Pre-clinical Models of Odontic Analogs by Endogenous Stem Cells Project summary Tooth loss is the most common organ failure. Complete tooth loss in many wildlife species equates to the end of life. For humans, tooth loss negatively impacts one's self-esteem and impairs multiple physiological functions including mastication, digestion and/or speech. In this application that is specifically designed in response to PA-10-009, Bioengineering Research Grants (BRG), we propose to develop odontic analogs based on biomaterial scaffolds in the shape and dimensions of native tooth roots in a preclinical model. Currently, dentures or dental implants are the treatments of choice for patients who are partially or completely edentulous. However, a number of drawbacks are associated with dentures and dental implants, including failure, metal allergy and excessive cost. We demonstrate in our preliminary data that a tooth root analog regenerated with putative periodontal ligament and alveolar bone upon implantation of anatomically correct 3D biomaterial scaffold in vivo. The overall goal of this R01 proposal is to generate proof-of-concept data in a preclinical model that represents an obligatory step for further development of an affordable technology towards eventual clinical applications. As a departure from previous tooth regeneration studies that invariably involve the meritorious approach of stem cell transplantation, the proposed experiments are designed to include two primary innovative approaches. First, all the proposed studies will be based on the homing of host endogenous stem cells by cytotatic cues. No cells will be transplanted. Regeneration by stem cell homing, if proven effective in pre-clinical models and future clinical trials, may circumvent issues such as excessive time and cost in association with ex vivo cell culture, potential contamination and tumoerigenesis. Second, we take a novel approach to determine how physical properties of scaffold biomaterials affect the recruitment and differentiation of endogenous stem/progenitor cells, an approach that has not been investigated in tooth regeneration. If odontic analogs are developed in vivo as a function of various properties of bioscaffolds and without the delivery of cytotactic cues or cells, clinical translation can be further accelerated. These proposed studies in a preclinical model represent the most rigorous translational effort on tooth root regeneration, short of a human clinical trial that can only be conducted after a preclinical study and after FDA and IRB approvals.
Oral diseases negatively affect one's self-esteem and impair multiple physiological functions including mastication, digestion and/or speech. In this proposal, we propose to develop novel odontic analogs to address the current shortage of regenerative dental devices.
|Shah, Bhranti S; Chen, Mo; Suzuki, Takahiro et al. (2017) Pyrintegrin Induces Soft Tissue Formation by Transplanted or Endogenous Cells. Sci Rep 7:36402|
|He, Ling; Zhong, Juan; Gong, Qimei et al. (2017) Treatment of Necrotic Teeth by Apical Revascularization: Meta-analysis. Sci Rep 7:13941|
|Jiang, Nan; Xiang, Lusai; He, Ling et al. (2017) Exosomes Mediate Epithelium-Mesenchyme Crosstalk in Organ Development. ACS Nano 11:7736-7746|
|Jiang, Nan; Chen, Mo; Yang, Guodong et al. (2016) Hematopoietic Stem Cells in Neural-crest Derived Bone Marrow. Sci Rep 6:36411|
|Zhou, Chen; Yang, Guodong; Chen, Mo et al. (2015) Lhx6 and Lhx8: cell fate regulators and beyond. FASEB J 29:4083-91|
|Zhou, Chen; Yang, Guodong; Chen, Mo et al. (2015) Lhx8 mediated Wnt and TGF? pathways in tooth development and regeneration. Biomaterials 63:35-46|
|Hu, Li; Yang, Guodong; Hägg, Daniel et al. (2015) IGF1 Promotes Adipogenesis by a Lineage Bias of Endogenous Adipose Stem/Progenitor Cells. Stem Cells 33:2483-95|
|Xiang, Lusai; Chen, Mo; He, Ling et al. (2014) Wnt5a regulates dental follicle stem/progenitor cells of the periodontium. Stem Cell Res Ther 5:135|
|Jiang, Nan; Zhou, Jian; Chen, Mo et al. (2014) Postnatal epithelium and mesenchyme stem/progenitor cells in bioengineered amelogenesis and dentinogenesis. Biomaterials 35:2172-80|
|Mendelson, Avital; Ahn, Jeffrey M; Paluch, Kamila et al. (2014) Engineered nasal cartilage by cell homing: a model for augmentative and reconstructive rhinoplasty. Plast Reconstr Surg 133:1344-53|
Showing the most recent 10 out of 17 publications