title: Complete pulpodentin complex regeneration by modulating the stiffness of biomimetic matrix.
abstract: Dental caries is one of the most prevalent chronic diseases in all populations. The regeneration of dentin-pulp tissues (pulpodentin) using a scaffold-based tissue engineering strategy is a promising approach to replacing damaged dental structures and restoring their biological functions. However, the current scaffolding design for pulpodentin regeneration does not take into account the distinct difference between pulp and dentin, therefore, is incapable of regenerating a complete tooth-like pulpodentin complex. In this study, we determined that scaffolding stiffness is a crucial biophysical cue to modulate dental pulp stem cell (DPSC) differentiation. The DPSCs on a high-stiffness three-dimensional (3D) nanofibrous gelatin (NF-gelatin) scaffold had more organized cytoskeletons and a larger spreading area than on a low-stiffness NF-gelatin scaffold. In the same differentiation medium, a high-stiffness NF-gelatin facilitated DPSC differentiation to form a mineralized tissue, while a low-stiffness NF-gelatin promoted a soft pulp-like tissue formation from the DPSCs. A facile method was then developed to integrate the low- and high-stiffness gelatin matrices into a single scaffold (S-scaffold) for pulpodentin complex regeneration. A 4-week in vitro experiment showed that biomineralization took place only in the high-stiffness peripheral area and formed a ring-like structure surrounding the non-mineralized central area of the DPSC/S-scaffold construct. A complete pulpodentin complex similar to natural pulpodentin was successfully regenerated after subcutaneous implantation of the DPSC/S-scaffold in nude mice for 4weeks. Histological staining showed a significant amount of extracellular matrix (ECM) formation in the newly formed pulpodentin complex, and a number of blood vessels were observed in the pulp tissue. Taken together, this work shows that modulating the stiffness of the NF-gelatin scaffold is a successful approach to regenerating a complete tooth-like pulpodentin complex.
authors: Department of Biomedical Sciences, Texas A&M University Baylor College of Dentistry, Dallas, TX 75246, United States; State Key Laboratory of Military Stomatology, Department of Operative Dentistry & Endodontics, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
authors: Tiejun
authors: T
authors: Qu
authors: Department of Biomedical Sciences, Texas A&M University Baylor College of Dentistry, Dallas, TX 75246, United States; State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
authors: Junjun
authors: J
authors: Jing
authors: Department of Biomedical Sciences, Texas A&M University Baylor College of Dentistry, Dallas, TX 75246, United States.
authors: Yinshi
authors: Y
authors: Ren
authors: Department of Biomedical Sciences, Texas A&M University Baylor College of Dentistry, Dallas, TX 75246, United States.
authors: Chi
authors: C
authors: Ma
authors: Department of Biomedical Sciences, Texas A&M University Baylor College of Dentistry, Dallas, TX 75246, United States.
authors: Jian Q
authors: JQ
authors: Feng
authors: State Key Laboratory of Military Stomatology, Department of Operative Dentistry & Endodontics, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China. Electronic address: yuqing@fmmu.edu.cn.
authors: Qing
authors: Q
authors: Yu
authors: Department of Biomedical Sciences, Texas A&M University Baylor College of Dentistry, Dallas, TX 75246, United States. Electronic address: xliu@bcd.tamhsc.edu.
authors: Xiaohua
authors: X
authors: Liu
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D040761:Biomimetic Materials / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003782:Dental Pulp / Q000378:metabolism*; D003804:Dentin / Q000378:metabolism*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008819:Mice, Nude; D057139:Nanofibers / Q000648:ultrastructure; D019919:Prosthesis Implantation; D012038:Regeneration / Q000187:drug effects*; D013234:Stem Cells / Q000166:cytology; D040521:Subcutaneous Tissue / Q000187:drug effects; D054457:Tissue Scaffolds / Q000737:chemistry
keywords: Dentin; Gelatin; Pulp; Pulpodentin complex; Stiffness