Engineering of an Osteoinductive and Growth Factor-Free Injectable Bone-Like Microgel for Bone Regeneration.
Engineering of an Osteoinductive and Growth Factor-Free Injectable Bone-Like Microgel for Bone Regeneration.
复制标题
用于骨再生的骨诱导和无生长因子可注射骨样微凝胶的工程。
DOI：
10.1002/adhm.202200976
复制
发表时间：
2023
影响因子：
10
通讯作者：
Bertassoni,LuizE
中科院分区：
文献类型：
--
作者：
Subbiah,Ramesh;Lin,EdithY;Athirasala,Avathamsa;Romanowicz,GenevieveE;Lin,AngelaSP;Califano,JosephV;Guldberg,RobertE;Bertassoni,LuizE
自体骨移植仍然是骨移植手术的黄金标准，尽管供骨部位发病率增加，可获得性有限。骨形态发生蛋白负载的移植物是另一种成功的商业选择。然而，重组生长因子的治疗应用与显著的不良临床结果相关。这突显了开发接近自体骨移植结构和组成的生物材料的必要性，这种自体骨移植本质上具有骨诱导作用，并具有嵌入活细胞的生物学活性，而不需要添加补充剂。在这里，可注射的不含生长因子的骨样组织结构被开发出来，这种结构与自体骨移植的细胞、结构和化学成分非常接近。研究表明，这些微结构本身就是成骨的，并在体内临界大小的缺损处表现出刺激矿化组织形成和再生骨的能力。此外，尽管缺乏骨诱导补充剂，但仍评估了允许人骨髓间充质干细胞(HMSCs)在这些结构中高度成骨的机制，其中激活蛋白(YAP)核定位和腺苷信号似乎调节成骨细胞的分化。这一发现代表着朝着一种新型的微创、可注射和固有的骨诱导支架迈出了一步，这种支架凭借其模拟组织细胞和细胞外微环境的能力而具有再生性，从而显示出在再生工程中的临床应用前景。
Bone autografts remain the gold standard for bone grafting surgeries despite having increased donor site morbidity and limited availability. Bone morphogenetic protein‐loaded grafts represent another successful commercial alternative. However, the therapeutic use of recombinant growth factors has been associated with significant adverse clinical outcomes. This highlights the need to develop biomaterials that closely approximate the structure and composition of bone autografts, which are inherently osteoinductive and biologically active with embedded living cells, without the need for added supplements. Here, injectable growth factor‐free bone‐like tissue constructs are developed, that closely approximate the cellular, structural, and chemical composition of bone autografts. It is demonstrated that these micro‐constructs are inherently osteogenic, and demonstrate the ability to stimulate mineralized tissue formation and regenerate bone in critical‐sized defects in‐vivo. Furthermore, the mechanisms that allow human mesenchymal stem cells (hMSCs) to be highly osteogenic in these constructs, despite the lack of osteoinductive supplements, are assessed, whereby Yes activated protein (YAP) nuclear localization and adenosine signaling appear to regulate osteogenic cell differentiation. The findings represent a step toward a new class of minimally invasive, injectable, and inherently osteoinductive scaffolds, which are regenerative by virtue of their ability to mimic the tissue cellular and extracellular microenvironment, thus showing promise for clinical applications in regenerative engineering.