Acta Biomaterialia ( IF 9.7 ) Pub Date : 2018-07-19 , DOI: 10.1016/j.actbio.2018.07.039 Heemin Kang , Yuze Zeng , Shyni Varghese
Osteochondral tissue repair remains a significant challenge in orthopedic surgery. Tissue engineering of osteochondral tissue has transpired as a potential therapeutic solution as it can effectively regenerate bone, cartilage, and the bone-cartilage interface. While advancements in scaffold fabrication and stem cell engineering have made significant progress towards the engineering of composite tissues, such as osteochondral tissue, new approaches are required to improve the outcome of such strategies. Herein, we discuss the use of a single-unit trilayer scaffold with depth-varying pore architecture and mineral environment to engineer osteochondral tissues in vivo. The trilayer scaffold includes a biomineralized bottom layer mimicking the calcium phosphate (CaP)-rich bone microenvironment, a cryogel middle layer with anisotropic pore architecture, and a hydrogel top layer. The mineralized bottom layer was designed to support bone formation, while the macroporous middle layer and hydrogel top layer were designed to support cartilage tissue formation. The bottom layer was kept acellular and the top two layers were loaded with cells prior to implantation. When implanted in vivo, these trilayer scaffolds resulted in the formation of osteochondral tissue with a lubricin-rich cartilage surface. The osteochondral tissue formation was a result of continuous differentiation of the transplanted cells to form cartilage tissue and recruitment of endogenous cells through the mineralized bottom layer to form bone tissue. Our results suggest that integrating exogenous cell-based cartilage tissue engineering along with scaffold-driven in situ bone tissue engineering could be a powerful approach to engineer analogs of osteochondral tissue. In addition to offering new therapeutic opportunities, such approaches and systems could also advance our fundamental understanding of osteochondral tissue regeneration and repair.
Statement of Significance
In this work, we describe the use of a single-unit trilayer scaffold with depth-varying pore architecture and mineral environment to engineer osteochondral tissues in vivo. The trilayer scaffold was designed to support continued differentiation of the donor cells to form cartilage tissue while supporting bone formation through recruitment of endogenous cells. When implanted in vivo, these trilayer scaffolds partially loaded with cells resulted in the formation of osteochondral tissue with a lubricin-rich cartilage surface. Approaches such as the one presented here that integrates ex vivo tissue engineering along with endochondral cell-mediated tissue engineering can have a significant impact in tissue engineering composite tissues with diverse cell populations and functionality.
中文翻译:
功能梯度多层支架,用于体内骨软骨组织工程
骨软骨组织修复仍然是整形外科手术中的重大挑战。骨软骨组织的组织工程学已经成为一种潜在的治疗解决方案,因为它可以有效地再生骨骼,软骨和骨-软骨界面。尽管支架制造和干细胞工程学的进步已在工程化复合组织(如软骨组织)方面取得了重大进展,但仍需要新的方法来改善此类策略的结果。在这里,我们讨论具有深度变化的孔结构和矿物质环境的单单元三层支架在体内工程化软骨组织的用途。该三层支架包括模仿富含磷酸钙(CaP)的骨微环境的生物矿化底层,具有各向异性孔结构的冷冻凝胶中间层和水凝胶顶层。矿化的底层被设计成支持骨形成,而大孔中间层和水凝胶顶层被设计成支持软骨组织形成。底层保持无细胞状态,顶层两层在植入前先装入细胞。体内植入时,这些三层支架导致具有富含润滑蛋白的软骨表面的骨软骨组织的形成。骨软骨组织的形成是移植细胞连续分化形成软骨组织和内源性细胞通过矿化的底层募集形成骨组织的结果。我们的结果表明,将外源性基于细胞的软骨组织工程与支架驱动的原位骨组织工程相结合可能是设计骨软骨组织类似物的有效方法。除了提供新的治疗机会外,此类方法和系统还可以增进我们对骨软骨组织再生和修复的基本了解。
重要声明
在这项工作中,我们描述了使用具有深度变化的孔结构和矿物质环境的单单元三层支架在体内工程化骨软骨组织。三层支架被设计成支持供体细胞的持续分化以形成软骨组织,同时通过募集内源性细胞来支持骨形成。当植入体内时,这些三层支架部分装载了细胞,导致形成了具有富含润滑素的软骨表面的软骨组织。诸如此处介绍的一种离体整合方法 组织工程与软骨细胞介导的组织工程一起可以在具有多种细胞群和功能的复合组织的组织工程中产生重大影响。