Xenogeneic Bio-Root Prompts the Constructive Process Characterized by Macrophage Phenotype Polarization in Rodents and Nonhuman Primates

• Published in: Advanced healthcare materials Vol. 6; no. 5
• Main Authors: Li, Hui, Sun, Jingjing, Li, Jie, Yang, Hefeng, Luo, Xiangyou, Chen, Jinlong, Xie, Li, Huo, Fangjun, Zhu, Tian, Guo, Weihua, Tian, Weidong
• Format: Journal Article
• Language: English
• Published: Germany 01.03.2017
• Subjects: Animals; Dental Implants; Dental Pulp - metabolism; Macaca mulatta; Macrophages - metabolism; Rats; Rats, Sprague-Dawley; Swine; Tooth Root; macrophage polarization; treated dentin matrix; tissue remodeling; xenogeneic bioengineered tooth root (bio-root)
• ISSN: 2192-2659
• DOI: 10.1002/adhm.201601112

Tissue or organ regeneration using xenogeneic matrices is a promising approach to address the shortage of donor matrices for allotransplantation. Success of such approach has been demonstrated to correlate with macrophage-mediated fibrotic homeostasis and tissue remodeling. The previous studies have demonstrated that treated dentin matrix (TDM) could be a suitable bioactive substrate for allogeneic tooth root regeneration. This study constructed xenogeneic bioengineered tooth root (bio-root) via a combination of porcine TDM (pTDM) with allogeneic dental follicle cells (DFCs). Macrophage phenotypes are used to evaluate the remodeling process of xenogeneic bio-roots in vitro and in vivo. pTDM can facilitate odontoblast differentiation of human derived DFCs. Xenogeneic bio-roots in rat subcutaneous tissue prompt constructive response via M1 macrophage infiltration during early postimplantation stages and increase restorative M2 phenotype at later stages. After implantation of bio-roots into jaws of rhesus monkeys for six months, periodontal ligament-like fibers accompanied by macrophage polarization are observed, which are positive for COL-1, Periostin, βIII-tubulin and display such structures as fibroblasts and blood vessels. The reconstructed bio-root possesses biomechanical properties for the dissipation of masticatory forces. These results support that xenogeneic bio-root could maintain fibrotic homeostasis during remodeling process and highlight the potential application of xenogeneic matrices in regenerative medicine.