title: The stiffness of a crosslinked hyaluronan hydrogel affects its chondro-induction activity on hADSCs.
abstract: Matrix stiffness plays an important role in stem cell differentiation. This study reports the synthesis of methacrylated hyaluronan (MeHA) with different degrees of methacrylation, ranging from 15 to 140% per disaccharide unit, which corresponds to a matrix stiffness ranging from 1.5 to 8 KPa. The swelling ratio was inversely proportional to the matrix stiffness, but the water content remained constant at >97% of the hydrogel mass. A fibril-like surface morphology and larger pore size were observed in lyophilized MeHA hydrogel with a lower stiffness. The matrix stiffness also affected the degradability of the MeHA hydrogel, where softer MeHA hydrogels (MeHA15and MeHA30) were completely degraded within 6 days and a stiffer MeHA hydrogel (MeHA140) was able to retain ∼25% of its initial mass after 30 days. Subsequently, the crosslinked MeHA hydrogel was used as a scaffold to encapsulate human adipose-derived stem cells (hADSCs). The embedded cells remained viable and expressed ∼11-fold higher levels of aggrecan and 42-fold higher levels of collagen type II in MeHA140compared with ADSCs cultured in HA-coated wells. In addition, cells grown in MeHA140exhibited the highest rates of glycosaminoglycan and collagen type II synthesis of ∼5 ng/DNA and 0.4 ng/DNA, respectively. Immunofluorescence staining showed an increase of collagen type II synthesis in MeHA65, MeHA85and MeHA140. This study showed that the matrix stiffness of a hydrogel can be modulated by the degree of methacrylation, thus affecting the efficacy of chondrogenesis in hADSCs. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 808-816, 2018.
authors.affiliation: Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Teong
authors.affiliation: Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Shun-Cheng
authors.initials: SC
authors.lastname: Wu
authors.affiliation: Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chien-Mei
authors.initials: CM
authors.lastname: Chang
authors.affiliation: Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Jhen-Wei
authors.initials: JW
authors.lastname: Chen
authors.affiliation: Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Hui-Ting
authors.initials: HT
authors.lastname: Chen
authors.affiliation: Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Orthopaedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Orthopaedics, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Orthopaedics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chung-Hwan
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Orthopaedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Orthopaedics, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Je-Ken
authors.initials: JK
authors.lastname: Chang
authors.affiliation: Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Ho
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D020219:Chondrogenesis; D005109:Extracellular Matrix / Q000737:chemistry*; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry*; D016062:Porosity; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D020100:Hydrogels; D006820:Hyaluronic Acid
keywords: adipose-derived stem cell; chondrogenesis; hyaluronan; hydrogel; matrix stiffness; methacrylation