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Hydroxyapatite-reinforced in situ forming PLGA systems for intraosseous injection.

Journal of biomedical materials research. Part A (2014-11-27)
Paul D Fisher, Ganesh Venugopal, Todd A Milbrandt, J Zach Hilt, David A Puleo
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
1-Methyl-2-pyrrolidinone, anhydrous, 99.5%
Sigma-Aldrich
Hydroxyapatite, nanopowder, <200 nm particle size (BET), ≥97%, synthetic
Sigma-Aldrich
Hydroxyapatite, reagent grade, powder, synthetic
Sigma-Aldrich
6-Mercaptohexanoic acid, 90%
Sigma-Aldrich
Hydroxyapatite, puriss., meets analytical specification of Ph. Eur., BP, FCC, E341, ≥90% (calculated on glowed substance)
Sigma-Aldrich
Hydroxyapatite, purum p.a., ≥90% (as Ca3(PO4)2, KT)
Sigma-Aldrich
Hydroxyapatite, Type I, buffered aqueous suspension
Sigma-Aldrich
Calcium phosphate tribasic, 34.0-40.0% Ca basis
Sigma-Aldrich
Hydroxyapatite, nanopowder, <200 nm particle size (BET), contains 5 wt. % silica as dopant, synthetic
Sigma-Aldrich
Hydroxyapatite, nanoparticles, dispersion, 10 wt. % in H2O, <200 nm particle size (BET)
Sigma-Aldrich
Hydroxyapatite, synthetic, 99.8% trace metals basis (excludes Mg)
Sigma-Aldrich
Calcium phosphate tribasic, BioReagent, suitable for plant cell culture, powder