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首页> 外文期刊>BioResearch open access. >Tissue Engineering Whole Bones Through Endochondral Ossification: Regenerating the Distal Phalanx
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Tissue Engineering Whole Bones Through Endochondral Ossification: Regenerating the Distal Phalanx

机译：通过软骨内骨化组织工程化整个骨骼：再生远端指骨

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Novel strategies are urgently required to facilitate regeneration of entire bones lost due to trauma or disease. In this study, we present a novel framework for the regeneration of whole bones by tissue engineering anatomically shaped hypertrophic cartilaginous grafts in vitro that subsequently drive endochondral bone formation in vivo. To realize this, we first fabricated molds from digitized images to generate mesenchymal stem cell-laden alginate hydrogels in the shape of different bones (the temporomandibular joint [TMJ] condyle and the distal phalanx). These constructs could be stimulated in vitro to generate anatomically shaped hypertrophic cartilaginous tissues that had begun to calcify around their periphery. Constructs were then formed into the shape of the distal phalanx to create the hypertrophic precursor of the osseous component of an engineered long bone. A layer of cartilage engineered through self-assembly of chondrocytes served as the articular surface of these constructs. Following chondrogenic priming and subcutaneous implantation, the hypertrophic phase of the engineered phalanx underwent endochondral ossification, leading to the generation of a vascularized bone integrated with a covering layer of stable articular cartilage. Furthermore, spatial bone deposition within the construct could be modulated by altering the architecture of the osseous component before implantation. These findings open up new horizons to whole limb regeneration by recapitulating key aspects of normal bone development.
机译：迫切需要新的策略来促进由于创伤或疾病而丢失的整个骨骼的再生。在这项研究中，我们提出了一种新的框架，该框架通过在体外组织工程解剖学形状的肥大性软骨移植物再生整个骨骼，随后在体内驱动软骨内骨骼的形成。为了实现这一点，我们首先从数字化图像中制造了模具，以生成具有不同骨骼（颞下颌关节[TMJ] con和远端指骨）形状的间充质干细胞的藻酸盐水凝胶。可以在体外刺激这些构建体以产生解剖形状的肥大性软骨组织，该组织开始在其周围钙化。然后将构造体形成为指骨的远端，以产生经工程改造的长骨的骨成分的肥大前体。通过软骨细胞自组装工程化的软骨层充当这些构建体的关节表面。在进行软骨致敏灌注和皮下植入后，工程指节的肥大期经历了软骨内骨化，从而导致形成了血管化骨，并整合了稳定的关节软骨覆盖层。此外，可以通过在植入之前改变骨成分的结构来调节构建体中的空间骨沉积。这些发现通过概括正常骨骼发育的关键方面，为全肢再生开辟了新视野。

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