title: Hydroxyapatite-reinforced in situ forming PLGA systems for intraosseous injection.
abstract: In situ forming poly(lactic-co-glycolic acid) (PLGA) implants have not been strongly considered for bone applications because of their poor mechanical properties. Here, in situ forming scaffolds containing hydroxyapatite micro- and nanoparticles were characterized to determine their mechanical properties, injectability, and microarchitecture. Scaffolds were prepared with various concentrations of hydroxyapatite, as well as poly(β-amino ester) microparticles that facilitate drug delivery. Strength was increased threefold, from 2 to 6 MPa, while compressive modulus was improved sixfold, from 24 to 141 MPa, via the addition of 30% nanohydroxyapatite, which provided greater benefits at equivalent concentrations compared to micro-hydroxyapatite. Scaffolds retained a uniformly porous microarchitecture, and hydroxyapatite particles were distributed evenly throughout the PLGA phase. Injectability, determined by the force required to inject 0.5 mL of material within 60 s, remained clinically acceptable at <50 N at 30% w/w hydroxyapatite and up to 10% w/w PBAE microparticles. Ex vivo injections into intact porcine femoral heads increased compressive modulus of trabecular bone from 81 to 180 MPa and strength from 3.5 to 5.9 MPa. This injectable scaffold offers mechanical reinforcement coupled with previously demonstrated drug delivery potential in a single injection for bone-weakening conditions, such as osteonecrosis or osteoporosis.
authors.affiliation: Department of Biomedical Engineering, University of Kentucky, Lexington, Kentucky, 40506.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Fisher
authors.affiliation: nGimat, LLC., Lexington, Kentucky, 40511.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Venugopal
authors.affiliation: Department of Orthopaedic Surgery, Mayo Clinic, Rochester, Minnesota, 55905.
authors.forename: Todd A
authors.initials: TA
authors.lastname: Milbrandt
authors.affiliation: Department of Chemical and Materials Engineering, University of Kentucky, Lexington, Kentucky, 40506.
authors.forename: J Zach
authors.initials: JZ
authors.lastname: Hilt
authors.affiliation: Department of Biomedical Engineering, University of Kentucky, Lexington, Kentucky, 40506.
authors.forename: David A
authors.initials: DA
authors.lastname: Puleo
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000378:metabolism*; D004333:Drug Administration Routes; D006882:Hydroxyapatites / Q000008:administration & dosage*; D019344:Lactic Acid / Q000008:administration & dosage*; D008297:Male; D011100:Polyglycolic Acid / Q000008:administration & dosage*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013552:Swine
chemical_list: D006882:Hydroxyapatites; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: PLGA; hydroxyapatite; in situ forming; injectable; mechanical reinforcement