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Sustaining Antibiotic Release from a Poly(methyl methacrylate) Bone-Spacer.

ABSTRACT: One of the challenges in using a bone-spacer to cure infection is the fabrication of a material that can continuously release required antibiotics at effective concentrations for at least 4-6 weeks. Poly(methyl methacrylate) (PMMA) impregnated with antibiotics is one of the popularly used bone-spacer materials. Currently, improved sustained release of hydrophobic and hydrophilic antibiotics is needed for this material. Here, hydrophilic vancomycin (VAN) was encapsulated into calcium citrate (CC) particles and natural rice granules, and hydrophobic erythromycin (ERY) was encapsulated into ethyl cellulose and poly(lactic-co-glycolic acid) particles. The four antibiotic-loaded particles were each incorporated into the PMMA cement. The two unencapsulated drugs and all four drug-loaded particles distributed well in the obtained composites. PMMA composited with VAN-loaded CC showed prolonged VAN release at an effective concentration for more than 40 days, but the composite possessed lesser compressive strength than the PMMA with no drug. PMMA composited with unencapsulated ERY showed a better sustainment of drug release than those composited with encapsulated ERY. VAN elution from the VAN-CC-PMMA did not significantly affect the compressive strength of the material, whereas ERY elution from the ERY-PMMA composite significantly decreased the material's mechanical strength.

SUBMITTER: Oungeun P

PROVIDER: S-EPMC6751690 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Sustaining Antibiotic Release from a Poly(methyl methacrylate) Bone-Spacer.

Oungeun Pongpat P Rojanathanes Rojrit R Pinsornsak Piya P Wanichwecharungruang Supason S

ACS omega 20190903 12

One of the challenges in using a bone-spacer to cure infection is the fabrication of a material that can continuously release required antibiotics at effective concentrations for at least 4-6 weeks. Poly(methyl methacrylate) (PMMA) impregnated with antibiotics is one of the popularly used bone-spacer materials. Currently, improved sustained release of hydrophobic and hydrophilic antibiotics is needed for this material. Here, hydrophilic vancomycin (VAN) was encapsulated into calcium citrate (CC) ...[more]

PMID: 31552325

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Project description:Rationale: Poly (methyl methacrylate) (PMMA) bone cement is one of the most commonly used biomaterials for augmenting/stabilizing osteoporosis-induced vertebral compression fractures (OVCFs), such as percutaneous vertebroplasty (PVP) and balloon kyphoplasty (BKP). However, its clinical applications are limited by its poor performance in high compressive modulus and weak bonding to bone. To address these issues, a bioactive composite bone cement was developed for the treatment of osteoporotic vertebral compression fractures, in which mineralized collagen (MC) was incorporated into the PMMA bone cement (MC-PMMA). Methods: The in vitro properties of PMMA and MC-PMMA composite bone cement were determined, including setting time, compressive modulus, adherence, proliferation, and osteogenic differentiation of rat bone mesenchymal stem cells. The in vivo properties of both cements were evaluated in an animal study (36 osteoporotic New Zealand female rabbits divided equally between the two bone cement groups; PVP at L5) and a small-scale and short-term clinical study (12 patients in each of the two bone cement groups; follow-up: 2 years). Results: In terms of value for PMMA bone cement, the handling properties of MC-PMMA bone cement were not significantly different. However, both compressive strength and compressive modulus were found to be significantly lower. In the rabbit model study, at 8 and 12 weeks post-surgery, bone regeneration was more significant in MC-PMMA bone cement (cortical bone thickness, osteoblast area, new bone area, and bone ingrowth %; each significantly higher). In the clinical study, at a follow-up of 2 years, both the Visual Analogue Score and Oswestry Disability Index were significantly reduced when MC-PMMA cement was used. Conclusions: MC-PMMA bone cement demonstrated good adaptive mechanical properties and biocompatibility and may be a promising alternative to commercial PMMA bone cements for the treatment of osteoporotic vertebral fractures in clinical settings. While the present results for MC-PMMA bone cement are encouraging, further study of this cement is needed to explore its viability as an ideal alternative for use in PVP and BKP.

