Antibiotic-releasing porous polymethylmethacrylate/gelatin/antibiotic constructs for craniofacial tissue engineering

Abstract

An antibiotic-releasing porous polymethylmethacrylate (PMMA) construct was developed to maintain the bony space and prime the wound site in the initial step of a two-stage regenerative medicine approach toward reconstructing significant bony or composite craniofacial tissue defects. Porous polymethylmethacrylate (PMMA) constructs incorporating gelatin microparticles (GMPs) were fabricated by the sequential assembly of GMPs, the antibiotic colistin, and a clinically used bone cement formulation of PMMA powder and methylmethacrylate liquid. PMMA/gelatin/antibiotic constructs with varying gelatin incorporation and drug content were investigated to elucidate the relationship between material composition and construct properties (porosity and drug release kinetics). The porosity of PMMA/gelatin/antibiotic constructs ranged between 7.6±1.8–38.4±1.4% depending on the amount of gelatin incorporated and the drug solution added for gelatin swelling. The constructs released colistin over 10 or 14 days with an average release rate per day above 10 µg/ml. The porosity and in vitro colistin release kinetics of PMMA/gelatin/antibiotic constructs were tuned by varying the material composition and fabrication parameters. This study demonstrates the potential of gelatin-incorporating PMMA constructs as a functional space maintainer for both promoting tissue healing/coverage and addressing local infections, enabling better long-term success of the definitive regenerated tissue construct.

Biomechanical characteristics of cement/gelatin mixture for prevention of cement leakage in vertebral augmentation

“…As bending is a combination of compression and tension, it is deduced that gelatin micro-particles might cause weakening in the PMMA tensile strength. Our finding was also supported by previous studies of PMMA/gelatin/antibiotic constructs used for craniofacial tissue materials [20]. It should also be noted that the decrease of the bending strength was detected within a relatively narrower range of particle density and size than what was reported in the literature as our cement mixture was designed to be injectable [20,30,31].…”

“…Gelatin micro-particles could also be mixed with antibiotic or other therapeutic agents to promote regenerated tissue constructs and to achieve local controlled drug release [18][19][20]. The early clinical study showed reduction of 50 % leakage after the gelatin addition [1].…”

Evaluation of antibiotic releasing porous polymethylmethacrylate space maintainers in an infected composite tissue defect model

“…[2] Previous work from our laboratory has utilized particulate delivery systems, such as gelatin and poly(DL-lactic-co-glycolic acid) (PLGA) microparticles, to control the release of antibiotics from porous PMMA-based constructs. [7,8] The porosity of these constructs was generated by using a carboxymethylcellulose or gelatin hydrogel as a porogen, and the resulting porosity allowed for greater cumulative release of antibiotic. [7][8][9][10] In these studies, colistin, a polypeptide antibiotic, was incorporated into either gelatin or PLGA microparticles.…”

“…[7,8] The porosity of these constructs was generated by using a carboxymethylcellulose or gelatin hydrogel as a porogen, and the resulting porosity allowed for greater cumulative release of antibiotic. [7][8][9][10] In these studies, colistin, a polypeptide antibiotic, was incorporated into either gelatin or PLGA microparticles. Colistin was selected due to its efficacy against Acinetobacter baumannii, a commonly multi-drug resistant bacterial strain that has been observed to have increased incidence of infection in traumatic combat wounds [11][12][13][14][15].…”

Bioactive Scaffolds for the Controlled Formation of Complex Skeletal Tissues

“…Two approaches have been mainly used for scaffold bioactivation: GFs can be encapsulated in a selected drug delivery system such as a microsphere or nanoparticle formulation, and these can be incorporated into the scaffolds. Alternatively, GFs might be incorporated directly into the scaffold itself (Holland & Mikos, 2006;Holland et al, 2007;Liu et al, 2010b;Luginbuehl et al, 2004;Shi et al, 2011;Uebersax et al, 2009). For example, IGF-1 has been incorporated into biodegradable poly(lactide-co-glycolide) microspheres and used as a treatment for 10-mm segmental tibial defects in sheep (Meinel et al, 2003).…”