title: Combination of aligned PLGA/Gelatin electrospun sheets, native dental pulp extracellular matrix and treated dentin matrix as substrates for tooth root regeneration.
abstract: In tissue engineering, scaffold materials provide effective structural support to promote the repair of damaged tissues or organs through simulating the extracellular matrix (ECM) microenvironments for stem cells. This study hypothesized that simulating the ECM microenvironments of periodontium and dental pulp/dentin complexes would contribute to the regeneration of tooth root. Here, aligned PLGA/Gelatin electrospun sheet (APES), treated dentin matrix (TDM) and native dental pulp extracellular matrix (DPEM) were fabricated and combined into APES/TDM and DPEM/TDM for periodontium and dental pulp regeneration, respectively. This study firstly examined the physicochemical properties and biocompatibilities of both APES and DPEM in vitro, and further investigated the degradation of APES and revascularization of DPEM in vivo. Then, the potency of APES/TDM and DPEM/TDM in odontogenic induction was evaluated via co-culture with dental stem cells. Finally, we verified the periodontium and dental pulp/dentin complex regeneration in the jaw of miniature swine. Results showed that APES possessed aligned fiber orientation which guided cell proliferation while DPEM preserved the intrinsic fiber structure and ECM proteins. Importantly, both APES/TDM and DPEM/TDM facilitated the odontogenic differentiation of dental stem cells in vitro. Seeded with stem cells, the sandwich composites (APES/TDM/DPEM) generated tooth root-like tissues after being transplanted in porcine jaws for 12 w. In dental pulp/dentin complex-like tissues, columnar odontoblasts-like layer arranged along the interface between newly-formed predentin matrix and dental pulp-like tissues in which blood vessels could be found; in periodontium complex-like tissues, cellular cementum and periodontal ligament (PDL)-like tissues were generated on the TDM surface. Thus, above results suggest that APES and DPEM exhibiting appropriate physicochemical properties and well biocompatibilities, in accompany with TDM, could make up an ECM microenvironment for tooth root regeneration, which also offers a strategy for complex tissue or organ regeneration.
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China; National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China; Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China; National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China; Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China; National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China; Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China; National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China; Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China; National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China; Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China.
authors.forename: Xiangyou
authors.initials: X
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China; National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China; Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China.
authors.forename: Xuexin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China; National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China.
authors.forename: Lian
authors.initials: L
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China; National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China.
authors.forename: Zongting
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China; National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China.
authors.forename: Mei
authors.initials: M
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China; National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China; Department of Pedodontics, West China College of Stomatology, Sichuan University, No.14, 3rd Section, Renmin South Road, Chengdu, 610041, PR China. Electronic address: guoweihua943019@163.com.
authors.forename: Weihua
authors.initials: W
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China; National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China; Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, PR China. Electronic address: drtwd@sina.com.
authors.forename: Weidong
authors.initials: W
authors.lastname: Tian
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D003782:Dental Pulp / Q000737:chemistry* / Q000378:metabolism; D003804:Dentin / Q000737:chemistry* / Q000378:metabolism; D005780:Gelatin / Q000737:chemistry* / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry* / Q000378:metabolism; D008819:Mice, Nude; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000378:metabolism; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012038:Regeneration; D013552:Swine; D054457:Tissue Scaffolds / Q000737:chemistry*; D014092:Tooth Root / Q000166:cytology / Q000502:physiology*
chemical_list: D001672:Biocompatible Materials; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005780:Gelatin
keywords: Decellularization; Electrospun sheet; Extracellular matrix; Regeneration; Tooth root