Abstract
Silk fibroin (SF) and hyaluronic acid (HA) were crosslinked by horseradish peroxidase (HRP)/H2O2, and 1,4-Butanediol di-glycidyl ether (BDDE), respectively, to produce HA/SF-IPN (interpenetration network) (HS-IPN) hydrogels. HS-IPN hydrogels consisted of a SF strain with a high content of tyrosine (e.g., strain A) increased viscoelastic modules compared with those with low contents (e.g., strain B and C). Increasing the quantities of SF in HS-IPN hydrogels (e.g., HS7-IPN hydrogels with weight ratio of HA/SF, 5:7) increased viscoelastic modules of the hydrogels. In addition, the mean pores size of scaffolds of the model hydrogels were around 38.96 ± 5.05 μm which was between those of scaffolds H and S hydrogels. Since the viscoelastic modulus of the HS7-IPN hydrogel were similar to those of human nucleus pulposus (NP), it was chosen as the model hydrogel for examining the differentiation of human bone marrow-derived mesenchymal stem cell (hBMSC) to NP. The differentiation of hBMSC induced by transforming growth factor β3 (TGF-β3) in the model hydrogels to NP cells for 7 d significantly enhanced the expressions of glycosaminoglycan (GAG) and collagen type II, and gene expressions of aggrecan and collagen type II while decreased collagen type I compared with those in cultural wells. In summary, the model hydrogels consisted of SF of strain A, and high concentrations of SF showed the highest viscoelastic modulus than those of others produced in this study, and the model hydrogels promoted the differentiation of hBMSC to NP cells.
Highlights
Hydrogels can be produced by crosslinking polymers to form interpenetration network (IPN)with varying mechanical properties [1,2] for tissue engineering such as cardiac tissue repairs [3], controlling the fates of stem cells [1], and drug delivery, etc. [4]
Without chemical modifications such as crosslinking of hyaluronic acid (HA) hydrogels, the gels would be disassembled in aqueous environment and lost their mechanical properties which would usually deviate from those of human tissues including nucleus pulposus (NP)
HA network hydrogel was widely fabricated by crosslinking hydroxyl groups of N-acetyl-d-glucosamine (NAG) in HA using the epoxide groups of Butanediol di-glycidyl ether (BDDE) at a high pH condition
Summary
Hydrogels can be produced by crosslinking polymers to form interpenetration network (IPN)with varying mechanical properties [1,2] for tissue engineering such as cardiac tissue repairs [3], controlling the fates of stem cells [1], and drug delivery, etc. [4]. With varying mechanical properties [1,2] for tissue engineering such as cardiac tissue repairs [3], controlling the fates of stem cells [1], and drug delivery, etc. Since hydrogels are highly permeable to nutrients and water-soluble metabolites, they can support cell growth and proliferation which are suitable for tissue engineering (TE). Hydrogels for TE usually consist of synthetic polymers, such as polyurethane and polyvinyl alcohol (PVA) [5,6], or natural polymers, such as HA and collagen [7,8]. HA is a natural glycosaminoglycan with carboxylic groups; it is an important component of the extracellular matrices (ECM) in various tissues and play important roles in cell proliferation and migration [9]. Various methods to prepare HA-based hydrogels including oxidized-HA or methacrylated-HA have been investigated for TE of ECM of NP [11,12,13], respectively
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