Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC 27710, United States.
Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, United States.
Acta Biomater. 2018 Sep 15;78:329-340. doi: 10.1016/j.actbio.2018.06.035. Epub 2018 Jun 30.
Emerging studies show the potential application of synthetic biomaterials that are intrinsically osteoconductive and osteoinductive as bone grafts to treat critical bone defects. Here, the biomaterial not only assists recruitment of endogenous cells, but also supports cellular activities relevant to bone tissue formation and function. While such biomaterial-mediated in situ tissue engineering is highly attractive, success of such an approach relies largely on the regenerative potential of the recruited cells, which is anticipated to vary with age. In this study, we investigated the effect of the age of the host on mineralized biomaterial-mediated bone tissue repair using critical-sized cranial defects as a model system. Mice of varying ages, 1-month-old (juvenile), 2-month-old (young-adult), 6-month-old (middle-aged), and 14-month-old (elderly), were used as recipients. Our results show that the bio-mineralized scaffolds support bone tissue formation by recruiting endogenous cells for all groups albeit with differences in an age-related manner. Analyses of bone tissue formation after 2 and 8 weeks post-treatment show low mineral deposition and reduced number of osteocalcin and tartrate-resistant acid phosphatase (TRAP)-expressing cells in elderly mice.
Tissue engineering strategies that promote tissue repair through recruitment of endogenous cells will have a significant impact in regenerative medicine. Previous studies from our group have shown that biomineralized materials containing calcium phosphate minerals can contribute to neo-bone tissue through recruitment and activation of endogenous cells. In this study, we investigated the effect of age of the recipient on biomaterial-mediated bone tissue repair. Our results show that the age of the recipient mouse had a significant impact on the quality and quantity of the engineered neo-bone tissues, in which delayed/compromised bone tissue formation was observed in older mice. These findings are in agreement with the clinical observations that age of patients is a key factor in bone repair.
新兴研究表明，具有内在骨诱导和骨传导性的合成生物材料作为骨移植物治疗临界骨缺损具有潜在的应用。在这里，生物材料不仅有助于内源性细胞的募集，还支持与骨组织形成和功能相关的细胞活动。虽然这种生物材料介导的原位组织工程非常有吸引力，但这种方法的成功在很大程度上取决于募集细胞的再生潜力，而这预计会随年龄而变化。在这项研究中，我们使用临界尺寸颅缺损作为模型系统，研究了宿主年龄对矿化生物材料介导的骨组织修复的影响。使用不同年龄的小鼠，1 个月大（幼年）、2 个月大（青年）、6 个月大（中年）和 14 个月大（老年）作为接受者。我们的结果表明，生物矿化支架通过募集内源性细胞支持骨组织形成，尽管存在与年龄相关的差异。在治疗后 2 周和 8 周时对骨组织形成的分析表明，老年小鼠的矿物质沉积较少，骨钙素和抗酒石酸酸性磷酸酶（TRAP）表达细胞数量减少。
通过募集内源性细胞促进组织修复的组织工程策略将对再生医学产生重大影响。我们小组的先前研究表明，含有磷酸钙矿物质的生物矿化材料可以通过募集和激活内源性细胞来促进新骨组织的形成。在这项研究中，我们研究了接受者年龄对生物材料介导的骨组织修复的影响。我们的结果表明，接受者小鼠的年龄对工程化新骨组织的质量和数量有显著影响，其中老年小鼠的骨组织形成延迟/受损。这些发现与临床观察结果一致，即患者的年龄是骨修复的关键因素。
