In Vivo Evaluation of Decellularized Human Tooth Scaffold for Dental Tissue Regeneration

Abstract

Conventional root canal treatment may result in loss of tooth vitality, which can lead to unfavorable treatment outcomes. Notably, a ceased tooth development of immature permanent teeth with open apices, regeneration of periodontal ligaments (PDL), and pulp is highly expected healing process. For regeneration, the scaffold is one of the critical components that carry biological benefits. Therefore, this study evaluated a decellularized human tooth as a scaffold for the PDL and pulp tissue regeneration. A tooth scaffold was fabricated using an effective decellularization method as reported in previous studies. PDL stem cells (PDLSCs) and dental pulp stem cells (DPSCs) obtained from human permanent teeth were inoculated onto decellularized scaffolds, then cultured to transplant into immunosuppressed mouse. After 9 weeks, PDLSCs and DPSCs that were inoculated onto decellularized tooth scaffolds and cultured in an in vivo demonstrated successful differentiation. In PDLSCs, a regeneration of the cementum/PDL complex could be expected. In DPSCs, the expression of genes related to revascularization and the hard tissue regeneration showed the possibility of pulp regeneration. This study suggested that the potential possible application of decellularized human tooth could be a scaffold in regeneration PDL and pulp tissue along with PDLSCs and DPSCs, respectively, as a novel treatment method.

Influence of extracellular matrix scaffolds on histological outcomes of regenerative endodontics in experimental animal models: a systematic review

“…Different animal models were used in the included studies. The majority used mice [ 38 , 39 , 41 , 42 , 45 , 46 , 48 , 50 , 51 , 53 ] followed by rats [ 43 , 44 , 49 , 52 ], pigs [ 39 , 40 ] and beagle dogs [ 23 , 47 ]. The main source of ECM used was swine [ 23 , 39 , 41 , 47 , 53 ], human [ 46 , 48 , 50 ] or bovine dental pulp [ 43 – 45 ].…”

“…The majority used mice [ 38 , 39 , 41 , 42 , 45 , 46 , 48 , 50 , 51 , 53 ] followed by rats [ 43 , 44 , 49 , 52 ], pigs [ 39 , 40 ] and beagle dogs [ 23 , 47 ]. The main source of ECM used was swine [ 23 , 39 , 41 , 47 , 53 ], human [ 46 , 48 , 50 ] or bovine dental pulp [ 43 – 45 ]. Others used cell-generated ECM [ 38 , 42 ], swine tooth bud [ 40 ], human amniotic membrane [ 49 , 52 ] and rats’ submandibular glands [ 51 ].…”

Advances Focusing on the Application of Decellularized Extracellular Matrix in Periodontal Regeneration

“…The human tooth dECM has also been demonstrated to promote the differentiation of PDLSC, as proved by Ik-Hwan Kim et al [ 31 ]. The cementum/PDL-anchored structures can be regenerated after PDLSC migration as expected, which suggests that decellularized human tooth material may serve as a biological scaffold for PDLSC loading as a novel therapeutic approach for periodontal defects.…”

“…However, more and more research is adopting a multiphasic structural scaffold with multiple chambers [ 28 , 49 , 86 , 93 , 94 , 95 ] in periodontal regeneration, aiming for the entire periodontal regeneration of C, P, and AB [ 96 ]. Most of the research claimed to regenerate entire periodontal tissue with harmonious tissue layers adopted a multi-phrasing scaffold combining bioactive molecules and physical signals [ 28 , 31 , 86 , 93 , 94 ]. Moreover, combinations of extracellular components such as dECM, exosomes, apoptotic extracellular vesicles, and stem cells were also of great potential since this therapy refill the defect area with more of the same components as the original tissue in the first place, and dECM could function as a stem cell carrier as well as promote cell-ECM communication through activation of the signaling pathway for transduction [ 32 ].…”

Creating a Microenvironment to Give Wings to Dental Pulp Regeneration—Bioactive Scaffolds

“…Furthermore, it retains the vascular structure and vascular endothelial growth factor (VEGF) and increases the relative mRNA expression level of angiogenesis markers during the treatment of recellularization [ 54 ]. Conditioned medium made from decellularized scaffolds can ameliorate the proliferation and migration ability of DPSCs, and the animal model of dental pulp regeneration demonstrates ideal results [ 51 , 54 , 55 , 56 , 57 ]. Decellularized pulp matrix also enhanced the odontogenic differentiation ability of DPSCs with high BMP4 expression with the help of recombinant adenovirus [ 58 ].…”