Mohiuddin Omair A, Campbell Brett, Poche J Nick, Ma Michelle, Rogers Emma, Gaupp Dina, Harrison Mark A A, Bunnell Bruce A, Hayes Daniel J, Gimble Jeffrey M
Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA, United States.
School of Medicine, Tulane University, New Orleans, LA, United States.
Front Bioeng Biotechnol. 2019 Sep 6;7:211. doi: 10.3389/fbioe.2019.00211. eCollection 2019.
Critical-sized bone defects fail to heal and often cause non-union. Standard treatments employ autologous bone grafting, which can cause donor tissue loss/pain. Although several scaffold types can enhance bone regeneration, multiple factors limit their level of success. To address this issue, this study evaluated a novel decellularized human adipose tissue (DAT) hydrogel as an alternative. In this study, DAT hydrogel alone, or in combination with adipose-derived stromal/stem cells (ASC), osteo-induced ASCs (OIASC), and hydroxyapatite were tested for their ability to mediate repair of a critical-sized (3 mm) femoral defect created in C57BL/6 mice. Micro-computed tomography results showed that all DAT hydrogel treated groups significantly enhanced bone regeneration, with OIASC + hydroxyapatite treated group displaying the most robust bone regeneration. Histological analyses revealed that all treatments resulted in significantly higher tissue areas with the relative mineralized tissue area significantly increased at 12 weeks; however, cartilaginous content was lowest among treatment groups with OIASC. Immunohistochemical analyses showed that DAT hydrogel enhanced collagen I and osteopontin expression, while the addition of OIASCs to the hydrogel reduced collagen II levels. Thus, DAT hydrogel promotes bone regeneration in a critical-sized femoral defect model that is further enhanced in the presence of OIASCs and hydroxyapatite.
临界尺寸骨缺损无法自行愈合，常导致骨不连。标准治疗方法采用自体骨移植，这可能会导致供体组织损失/疼痛。尽管有几种类型的支架可以促进骨再生，但多种因素限制了它们的成功程度。为了解决这个问题，本研究评估了一种新型的脱细胞人脂肪组织（DAT）水凝胶作为替代方案。在本研究中，单独测试了DAT水凝胶，或其与脂肪来源的基质/干细胞（ASC）、骨诱导ASC（OIASC）和羟基磷灰石的组合，以评估它们介导修复C57BL/6小鼠中创建的临界尺寸（3毫米）股骨缺损的能力。微型计算机断层扫描结果显示，所有DAT水凝胶治疗组均显著促进了骨再生，其中OIASC + 羟基磷灰石治疗组的骨再生最为显著。组织学分析显示，所有治疗均导致组织面积显著增加，相对矿化组织面积在12周时显著增加；然而，在OIASC治疗组中软骨含量最低。免疫组织化学分析表明，DAT水凝胶增强了I型胶原蛋白和骨桥蛋白的表达，而向水凝胶中添加OIASC则降低了II型胶原蛋白水平。因此，DAT水凝胶在临界尺寸股骨缺损模型中促进骨再生，在存在OIASC和羟基磷灰石的情况下进一步增强。
