Bone fractures are the most common traumatic injuries in humans. The repair of bone fractures is a regenerative process that recapitulates many of the biological events of embryonic skeletal development. Most of the time it leads to successful healing and the recovery of the damaged bone. Unfortunately, about 5-10% of fractures will lead to delayed healing or non-union, more so in the case of co-morbidities such as diabetes. In this article, we review the different strategies to heal bone defects using synthetic bone graft substitutes and biologically active substances or stem cells. Our review is different from previous reviews, which focus on strategies that are still at the early stages of development and use mostly in vitro experiments with cell lines or stem cells. Here, we focus on what is already implemented in the clinics, what is currently in clinical trials, and what has been tested in animal models. Treatment approaches can be classified in three major categories: i) synthetic bone graft substitutes (BGS) whose architecture and surface can be optimized; ii) BGS combined with bioactive molecules such as growth factors, peptides or small molecules targeting bone precursor cells, bone formation and metabolism; iii) cell-based strategies with progenitor cells combined or not with active molecules that can be injected or seeded on BGS for improved delivery. We review the major types of adult stromal cells (bone marrow, adipose and periosteum derived) that have been used and compare their properties. Finally, we discuss the remaining challenges that need to be addressed to significantly improve the healing of bone defects.

骨折是人类最常见的外伤。骨折的修复是一个再生过程，概括了胚胎骨骼发育的许多生物事件。大多数时候，它会导致受损骨骼的成功愈合和恢复。不幸的是，大约 5-10% 的骨折会导致愈合延迟或不愈合，在糖尿病等并发症的情况下更是如此。在本文中，我们回顾了使用合成骨移植替代品和生物活性物质或干细胞来治愈骨缺损的不同策略。我们的评论与以前的评论不同，以前的评论侧重于仍处于开发早期阶段的策略，并且主要使用细胞系或干细胞的体外实验。在这里，我们重点关注临床中已经实施的内容、目前正在进行临床试验的内容以及已经在动物模型中进行测试的内容。治疗方法可分为三大类：i）合成骨移植替代品（BGS），其结构和表面可以优化； ii) BGS与针对骨前体细胞、骨形成和代谢的生物活性分子如生长因子、肽或小分子相结合； iii) 基于细胞的策略，祖细胞与活性分子结合或不结合，可以注射或接种在 BGS 上以改善递送。我们回顾了已使用的成体基质细胞（骨髓、脂肪和骨膜来源）的主要类型，并比较了它们的特性。最后，我们讨论了显着改善骨缺损愈合需要解决的剩余挑战。