Bioerodible calcium sulfate/poly(β-amino ester) hydrogel composites

Abstract

The capacity to quickly regenerate or augment bone lost as a result of resorption is crucial to ensure suitable application of prosthetics for restoring masticatory function. Calcium sulfate hemihydrate (CS)-based bone graft substitute composites containing poly(β-amino ester) (PBAE) biodegradable hydrogel particles were developed to act as a ‘tenting’ barrier to soft tissue infiltration, potentially providing adequate space to enable vertical bone regeneration. CS has long been recognized as an osteoconductive biomaterial with an excellent reputation as a biocompatible substance. Composite samples were fabricated with varying amounts (1 or 10 wt%) and sizes (53–150 or 150–250 µm) of gel particles embedded in CS. The swelling and degradation rates of PBAE gels alone were rapid, resulting in complete degradation in less than 24 hours, an important characteristic to aid in controlled release of drug. MicroCT images revealed a homogeneous distribution of gel particles within the CS matrix. All CS samples degraded via surface erosion, with the amount of gel particles (i.e., 10 wt% gel particles) having only a small, but significant, effect on the dissolution rate (4% vs. 5% per day). Compression testing determined that the amount, but not the size, of gel particles had a significant effect on the overall strength of the composites. As much as a 75% drop in strength was seen with a 10 wt% loading of particles. A pilot study using PBAE particles loaded with the multipotential drug curcumin demonstrated sustained release of drug from CS composites. By adjusting the amount and/or size of the biodegradable gel particles embedded in CS, mechanical strength and degradation rates of the composites, as well as the drug release kinetics, can be tuned to provide sufficient, multi-functional ‘space-making’ bone grafting substitutes.

Drug release from calcium sulfate-based composites

“…20,32 To review, polyethylene glycol (PEG) 400 diacrylate (Polysciences, Inc., Warrington, PA) and isobutylamine (Sigma-Aldrich, St. Louis, MO) were combined in a 1.2:1 molar ratio and placed in a flask partially submerged in a silicon oil bath pre-heated to 85°C. The reaction mixture was continuously stirred for 48 hr and then removed from the heat.…”

“…20 Briefly, control (drug- and HG-free) CS samples were made by thoroughly mixing 1 g of CS powder and 800 µL of deionized (DI) water in 3 mL syringes fitted with blunt-tipped needles. The slurry was loaded into a custom Teflon mold having a diameter of 4.7 mm and a height of 6.5 mm and allowed to set at 43°C for 24 hr.…”

“…The synthetic bone graft substitute needs to be biocompatible, osteoconductive to help create a secure bond with the surrounding host tissue, and mechanically stable to ensure that vertical augmentation can be achieved without collapse. 20–22 Calcium sulfate (CS) hemihydrate has an excellent reputation as a biocompatible and osteoconductive substance. 16,23–27 In vivo, calcium sulfate becomes osteogenic in the presence of bone and is completely absorbed without inducing a significant inflammatory response.…”

“…32,34,35 Previous research has shown that PBAE particles can be homogeneously embedded into a CS matrix, which may allow further control over the release of drug from these particles as the CS matrix erodes. 20 …”

“…20 Because candidate bioactive agents, ranging from growth factor to intracellular signaling molecule, will differ in their structure, stability, and mode of action, a larger hydrophilic protein and a smaller hydrophobic molecule were evaluated to demonstrate that a range of osteogenic drugs could be released from the composites, either loaded in hydrogel particles or directly loaded into the CS matrix. Having the ability to deliver a wide range of osteogenic agents would allow for the devices to be tuned based on patient needs.…”