Reddi A H
Center for Tissue Regeneration and Repair, University of California-Davis, Medical Center, Sacramento 95817, USA.
Nat Biotechnol. 1998 Mar;16(3):247-52. doi: 10.1038/nbt0398-247.
Morphogenesis is the developmental cascade of pattern formation and body plan establishment, culminating in the adult form. It has formed the basis for the emerging discipline of tissue engineering, which uses principles of molecular developmental biology and morphogenesis gleaned through studies on inductive signals, responding stem cells, and the extracellular matrix to design and construct spare parts that restore function to the human body. Among the many organs in the body, bone has considerable powers for regeneration and is a prototype model for tissue engineering. Implantation of demineralized bone matrix into subcutaneous sites results in local bone induction. This model mimics sequential limb morphogenesis and has permitted the isolation of bone morphogens, such as bone morphogenetic proteins (BMPs), from demineralized adult bone matrix. BMPs initiate, promote, and maintain chondrogenesis and osteogenesis, but are also involved in the morphogenesis of organs other than bone. The symbiosis of the mechanisms underlying bone induction and differentiation is critical for tissue engineering and is governed by both biomechanics (physical forces) and context (microenvironment/extracellular matrix), which can be duplicated by biomimetic biomaterials such as collagens, hydroxyapatite, proteoglycans, and cell adhesion glycoproteins, including fibronectins and laminin. Rules of tissue architecture elucidated in bone morphogenesis may provide insights into tissue engineering and be universally applicable for all organs/tissues, including bones and joints.
形态发生是模式形成和身体结构建立的发育级联过程，最终形成成年形态。它构成了新兴的组织工程学科的基础，该学科利用通过对诱导信号、反应性干细胞和细胞外基质的研究收集到的分子发育生物学和形态发生原理，来设计和构建能够恢复人体功能的备用部件。在人体的众多器官中，骨骼具有相当强的再生能力，是组织工程的原型模型。将脱矿骨基质植入皮下部位会导致局部骨诱导。这个模型模拟了肢体的连续形态发生，并使得从脱矿的成年骨基质中分离出骨形态发生蛋白（BMPs）等骨形态发生因子成为可能。BMPs启动、促进并维持软骨形成和骨形成，但也参与骨骼以外其他器官的形态发生。骨诱导和分化背后机制的共生对于组织工程至关重要，并且受生物力学（物理力）和环境（微环境/细胞外基质）的共同支配，而胶原蛋白、羟基磷灰石、蛋白聚糖以及包括纤连蛋白和层粘连蛋白在内的细胞粘附糖蛋白等仿生生物材料可以复制这些因素。在骨形态发生中阐明的组织结构规则可能为组织工程提供见解，并普遍适用于所有器官/组织，包括骨骼和关节。
