Synthesis and characterization of osteoinductive photocurable scaffolds: A tissue engineering approach to enhance bone regeneration.

摘要

Synthetic bone graft materials that form directly in the body via a photoinitiated polymerization may provide a future alternative to current treatment options for bone defects in the musculoskeletal system. Photoinitiated polymerizations are very rapid and form 3-dimensional structures on a clinically acceptable timescale, are readily controlled through changes in the initiation conditions, and are able to polymerize under physiological temperatures and in the presence of body fluids without using potentially toxic solvents. These advantages suggest that photopolymerization is a promising technique to in situ form orthopaedic biomaterials, but the photopolymerization of thick networks is extremely complex due to factors such as light attenuation with sample depth. Thus, experimental approaches were used to investigate network conversion, temperature rises, and structural heterogeneities at various depths during reaction to demonstrate the photopolymerization of thick biomaterials employing appropriate initiation conditions.; Photopolymerized networks formed from novel multifunctional lactic acid based oligomers were synthesized and characterized in this thesis and determined to have controllable physical properties (i.e., degradation and mechanics), osteconductive properties similar to tissue culture polystyrene, and only a mild inflammatory response when implanted in the dorsum of adult rats. When implanted in a critical-sized cranial defect with osteoinductive growth factors, bone regeneration increased substantially in the scaffolds. All of the scaffolds had significantly higher radiopacity than untreated control defects 9 weeks after implantation, and thus, show great promise in the realm of tissue regeneration.; Injectable and photopolymerizable poly(ethylene glycol) based hydrogel networks were also investigated to elicit their potential as a synthetic bone graft material. When growth factors were delivered from the hydrogel networks, the in vitro differentiation of primary rat calvarial osteoblasts was enhanced, and ectopic bone tissue was formed in the dorsum of rats. Osteoblasts encapsulated in the hydrogels survived the photoencapsulation process and remained viable in cultures up to 4 weeks. When an adhesive peptide was tethered to the network, both the attachment and cytoskeleton organization of osteoblasts on hydrogel surfaces were enhanced in addition to augmented mineralization and gene expression by photoencapsulated osteoblasts.