State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, P. R. China.
State Key Laboratory of Oral Diseases, National Engineering Laboratory for Oral Regenerative Medicine, Engineering Research Center of Oral Translational Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, P. R. China.
Adv Healthc Mater. 2023 Nov;12(28):e2300625. doi: 10.1002/adhm.202300625. Epub 2023 Aug 27.
Recent advances in 3D printing offer a prospective avenue for producing transplantable human tissues with complex geometries; however, the appropriate 3D-printed scaffolds possessing the biological compatibility for tooth regeneration remain unidentified. This study proposes a personalized scaffold of multiple bioactivities, including induction of stem cell proliferation and differentiation, biomimetic mineralization, and angiogenesis. A brand-new bioink system comprising a biocompatible and biodegradable polymer is developed and reinforced with extracellular matrix generated from dentin tissue (treated dentin matrix, TDM). Adding TDM optimizes physical properties including microstructure, hydrophilicity, and mechanical strength of the scaffolds. Proteomics analysis reveals that the released proteins of the 3D-printed TDM scaffolds relate to multiple biological processes and interact closely with each other. Additionally, 3D-printed TDM scaffolds establish a favorable microenvironment for cell attachment, proliferation, and differentiation in vitro. The 3D-printed TDM scaffolds are proangiogenic and facilitate whole-thickness vascularization of the graft in a subcutaneous model. Notably, the personalized TDM scaffold combined with dental follicle cells mimics the anatomy and physiology of the native tooth root three months after in situ transplantation in beagles. The remarkable in vitro and in vivo outcomes suggest that the 3D-printed TDM scaffolds have multiple bioactivities and immense clinical potential for tooth-loss therapy.
3D 打印技术的最新进展为制造具有复杂几何形状的可移植人体组织提供了有前景的途径；然而，具有生物相容性的合适的 3D 打印支架仍然无法确定，用于牙齿再生。本研究提出了一种具有多种生物活性的个性化支架，包括诱导干细胞增殖和分化、仿生矿化和血管生成。开发了一种全新的生物墨水系统，包括生物相容性和可生物降解的聚合物，并通过牙本质组织（处理牙本质基质，TDM）产生的细胞外基质进行强化。添加 TDM 可优化支架的物理性能，包括微观结构、亲水性和机械强度。蛋白质组学分析表明，3D 打印 TDM 支架释放的蛋白质与多种生物学过程相关，并相互密切作用。此外，3D 打印 TDM 支架在体外为细胞附着、增殖和分化建立了有利的微环境。3D 打印 TDM 支架具有促血管生成作用，并促进移植物在皮下模型中的全层血管化。值得注意的是，个性化 TDM 支架与牙滤泡细胞结合，在原位移植到比格犬体内三个月后模拟了天然牙根的解剖结构和生理学。显著的体外和体内结果表明，3D 打印 TDM 支架具有多种生物活性，在牙齿缺失治疗方面具有巨大的临床潜力。
