There is an urgent, clinical need for an alternative to the use of autologous grafts for the ever increasing number of bone grafting procedures performed annually. Herein, we describe a developmentally inspired approach to bone tissue engineering, which focuses on leveraging biomaterials as platforms for recapitulating the process of endochondral ossification. To begin, we describe the traditional biomaterial-based approaches to tissue engineering that have been investigated as methods to promote in vivo bone regeneration, including the use of three-dimensional biomimetic scaffolds, the delivery of growth factors and recombinant proteins, and the in vitro engineering of mineralized bone-like tissue. Thereafter, we suggest that some of the hurdles encountered by these traditional tissue engineering approaches may be circumvented by modulating the endochondral route to bone repair and, to that end, we assess various biomaterials that can be used in combination with cells and signaling factors to engineer hypertrophic cartilaginous grafts capable of promoting endochondral bone formation. Finally, we examine the emerging trends in biomaterial-based approaches to endochondral bone regeneration, such as the engineering of anatomically shaped templates for bone and osteochondral tissue engineering, the fabrication of mechanically reinforced constructs using emerging three-dimensional bioprinting techniques, and the generation of gene-activated scaffolds, which may accelerate the field towards its ultimate goal of clinically successful bone organ regeneration.

对于每年越来越多的骨移植程序，迫切需要替代自体移植物的临床应用。在这里，我们描述了一种在骨组织工程学上受到发展启发的方法，该方法侧重于利用生物材料作为概述软骨内骨化过程的平台。首先，我们将描述基于传统生物材料的组织工程方法，这些方法已作为促进体内骨骼再生的方法进行了研究，包括使用三维仿生支架，生长因子和重组蛋白的递送以及体外矿化的骨样组织工程。之后，我们建议，可以通过调节软骨内骨修复途径来克服这些传统组织工程方法所遇到的一些障碍，为此，我们评估了可以与细胞和信号因子结合使用以工程化肥大软骨的各种生物材料能够促进软骨内骨形成的移植物。最后，我们研究了基于生物材料的软骨内骨再生方法的新兴趋势，例如用于骨骼和骨软骨组织工程的解剖形状模板的工程设计，使用新兴的三维生物打印技术制造机械增强的构造物以及基因激活的支架，可以加速该领域的发展，使其达到临床上成功进行骨器官再生的最终目标。