title: Morphological differences in BMP-2-induced ectopic bone between solid and crushed hyaluronan hydrogel templates.
abstract: The possibility to affect bone formation by using crushed versus solid hydrogels as carriers for bone morphogenetic protein 2 (BMP-2) was studied. Hydrogels, based on chemical crosslinking between hyaluronic acid and poly(vinyl alcohol) derivatives, were loaded with BMP-2 and hydroxyapatite. Crushed and solid forms of the gels were analyzed both in vitro via a release study using ¹²⁵I radioactive labeling of BMP-2, and in vivo in a subcutaneous ectopic bone model in rats. Dramatically different morphologies were observed for the ectopic bone formed in vivo in the two types of gels, even though virtually identical release profiles were observed in vitro. Solid hydrogels induced formation of a dense bone shell around non-degraded hydrogel, while crushed hydrogels demonstrated a uniform bone formation throughout the entire sample. These results suggest that by crushing the hydrogel, the construct's three-dimensional network becomes disrupted. This could expose unreacted functional groups, making the fragment's surfaces reactive and enable limited chemical fusion between the crushed hydrogel fragments, leading to similar in vitro release profiles. However, in vivo these interactions could be broken by enzymatic activity, creating a macroporous structure that allows easier cell infiltration, thus, facilitating bone formation.
authors: Department of Orthopedics, Uppsala University, Uppsala, Sweden. gry.hulsart@surgsci.uu.se
authors: Gry
authors: G
authors: Hulsart-Billström
authors: Sonya
authors: S
authors: Piskounova
authors: Lars
authors: L
authors: Gedda
authors: Britt-Marie
authors: BM
authors: Andersson
authors: Kristoffer
authors: K
authors: Bergman
authors: Jöns
authors: J
authors: Hilborn
authors: Sune
authors: S
authors: Larsson
authors: Tim
authors: T
authors: Bowden
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D055396:Bone Morphogenetic Protein 2 / Q000493:pharmacokinetics / Q000494:pharmacology*; D002828:Choristoma / Q000139:chemically induced / Q000473:pathology; D004343:Drug Implants / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006820:Hyaluronic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects*; D016062:Porosity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012871:Skin Diseases / Q000139:chemically induced / Q000473:pathology; D013499:Surface Properties
chemical_list: D055396:Bone Morphogenetic Protein 2; D004343:Drug Implants; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D006820:Hyaluronic Acid
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