Treated dentin matrix‐based scaffolds carrying TGF-β1/BMP4 for functional bio-root regeneration

Chen, Jie; Liao, Lijun; Lan, Tingting; Zhang, Zhijun; Gai, Kuo; Huang, Yibing; Chen, Jinlong; Tian, Weidong; Guo, Weihua

doi:10.1016/j.apmt.2020.100742

Cited by 17 publications

(23 citation statements)

References 52 publications

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“…To overcome the low cellular survival and transdifferentiation potential after implantation, various strategies for the pretreatment of intragrafts have been reported, and these strategies mainly include pretreatment with growth factors or cytokines, preconditioning such as hypoxia, and genetic modifications [ 9 ]. Enlightened by the spatial interface gradient from biomaterial scaffolds (TDMs) [ 15 ], this study reports a strategy for pretreating scaffolds and seed cells with antioxidant drugs to modulate the transplant microenvironment and promote the seed cell antioxidant capacity. In this study, we found that rTDM/ rDFCSs/NAC composites displayed a decrease in replacement resorption and an increase in cellular survival and transdifferentiation potency.…”

Section: Discussionmentioning

confidence: 99%

“…Twenty-four hours before transplantation, the rDFCSs and rTDM scaffolds in the NAC-treated group were pretreated with 5 mmol NAC. The permeability of the TDM scaffold allows the sustained release of growth factors through its porous structure to form a concentration gradient at the TDM interface [ 15 ]. To trace the rDFCs in vivo, all the transplanted cells were labelled with green florescent protein (GFP) through viral transduction at an MOI of 40.…”

Section: Methodsmentioning

confidence: 99%

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Improvement of ECM-based bioroot regeneration via N-acetylcysteine-induced antioxidative effects

et al. 2021

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Background The low survival rate or dysfunction of extracellular matrix (ECM)-based engineered organs caused by the adverse effects of unfavourable local microenvironments on seed cell viability and stemness, especially the effects of excessive reactive oxygen species (ROS), prompted us to examine the importance of controlling oxidative damage for tissue transplantation and regeneration. We sought to improve the tolerance of seed cells to the transplant microenvironment via antioxidant pathways, thus promoting transplant efficiency and achieving better tissue regeneration. Methods We improved the antioxidative properties of ECM-based bioroots with higher glutathione contents in dental follicle stem cells (DFCs) by pretreating cells or loading scaffolds with the antioxidant NAC. Additionally, we developed an in situ rat alveolar fossa implantation model to evaluate the long-term therapeutic effects of NAC in bioroot transplantation. Results The results showed that NAC decreased H2O2-induced cellular damage and maintained the differentiation potential of DFCs. The transplantation experiments further verified that NAC protected the biological properties of DFCs by repressing replacement resorption or ankylosis, thus facilitating bioroot regeneration. Conclusions The following findings suggest that NAC could significantly protect stem cell viability and stemness during oxidative stress and exert better and prolonged effects in bioroot intragrafts.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Improvement of ECM-based bioroot regeneration via N-acetylcysteine-induced antioxidative effects

et al. 2021

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“…Thus, 1,25-dihydroxyvitamin D 3 is expected to be used as an active ingredient in oral clinics. For example, as reported in previous studies [24,25], 1,25-dihydroxyvitamin D 3 can be used as an active drug and a biomaterial scaffold to form a bioengineered tooth root or root apex repair scaffold. Through the gradual degradation of the scaffold and the sustained release of 1,25-dihydroxyvitamin D3, root regeneration and root apex restoration are induced.…”

Section: Discussionmentioning

confidence: 93%

Effect of 1,25‐Dihydroxyvitamin D3 on Stem Cells from Human Apical Papilla: Adhesion, Spreading, Proliferation, and Osteogenic Differentiation

