Drug Delivery from Space-Making Calcium Sulfate/Poly(β-amino ester) Hydrogel Composites

Objective: Calcium sulfate (CS) composites are being developed for controlled delivery of osteogenic agents through direct loading of CS or biodegradable hydrogel (HG) particles while providing a regenerative chamber to promote vertical bone regeneration.

Method: Blank, 1%wt. and 10%wt. HG-particle (150-250μm) CS-composites were fabricated. Destructive mass loss testing was performed to understand CS dissolution in the presence of embedded HG-particles compared to CS alone.  Release kinetics and controllability were studied using lysozyme as a model growth factor directly loaded in CS and in HG-particles embedded in CS. To study the composites’ delivery versatility, a preliminary release study using simvastatin directly loaded in CS was conducted.  Lysozyme and simvastatin release was measured using BCA assays and UV spectroscopy, respectively.

Result: The rates of CS dissolution via surface erosion were consistent with one another, demonstrating that the amount of HG-particles loaded did not have a significant effect.  The 10%wt.-HG (286μg lysozyme) and the 1%wt.-HG (30.7μg lysozyme) loaded composites exhibited zero-order release, whereas samples with directly loaded protein showed burst release, signifying a near-surface segregation of protein.  While hydrogel loading with protein aided in its controlled release, simvastatin zero-order release by direct loading alone.

Conclusion: CS composites containing biodegradable hydrogel particles for delivering osteogenic biomolecules have potential use as scaffolds for vertical bone augmentation.  The hydrogel loading-independence of composite degradation may allow for tuning to provide a sustained delivery of drug to stimulate bone regeneration.  Composite studies using lysozyme as a model growth factor showed promising results for sustained release of protein.  Utilizing both hydrogel and direct loadings could allow greater tailoring of the delivery system to optimize bone regeneration.  The introduction of multiple osteogenic agents could further advance delivery versatility of CS-composites having a potential additive or even a synergistic effect on bone augmentation. This work was supported by the NIH (DE019645).