Complete pulpodentin complex regeneration by modulating the stiffness of biomimetic matrix

Tiejun Qu, Junjun Jing, Yinshi Ren, Chi Ma, Jian Q. Feng, Qing Yu, Xiaohua Liu

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Dental caries is one of the most prevalent chronic diseases in all populations. The regeneration of dentinpulp 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 lowstiffness 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 lowand 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 4 weeks. 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.

Original languageEnglish (US)
Pages (from-to)60-70
Number of pages11
JournalActa Biomaterialia
Volume16
Issue number1
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Keywords

  • Dentin
  • Gelatin
  • Pulp
  • Pulpodentin complex
  • Stiffness

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering
  • Molecular Biology

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