成。我们验证了自组织过程的条件和准确性，并利用电子显微镜和电子束显微镜对生成的微观结构进行了分析，以研究自组织所涉及的技术，这将适用于软骨样组织的生成。我们证明了包括II型胶原、蛋白多糖和透明质酸在内的几种软骨成分的自组装可以构建出自组装的软骨样组织，其特征是具有与人类关节软骨相似的纳米复合结构和与天然软骨一样小的低摩擦系数。因此，我们证明了我们能够在不使用细胞资源的情况下，仅使用基质成分来创建这样的组织。较少

Destruction or degeneration of bone and cartilage occurs in musculoskeletal diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA). Recently, attention has been drawn to tissue engineering and other novel techniques aimed at reconstruction of the joint. Regarding articular cartilage tissue engineering, three-dimensional materials created in vitro by cultivation of autologous chondrocytes or mesenchymal stem cells with a collagen gel have been implanted to replace defective parts of the cartilage in limited cases. However, several passages of cell culture are required to obtain a sufficient number of cells for tissue engineering. Additionally, several other problems arise including dedifferentiation of chondrocytes, malignant transformation and differentiation of stem cells which need to be solved from a viewpoint of cellular resources.The purpose of our study is to create a novel biomaterial possessing functions and structures comparable to native hyaline articular cartilag … More e by utilizing the physicochemical properties of the cartilage matrix components themselves, in other words, employing a self-organization technique instead of using chondrocytes to produce cartilage matrices eventually leading to articular cartilage tissue formation. We verified the conditions and accuracy of the self-organization process and analyzed the resulting micro structure using electron and electron beam microscopy in order to study the technique involved in the self-organization which would be applicable to creation of cartilage-like tissue. We demonstrated that self-assembly of several cartilage components including type II collagen, proteoglycan and hyaluronic acid could construct self-assembled cartilage-like tissues characterized by nano composite structures comparable to human articular cartilage and by low friction coefficients as small as those of native cartilage. We thus demonstrated that we are able to create such tissues using matrix components alone without using cellular resources. Less