title: Affinity-based growth factor delivery using biodegradable, photocrosslinked heparin-alginate hydrogels.
abstract: Photocrosslinkable biomaterials are promising for tissue engineering applications due to their capacity to be injected and form hydrogels in situ in a minimally invasive manner. Our group recently reported on the development of photocrosslinked alginate hydrogels with controlled biodegradation rates, mechanical properties, and cell adhesive properties. In this study, we present an affinity-based growth factor delivery system by incorporating heparin into photocrosslinkable alginate hydrogels (HP-ALG), which allows for controlled, prolonged release of therapeutic proteins. Heparin modification had minimal effect on the biodegradation profiles, swelling ratios, and elastic moduli of the hydrogels in media. The release profiles of growth factors from this affinity-based platform were sustained for 3weeks with no initial burst release, and the released growth factors retained their biological activity. Implantation of bone morphogenetic protein-2 (BMP-2)-loaded photocrosslinked alginate hydrogels induced moderate bone formation around the implant periphery. Importantly, BMP-2-loaded photocrosslinked HP-ALG hydrogels induced significantly more osteogenesis than BMP-2-loaded photocrosslinked unmodified alginate hydrogels, with 1.9-fold greater peripheral bone formation and 1.3-fold greater calcium content in the BMP-2-loaded photocrosslinked HP-ALG hydrogels compared to the BMP-2-loaded photocrosslinked unmodified alginate hydrogels after 8weeks implantation. This sustained and controllable growth factor delivery system, with independently controllable physical and cell adhesive properties, may provide a powerful modality for a variety of therapeutic applications.
authors: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.
authors: Oju
authors: O
authors: Jeon
authors: Caitlin
authors: C
authors: Powell
authors: Loran D
authors: LD
authors: Solorio
authors: Melissa D
authors: MD
authors: Krebs
authors: Eben
authors: E
authors: Alsberg
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage / Q000494:pharmacology; D002460:Cell Line; D003692:Delayed-Action Preparations / Q000737:chemistry*; D055119:Elastic Modulus; D020723:Glucuronic Acid / Q000737:chemistry; D006493:Heparin / Q000737:chemistry*; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage* / Q000494:pharmacology; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects; D055668:Photochemical Processes
chemical_list: D000464:Alginates; D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D003692:Delayed-Action Preparations; D006603:Hexuronic Acids; D020100:Hydrogels; D036341:Intercellular Signaling Peptides and Proteins; D020723:Glucuronic Acid; D006493:Heparin