title: Numerical Simulation of Mass Transfer and Three-Dimensional Fabrication of Tissue-Engineered Cartilages Based on Chitosan/Gelatin Hybrid Hydrogel Scaffold in a Rotating Bioreactor.
abstract: Cartilage tissue engineering is believed to provide effective cartilage repair post-injuries or diseases. Biomedical materials play a key role in achieving successful culture and fabrication of cartilage. The physical properties of a chitosan/gelatin hybrid hydrogel scaffold make it an ideal cartilage biomimetic material. In this study, a chitosan/gelatin hybrid hydrogel was chosen to fabricate a tissue-engineered cartilage in vitro by inoculating human adipose-derived stem cells (ADSCs) at both dynamic and traditional static culture conditions. A bioreactor that provides a dynamic culture condition has received greater applications in tissue engineering due to its optimal mass transfer efficiency and its ability to simulate an equivalent physical environment compared to human body. In this study, prior to cell-scaffold fabrication experiment, mathematical simulations were confirmed with a mass transfer of glucose and TGF-β2 both in rotating wall vessel bioreactor (RWVB) and static culture conditions in early stage of culture via computational fluid dynamic (CFD) method. To further investigate the feasibility of the mass transfer efficiency of the bioreactor, this RWVB was adopted to fabricate three-dimensional cell-hydrogel cartilage constructs in a dynamic environment. The results showed that the mass transfer efficiency of RWVB was faster in achieving a final equilibrium compared to culture in static culture conditions. ADSCs culturing in RWVB expanded three times more compared to that in static condition over 10 days. Induced cell cultivation in a dynamic RWVB showed extensive expression of extracellular matrix, while the cell distribution was found much more uniformly distributing with full infiltration of extracellular matrix inside the porous scaffold. The increased mass transfer efficiency of glucose and TGF-β2 from RWVB promoted cellular proliferation and chondrogenic differentiation of ADSCs inside chitosan/gelatin hybrid hydrogel scaffolds. The improved mass transfer also accelerated a dynamic fabrication of cell-hydrogel constructs, providing an alternative method in tissue engineering cartilage.
authors.affiliation: Shenzhen Key Laboratory for Anti-Ageing and Regenerative Medicine, Health Science Center, Shenzhen University, 3688 Nanhai Avenue, Shenzhen, Guangdong, 518060, China.|State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian, 116024, China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian, 116024, China. Kedongsong@dlut.edu.cn.
authors.forename: Kedong
authors.initials: K
authors.lastname: Song
authors.affiliation: State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian, 116024, China.
authors.forename: Siyu
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Shenzhen Key Laboratory for Anti-Ageing and Regenerative Medicine, Health Science Center, Shenzhen University, 3688 Nanhai Avenue, Shenzhen, Guangdong, 518060, China.
authors.forename: Jinglian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Shenzhen Key Laboratory for Anti-Ageing and Regenerative Medicine, Health Science Center, Shenzhen University, 3688 Nanhai Avenue, Shenzhen, Guangdong, 518060, China.
authors.forename: Lingzhi
authors.initials: L
authors.lastname: Tang
authors.affiliation: Shenzhen Key Laboratory for Anti-Ageing and Regenerative Medicine, Health Science Center, Shenzhen University, 3688 Nanhai Avenue, Shenzhen, Guangdong, 518060, China.
authors.forename: Siyuan
authors.initials: S
authors.lastname: Li
authors.affiliation: State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian, 116024, China.
authors.forename: Jiangli
authors.initials: J
authors.lastname: Fan
authors.affiliation: Burns Research Group, ANZAC Research Institute, University of Sydney, Concord, NSW, 2139, Australia.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Energy and Power Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China. zhaojiaquan85@163.com.
authors.forename: Jiaquan
authors.initials: J
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian, 116024, China. liutq@dlut.edu.cn.
authors.forename: Tianqing
authors.initials: T
authors.lastname: Liu
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000737:chemistry / Q000378:metabolism; D019149:Bioreactors; D002356:Cartilage / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry / Q000494:pharmacology; D020219:Chondrogenesis / Q000187:drug effects; D003198:Computer Simulation; D005780:Gelatin / Q000737:chemistry / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D006801:Humans; D057446:Hydrodynamics; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D046509:Tissue Culture Techniques / Q000379:methods*; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry*; D053781:Transforming Growth Factor beta2 / Q000378:metabolism
chemical_list: D053781:Transforming Growth Factor beta2; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D005780:Gelatin; D048271:Chitosan; D005947:Glucose
keywords: Chitosan/gelatin hybrid hydrogel; Mass transfer efficiency; Rotating wall vessel bioreactor; Static culture; Tissue-engineered cartilage