In vitro evaluation of photo‐crosslinkable chitosan‐lactide hydrogels for bone tissue engineering

Abstract

Here we report the development and characterization of novel photo-crosslinkable chitosan-lactide (Ch-LA) hydrogels for bone tissue engineering. We synthesized the hydrogels based on Ch, LA, and methacrylic anhydride (MA), and examined their chemical structures, degradation rates, compressive moduli, and protein release kinetics. We also evaluated the cytotoxicity of the hydrogels and delivery efficacy of bone morphogenetic protein-2 (BMP-2) on osteoblast differentiation and mineralization using W-20-17 preosteoblast mouse bone marrow stromal cells and C2C12 mouse myoblast cells. NMR and FTIR revealed that the hydrogels were formed via amidation and esterification between Ch and LA, and methacrylation for photo-crosslinkable networks. Addition of a hydrophobic LA moiety to a hydrophilic Ch chain increased swellability, softness, and degradation rate of the photo-crosslinkable Ch-LA hydrogels. Changes in Ch/LA ratio and UV exposure time significantly affected compressive modulus and protein release kinetics. The photo-crosslinkable Ch-LA hydrogels were not cytotoxic regardless of the composition and UV crosslinking time. Higher alkaline phosphatase activities of both W-20-17 and C2C12 cells were observed in the less-crosslinked hydrogels at day 5. Mineralization was enhanced by sustained BMP-2 release from the hydrogels, but was cell type dependent. This photo-crosslinkable Ch-LA hydrogel is a promising carrier for growth factors.

Novel osteoinductive photo-cross-linkable chitosan-lactide-fibrinogen hydrogels enhance bone regeneration in critical size segmental bone defects

“…In our hydrogel systems, the hydrophilic chitosan backbone molecules and hydrophobic polylactide side chains can form the copolymer networks with both hydrophobic and hydrophilic components, which can be suitable for delivery of variety of drugs regardless of wettability. Furthermore, amide or ester linkages for the branched PLA chains can function as plasticizers internally in the rigid main chain of chitosan [31–32], providing the mechanical flexibility and elasticity of the hydrogel [24]. Another significant advantage of the CLF hydrogel system is that growth factor binding ligands such as fibrinogen can be easily incorporated into the prepolymer solution due to the hydrophilic nature of chitosan.…”

“…This CLF hydrogel was developed based on our previous work on a chitosan-lactide (CL) hydrogel by addition of fibrinogen [24]. Fibrinogen contains a heparin-binding domain, which was used to improve BMP-2 binding affinity [21, 25].…”

Chitosan Hydrogels for Regenerative Engineering

“…Recently, Kim et al developed a photocrosslinked hydrogel made of chitosan-lactide-fibrinogen (CLF) as a delivery system for BMP-2 [100]. Chitosan and lactide in the hydrogel controlled the physiochemical properties of the hydrogel [101]. Fibrinogen, which contains heparin-binding domains, was added to this system to improve BMP-2 binding.…”

Photopolymerized Injectable Water-soluble Maleilated Chitosan/ Poly(ethylene glycol) Diacrylate Hydrogels as Potential Tissue Engineering Scaffolds

“…Photopolymerized injectable hydrogels are extensively investigated for various tissue engineering applications [1,2], primarily due to their unique merits such as direct application to the targets in a minimally invasive manner, spatially-controlled fast gel transition at physiological condition [3], and more importantly, local delivery of growth factors or cells to promote tissue repair rapidly by mimicking natural tissues environments [4]. Several synthetic and natural polymers, such as poly (ethylene glycol) [5], hyaluronic acid [6], alginate [7] and chitosan, have been explored to synthesize photocrosslinked injectable hydrogels.…”