title: Synthesis of and in vitro and in vivo evaluation of a novel TGF-β1-SF-CS three-dimensional scaffold for bone tissue engineering.
abstract: The role of transforming growth factor-β1 (TGF-β1) in normal human fracture healing has been previously demonstrated. The objective of the present study was to examine the biocompatibility of TGF-β1-silk fibroin-chitosan (TGF-β1-SF-CS) three-dimensional (3D) scaffolds in order to construct an ideal scaffold for bone tissue engineering. We added TGF-β1 directly to the SF-CS scaffold to construct a 3D scaffold for the first time, to the best of our knowledge, and performed evaluations to determine whether it may have potential applications as a growth factor delivery device. Bone marrow-derived mesenchymal stem cells (BMSCs) were seeded on the TGF-β1-SF-CS scaffolds and the silk fibroin-chitosan (SF-CS) scaffolds. On the TGF-β1‑SF-CS and the SF-CS scaffolds, the cell adhesion rate increased in a time‑dependent manner. Using a Cell Counting Kit-8 (CCK-8) assay and analyzing the alkaline phosphatase (ALP) expression proved that TGF-β1 significantly enhanced the growth and proliferation of BMSCs on the SF-CS scaffolds in a time-dependent manner. To examine the in vivo biocompatibility and osteogenesis of the TGF-β1‑SF-CS scaffolds, the TGF-β1-SF-CS scaffolds and the SF-CS scaffolds were implanted in rabbit mandibles and studied histologically and microradiographically. The 3D computed tomography (CT) scan and histological examinations of the samples showed that the TGF-β1-SF-CS scaffolds exhibited good biocompatibility and extensive osteoconductivity with the host bone after 8 weeks. Moreover, the introduction of TGF-β1 to the SF-CS scaffolds markedly enhanced the efficiency of new bone formation, and this was confirmed using bone mineral density (BMD) and biomechanical evaluation, particularly at 8 weeks after implantation. We demonstrated that the TGF-β1‑SF-CS scaffolds possessed as good biocompatibility and osteogenesis as the hybrid ones. Taken together, these findings indicate that the TGF-β1-SF-CS scaffolds fulfilled the basic requirements of bone tissue engineering, and have the potential to be applied in orthopedic, reconstructive and maxillofacial surgery. Thus, TGF-β1-SF-CS composite scaffolds represent a promising, novel type of scaffold for use in bone tissue engineering.
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Liaoning Institute of Dental Research, Shenyang, Liaoning 110002, P.R. China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Tong
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Liaoning Institute of Dental Research, Shenyang, Liaoning 110002, P.R. China.
authors.forename: Da-Peng
authors.initials: DP
authors.lastname: Xu
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Liaoning Institute of Dental Research, Shenyang, Liaoning 110002, P.R. China.
authors.forename: Zi-Mei
authors.initials: ZM
authors.lastname: Liu
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Liaoning Institute of Dental Research, Shenyang, Liaoning 110002, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Liaoning Institute of Dental Research, Shenyang, Liaoning 110002, P.R. China.
authors.forename: Xu-Kai
authors.initials: XK
authors.lastname: Wang
mesh_terms: D065966:Absorption, Physicochemical; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D001861:Bone Regeneration / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D048271:Chitosan / Q000494:pharmacology*; D005260:Female; D005349:Fibroins / Q000494:pharmacology*; D021621:Imaging, Three-Dimensional; D008297:Male; D008334:Mandible / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009929:Organ Size / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D016062:Porosity; D011817:Rabbits; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*; D014057:Tomography, X-Ray Computed; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D053773:Transforming Growth Factor beta1; D005349:Fibroins; D048271:Chitosan; D000469:Alkaline Phosphatase