title: Degradable, antibiotic releasing poly(propylene fumarate)-based constructs for craniofacial space maintenance applications.
abstract: Space maintainers (SMs) used for craniofacial reconstruction function to preserve the void space created upon bone loss and promote soft tissue healing over the defect. Polymethylmethacrylate-based SMs present several drawbacks including implant exposure, secondary removal surgeries, and potential bacterial contamination during implantation. To address these issues, a novel composite material comprising poly(propylene fumarate) (PPF) with N-vinyl pyrrolidone (NVP) as the crosslinking agent, carboxymethylcellulose (CMC) hydrogel as a porogen, and antibiotic loaded poly(lactic-co-glycolic acid) (PLGA) microparticles as antibiotic carriers and porogen was fabricated. CMC was incorporated at 40 wt % to impart rapid porosity while PLGA microparticles were incorporated at 30 or 40 wt % to release either clindamycin or colistin. This study was designed to examine the effects of PPF:NVP ratio, PLGA wt %, and the drug dose on the mass loss, temporal porosity change and drug release kinetics of the composite construct. Mass loss decreased significantly in constructs containing 3:2 PPF:NVP ratio with 30 wt % PLGA (63.2 ± 0.8%) compared to the 2:3 PPF:NVP ratio (80.3 ± 1.0% and 85.3 ± 1.3% for 30 and 40 wt % PLGA content, respectively) at 8 weeks. In formulations with 3:2 PPF:NVP ratio, incorporation of 40 versus 30 wt % PLGA significantly increased the porosity at 8 weeks under accelerated degradation conditions. Constructs released clindamycin or colistin at concentrations above the minimum inhibitory concentration for target pathogens for 45 and 77 days, respectively. This study demonstrates that the composition of PPF/CMC/PLGA constructs can be modulated to achieve properties suitable for craniofacial degradable space maintenance applications.
authors.affiliation: Department of Bioengineering, Rice University, Houston, Texas.
authors.forename: Allan M
authors.initials: AM
authors.lastname: Henslee
authors.forename: Sarita R
authors.initials: SR
authors.lastname: Shah
authors.forename: Mark E
authors.initials: ME
authors.lastname: Wong
authors.forename: Antonios G
authors.initials: AG
authors.lastname: Mikos
authors.forename: F Kurtis
authors.initials: FK
authors.lastname: Kasper
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D002981:Clindamycin / Q000494:pharmacology; D003091:Colistin / Q000494:pharmacology; D005145:Face; D005650:Fumarates / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D008970:Molecular Weight; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011126:Polypropylenes / Q000737:chemistry*; D016062:Porosity; D012886:Skull / Q000187:drug effects*; D013027:Space Maintenance, Orthodontic / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*; D055114:X-Ray Microtomography
chemical_list: D000900:Anti-Bacterial Agents; D005650:Fumarates; D011126:Polypropylenes; C097850:poly(propylene fumarate); D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D002981:Clindamycin; D002266:Carboxymethylcellulose Sodium; D003091:Colistin
keywords: antibiotic release; bone tissue engineering; degradation; poly(propylene fumarate)