Human Digested Dentin Matrix for Dentin Regeneration and the Applicative Potential in Vital Pulp Therapy

作者全名："Li, Zheng; Zheng, Chengxiang; Jiang, Peiru; Xu, Xiaoqi; Tang, Yin; Dou, Lei"

作者地址："[Li, Zheng; Zheng, Chengxiang; Jiang, Peiru; Xu, Xiaoqi; Dou, Lei] Chongqing Med Univ, Stomatol Hosp 6, Chongqing, Peoples R China; [Li, Zheng; Zheng, Chengxiang; Jiang, Peiru; Xu, Xiaoqi; Dou, Lei] Chongqing Med Univ, Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing, Peoples R China; [Li, Zheng; Zheng, Chengxiang; Jiang, Peiru; Xu, Xiaoqi; Dou, Lei] Chongqing Med Univ, Chongqing Municipal Key Lab Oral Biomed Engn High, Chongqing, Peoples R China; [Tang, Yin] Univ Southern Calif, Herman Ostrow Sch Dent, Los Angeles, CA USA; [Dou, Lei] Western Univ Med Sci, Sch Dent Med, Pomona, CA USA"

通信作者："Dou, L (通讯作者)，Chongqing Med Univ, Affiliated Hosp Stomatol, 426 Song Shi Bei Rd, Chongqing 401147, Peoples R China."

来源：JOURNAL OF ENDODONTICS

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001081145100001

JCR分区：Q1

影响因子：3.5

年份：2023

卷号：49

期号：7

开始页：861

结束页：870

文献类型：Article

关键词：Dental pulp cell; dentin matrix; odontogenic; pulp capping; vital pulp therapy; YAP

摘要："Introduction: Human dentin is a natural acellular matrix with excellent reported biocompatibility. The aim was to fabricate a novel dentin matrix material from human dentin and investigate its applicative potential for vital pulp therapy. Methods: Digested dentin matrix extract (DDME) was fabricated using controlled enzymatic digestion under acidic conditions. The surfaces and biocompatibility of DDME were then investigated, with its effects on the odontogenic differentiation of human dental pulp cells (hDPCs) also studied. The ability of DDME to induce mineralization was assessed in a nude mouse model. The performance of DDME as a pulp capping agent was evaluated in an in situ rat model. The molecular mechanism was verified by mRNA sequencing. Results: A novel type of dentin matrix material with a uniform size of 8 mm was fabricated. DDME had a similar band compared with grinded dentin matrix, with a smaller size, and more uneven surface, as detected by Fourier-transform infrared spectrometer and X-ray photoelectron spectroscopy. DDME at low concentrations did not affect hDPC viability or proliferation, but enhanced runt-related transcription factor 2, dentin matrix acidic phosphoprotein 1, and COL1A1 (collagen type I alpha 1 chain) expression in hDPCs in vitro. DDME was superior to HA-TCP (hydroxyapatite-tricalcium phosphate) in dentin-like mineralized tissue formation after subcutaneous transplantation. In the rat model of pulpotomy, DDME showed visible curative effects. The underlying mechanism may be the inhibition of Hippo signaling following DDME treatment. DDME promoted Yes-associated protein (YAP) 1 nuclear influx, thereby enhancing the expression of DMP-1 (dentin matrix acidic phosphoprotein 1), which was reversed by YAP inhibitor treatment. Conclusions: Human DDME can be used as a biomaterial for dentin regeneration. The combined application of DDME and current pulp capping agents is a potential choice for vital pulp therapy. (J Endod 2023;49:861-870.)"

基金机构：National Natural Science Foundation of China [81800958]; Chongqing Municipal Health Commission [2023GDRC012]

基金资助正文：This study was sponsored by National Natural Science Foundation of China (grant no. 81800958) and Chongqing Municipal Health Commission (grant no. 2023GDRC012).; The authors deny any conflicts of interest related to this study.