Yang

et al. 2021

BioMed Research International

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Currently, it still remains a difficult problem to treat apical insufficiency of young permanent teeth resulted from pulp necrosis or periapical periodontitis. Previous studies have demonstrated that the treatment of revascularization using stem cells from apical papilla (SCAPs) results in increased root length and thickness of traumatized immature teeth and necrotic pulp. In this study, we investigated the role of 1,25-dihydroxyvitamin D3 in regulating the adhesion, spreading, proliferation, and osteogenic differentiation of SCAP, laying the foundation for subsequent clinical drug development. The immature tooth samples were collected in clinical treatment. SCAPs with stable passage ability were isolated and cultured. The multidifferentiation potential was determined by directed induction culture, while the stem cell characteristics were identified by flow cytometry. There were three groups: group A—SCAPs general culture group; group B—SCAPs osteogenesis induction culture group; and group C—SCAPs osteogenesis induction culture+1,25-dihydroxyvitamin D3 group, and the groups were compared statistically. The proliferation of SCAPs in each groups was detected through CCK-8 assay. RT-qPCR was used to detect the transcription levels of Runx2, ALP, Col I, and OCN of SCAPs in each groups. Results exhibited that the isolated SCAPs had multidifferentiation potential and stem cell characteristics. After 24 h culturing, cells in group C spread better than those in groups A and B. The proliferation activity of SCAPs factored by CCK-8 ranked as group C > group B > group A , while the transcription levels of Runx2, ALP, Col I, and OCN leveled as group C > group B > group A . These results suggested that 1,25-dihydroxyvitamin D3 can significantly promote the adhesion, spreading, and proliferation of SACPs and improve the osteogenic differentiation of SCAPs by means of regulating upward the transcription level of osteogenic differentiation marker.

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“…pTDM, similar to the human derived TDM (hTDM), characterized by lax and porous structure on its surface ( Li et al, 2017 ), will be the main source of biological scaffold to provide structural strength to transplant DFC for constructing xenogenic bioroots, considering its superiority in continuous release of the odontogenic differentiation related proteins like DMP-1/DSPP ( Li et al, 2011 ). DMP-1/DSPP is considered to be an important protein in odontogenesis, which regulates cell mineralization ( Chen et al, 2020; Han et al, 2020 ). When DMP-1/DSPP was knocked out, an obvious defect was observed on the surface of dental crown with dentin hypoplasia and tooth surface depression ( Saito et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…In future, porcine derived ECM will be the most widely used bio-scaffold for ECM-based bioengineering transplantation to replace the failing organs and solve the problem of the limited donor source ( Chen et al, 2020; Lan et al, 2021 ). However, the application of xECM-based organ transplantation faces great challenges for the transplanted xenografts are often susceptible to redox imbalance and immune rejection due to their heterologous antigens which greatly aggravate the nonspecific inflammatory response and subsequent overproduction of ROS.…”

Section: Introductionmentioning

confidence: 99%

PPAR-γ activation promotes xenogenic bioroot regeneration by attenuating the xenograft induced-oxidative stress

Lan

et al. 2022

Preprint

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Objectivexenogenic organ transplantation has been considered the most promising strategy in providing possible subtitutes with physiological function of the failing organs as well as solving the problem of insufficient donor sources. However, the xenograft, suffered from immune rejection and ischemia-reperfusion injury (IRI), causes massive ROS expression and the subsequent cell apoptosis, leading to the xenograft failure. Our previous study found a positive role of PPAR-γ in anti-inflammation through its immunomodulation effects, which inspires us to apply PPAR-γ agonist rosiglitazone (RSG) to address survival issue of xenograft with the potential to eliminate the excessive ROS.MethodsXenogenic bioroot was constructed by wrapping the dental follicle cells (DFC) with porcine extracellular matrix (pECM). The hydrogen peroxide (H2O2)-induced DFC was pretreated with RSG to observe its protection on the damaged biological function. Immunoflourescence staining and transmission electron microscope were used to detect the intracellular ROS level. SD rat orthotopic transplantation model and SOD1 knockout mice subcutaneous transplantation model were applied to explore the regenerative outcome of the xenograft.ResultsRSG pretreatment significantly reduced the adverse effects of H2O2 on DFC with decreased intracellular ROS expression and alleviated mitochondrial damage. In vivo results confirmed RSG administration substantially enhanced the host’s antioxidant capacity with reduced osteoclasts formation and increased periodontal ligament like tissue regeneration efficiency, maximumly maintaining the xenograft function.ConclusionsRSG preconditioning could preserve the biological properties of the transplanted stem cells under OS microenvironment and promote organ regeneration by attenuating the inflammatory reaction and OS injury.

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Treated dentin matrix‐based scaffolds carrying TGF-β1/BMP4 for functional bio-root regeneration

Cited by 17 publications

References 52 publications

Improvement of ECM-based bioroot regeneration via N-acetylcysteine-induced antioxidative effects

Improvement of ECM-based bioroot regeneration via N-acetylcysteine-induced antioxidative effects

Effect of 1,25‐Dihydroxyvitamin D3 on Stem Cells from Human Apical Papilla: Adhesion, Spreading, Proliferation, and Osteogenic Differentiation

PPAR-γ activation promotes xenogenic bioroot regeneration by attenuating the xenograft induced-oxidative stress

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