Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, PR China; Stomatological Hospital of Chongqing Medical University, Chongqing 401174, PR China.
Stomatological Hospital of Chongqing Medical University, Chongqing 401174, PR China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, PR China.
Acta Biomater. 2023 Jan 15;156:37-48. doi: 10.1016/j.actbio.2022.11.047. Epub 2022 Nov 29.
The sufficient imitation of tissue structures and components represents an effective and promising approach for tissue engineering and regenerative medicine applications. Dental pulp disease is one of the most common oral diseases, although functional pulp regeneration remains challenging. Herein, we propose a strategy that employs hydrogel microspheres incorporated with decellularized dental pulp matrix-derived bioactive factors to simulate a pulp-specific three-dimensional (3D) microenvironment. The dental pulp microenvironment-specific microspheres constructed by this regenerative strategy exhibited favorable plasticity, biocompatibility, and biological performances. Human dental pulp stem cells (hDPSCs) cultured on the constructed microspheres exhibited enhanced pulp-formation ability in vitro. Furthermore, the hDPSCs-microcarriers achieved the regeneration of pulp-like tissue and new dentin in a semi-orthotopic model in vivo. Mechanistically, the decellularized pulp matrix-derived bioactive factors mediated the multi-directional differentiation of hDPSCs to regenerate the pulp tissue by eliciting the secretion of crucial bioactive cues. Our findings demonstrated that a 3D dental pulp-specific microenvironment facilitated by hydrogel microspheres and dental pulp-specific bioactive factors regenerated the pulp-dentin complex and could be served as a promising treatment option for dental pulp disease. STATEMENT OF SIGNIFICANCE: Injectable bioscaffolds are increasingly used for regenerative endodontic treatment. Despite their success related to their ability to load stem cells, bioactive factors, and injectability, conventional bulk bioscaffolds have drawbacks such as ischemic necrosis in the central region. Various studies have shown that ischemic necrosis in the central region can be corrected by injectable hydrogel microspheres. Unfortunately, pristine microspheres or microspheres without dental pulp-specific bioactive factor would oftentimes fail to regulate stem cells fates in dental pulp multi-directional differentiation. Our present study reported the biofabrication of dental pulp-derived decellularized matrix functionalized gelatin microspheres, which contained dental pulp-specific bioactive factors and have the potential application in endodontic regeneration.
组织结构和成分的充分模拟代表了组织工程和再生医学应用的一种有效且有前途的方法。牙髓疾病是最常见的口腔疾病之一，尽管功能性牙髓再生仍然具有挑战性。在此，我们提出了一种策略，该策略使用含有脱细胞牙髓基质衍生生物活性因子的水凝胶微球来模拟特定于牙髓的三维（3D）微环境。通过这种再生策略构建的具有牙髓微环境特异性的微球表现出良好的可塑性、生物相容性和生物学性能。在构建的微球上培养的人牙髓干细胞（hDPSCs）在体外表现出增强的牙髓形成能力。此外，hDPSCs-微载体在体内半原位模型中实现了牙髓样组织和新牙本质的再生。从机制上讲，脱细胞牙髓基质衍生的生物活性因子通过引发关键生物活性信号的分泌，介导 hDPSCs 的多向分化，从而再生牙髓组织。我们的研究结果表明，水凝胶微球和牙髓特异性生物活性因子构建的 3D 牙髓特异性微环境有利于牙髓-牙本质复合体的再生，可以作为牙髓疾病的一种有前途的治疗选择。
可注射生物支架越来越多地用于再生性牙髓治疗。尽管它们在加载干细胞、生物活性因子和可注射性方面取得了成功，但传统的块状生物支架存在诸如中央区域缺血性坏死等缺点。各种研究表明，可注射水凝胶微球可纠正中央区域的缺血性坏死。不幸的是，原始微球或不含牙髓特异性生物活性因子的微球通常无法调节牙髓多向分化中的干细胞命运。我们目前的研究报告了牙髓衍生的脱细胞基质功能化明胶微球的生物制造，该微球含有牙髓特异性生物活性因子，具有在牙髓再生中的潜在应用。
