Structurally diverse and readily tunable photocrosslinked chondroitin sulfate based copolymers

Abstract

Our group has previously reported on successful biofunctionalization of poly(ethylene glycol diacrylate) (PEGDA) gels using chondroitin sulfate (CS) and improving moduli of methacrylated-CS (MCS) gels using short PEGDA comonomers. Here, we focused on understanding the composition-property relationship of MCS-PEGDA copolymers. By changing concentration, composition, and medium's ionic strength the gels were modified to show a diverse range of properties. Photopolymerized copolymers with >4:1 ratio of one component had compressive moduli of up to 24 times higher and up to 17 times lower swelling degree (q) than those of MCS alone. The increased moduli and lowered q were consistent with the hypothesis that PEGDA improves kinetic chain growth by overcoming the steric hindrances of the macromer. The swelling and moduli of the gels were tuned by changing the ratio of the comonomers. The swelling and moduli of the gels were lowered with presence of salt in solution while the fracture strain increased. These changes were hypothesized to be the result of transition of CS chain conformation from highly extended and non-Gaussian to less extended and Gaussian distribution. The complete understanding of MCS-PEGDA compositionproperty relationship provides a general strategy to tune the moduli or q of polysaccharide-based hydrogels while avoiding undesirable phase separation. V C 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015, 53, 1070-1079 KEYWORDS: biomaterials; copolymers; hydrogels; mechanical properties; photopolymerization INTRODUCTION The mammalian extracellular matrix (ECM) is a multicomponent, hierarchically ordered structure. Chondroitin sulfate (CS) and hyaluronic acid (HA) are two of the main glycosaminoglycans (GAGs) present in the mammalian ECM. Collagen type II, keratan sulfate, and proteins are other major ECM components. Regeneration of the damaged ECM has been the focus of multiple tissue engineering studies. A common strategy is to replace the damaged matrix with naturally available biomimetic materials. An optimal scaffold to mimic the ECM would be made of multiple components to provide the appropriate balance of mechanical properties, water content, solute permeability, and cell interactions.

Chemical Derivatization of Sulfated Glycosaminoglycans

“…Methacrylated CS‐A derivatives 39 and 43 were cross‐linked by photochemical activation of the double bond with use of a UV photoinitiator and 365 nm light irradiation. This photopolymerization was conducted on methacrylated CS‐A both alone and in the presence of a wide number of different synthetic oligomers or polymers containing double bonds, such as oligo(ethylene glycol) diacrylate, poly(vinyl alcohol), poly(ethylene oxide) diacrylate, PEG diacrylate,, PEG dimethacrylate, polyacrylamide, poly( N , N ‐dimethyl acrylamide), poly(2‐dimethylaminoethyl methacrylate), methoxy‐poly(ε‐caprolactone) acrylate, methoxy‐PEG‐poly(ε‐caprolactone)‐acrylate,, and an acrylated pluronic copolymer . Recently, cross‐linking of methacrylated CS has also been accomplished under reaction conditions other than photopolymerization, such as an atom‐transfer radical addition with a bromide‐end‐capped polycaprolactone in the presence of CuBr and bipyridine, an emulsion polymerization initiated by K 2 S 2 O 8 in an oil‐in‐water system, or a “living” free radical reaction assisted by gamma‐ray irradiation without the need for any initiator , .…”

A thermo-responsive and photo-polymerizable chondroitin sulfate-based hydrogel for 3D printing applications

“…Hydrogel systems based on cross-linked CS offer a suitable in vitro platform in which encapsulated cells, particularly chondrocytes and mesenchymal stem cells, can survive, proliferate, as well as produce cartilage-like ECM (Guo et al, 2012;Huang et al, 2015;Ingavle, Dormer, Gehrke, & Detamore, 2012;Sawatjui et al, 2015). Moreover, CS is able to confer desirable mechanical properties to implants (Khanlari, Suekama, Detamore, & Gehrke, 2015;Sawatjui, Damrongrungruang, Leeanansaksiri, Jearanaikoon, & Limpaiboon, 2014;Zhang et al, 2011). As a result, CS is currently one of the main components of several recently developed hybrid scaffolds studied in vitro and in vivo (Kuo, Chen, Hsiao, & Chen, 2015;Liao, Qu, Chu, Zhang, & Qian, 2015;Ni et al, 2015;Wei, Wang, Su, Wang, & Qiu, 2015).…”

Structurally Versatile Glycosaminoglycan Hydrogels for Biomedical Applications

“…However, OEG monoacrylates increased the crosslink efficiency and modulus to a level comparable to those of the difunctional acrylates, which suggests that incorporation of MCS and comonomer functional groups into common kinetic chains is the key crosslinking mechanism in these gels, rather by the linking segment itself. [28,29,36] The importance of this finding is in the ability to control the crosslink density of MCS gels by changing the comonomer length.…”