Project description:Powder-liquid poly (methyl methacrylate) (PMMA) bone cements are widely utilized for augmentation of bone fractures and fixation of orthopedic implants. These cements typically have an abundance of beneficial qualities, however their lack of bioactivity allows for continued development. To enhance osseointegration and bioactivity, calcium phosphate cements prepared with hydroxyapatite, brushite or tricalcium phosphates have been introduced with rather unsuccessful results due to increased cement viscosity, poor handling and reduced mechanical performance. This has limited the use of such cements in applications requiring delivery through small cannulas and in load bearing. The goal of this study is to design an alternative cement system that can better accommodate calcium-phosphate additives while preserving cement rheological properties and performance. In the present work, a number of brushite-filled two-solution bone cements were prepared and characterized by studying their complex viscosity-versus-test frequency, extrusion stress, clumping tendency during injection through a syringe, extent of fill of a machined void in cortical bone analog specimens, and compressive strength. The addition of brushite into the two-solution cement formulations investigated did not affect the pseudoplastic behavior and handling properties of the materials as demonstrated by rheological experiments. Extrusion stress was observed to vary with brushite concentration with values lower or in the range of control PMMA-based cements. The materials were observed to completely fill pre-formed voids in bone analog specimens. Cement compressive strength was observed to decrease with increasing concentration of fillers; however, the materials exhibited high enough strength for consideration in load bearing applications. The results indicated that partially substituting the PMMA phase of the two-solution cement with brushite at a 40% by mass concentration provided the best combination of the properties investigated. This alternative material may find applications in systems requiring highly injectable and viscous cements such as in the treatment of spinal fractures and bone defects.

Project description:Bone tissue engineering strategies have been developed to address the limitations of the current gold standard treatment options for bone-related disorders. These systems consist of an engineered scaffold that mimics the extracellular matrix and provides an architecture to guide the natural bone regeneration process, and incorporated growth factors that enhance cell recruitment and ingress into the scaffold and promote the osteogenic differentiation of stem cells and angiogenesis. In particular, the osteogenic growth factor bone morphogenetic protein 2 (BMP-2) has been widely studied as a potent agent to improve bone regeneration. A key challenge in growth factor delivery is that the growth factors must reach their target sites without losing bioactivity and remain in the location for an extended period to effectively aid in the formation of new bone. Protein incorporation into nanoparticles can both protect protein bioactivity and enable its sustained release. In this study, a poly(methyl methacrylate-co-methacrylic acid) nanoparticle-based system was synthesized incorporating a custom poly(ethylene glycol) dimethacrylate crosslinker. It was demonstrated that the nanoparticle degradation rate can be controlled by tuning the number of hydrolytically degradable ester units along the crosslinker. We also showed that the nanoparticles had high affinity for a model protein for BMP-2, and optimal conditions for maximum protein loading efficiency were elucidated. Ultimately, the proposed system and its high degree of tunability can be applied to a wide range of growth factors and tissue engineering applications. Impact Statement In this study, we developed a novel method of synthesizing nanoparticles with tunable degradation rates through the incorporation of a custom synthesized, hydrolytically degradable crosslinker. In addition, we demonstrated the affinity of the synthesized nanoparticles for a model protein for bone morphogenetic protein 2 (BMP-2). The tunability of these nanoparticles can be used to develop complex tissue engineering systems, for example, for the delivery of multiple growth factors involved at different stages of the bone regeneration process.

Dataset Information

Sustaining Antibiotic Release from a Poly(methyl methacrylate) Bone-Spacer.

Publications

Sustaining Antibiotic Release from a Poly(methyl methacrylate) Bone-Spacer.

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