Bone Response to CaP Cement Containing TGF-β1 Loaded Gelatin Microparticles

Objective: Calcium-phosphate (CaP) cements are bone substitutes, which are highly bone compatible. CaP cements are supposed to be degraded and subsequently replaced by bone tissue. The degradation process can be enhanced by creating microporosity in the cement, e.g. by the inclusion of degradable polymeric microparticles. The cement and microparticles have to be degraded while at the same time being replaced by bone. To stimulate this process, the included microparticles can be used for the delivery of a bone repair stimulating growth factor. Therefore, the aim of this study was to investigate the potential of TGF-β1 loaded gelatin microparticles to enhance the regeneration of rabbit femoral defects filled with injectable CaP/gelatin microparticle composites.

Methods: TGF-β1 loaded composites and non-loaded controls were injected in circular defects (4mm in diameter, 6 mm in depth) as created in the femoral condyles of rabbits and were left in place for four, eight, and twelve weeks. The specimens were evaluated mechanically (push-out test) and histologically.

Results: A gradual increase raise in mechanical strength was seen with increasing implantation periods. At four weeks, push-out value of the CP/gelatin composites was 3.7±1.7 MPa, at eight weeks 6.6±1.6 MPa and at twelve weeks 10±2.9 MPa. The CaP/gelatin+TGF-β1 composites showed mechanical strength values of 2.9±0.7 MPa at four weeks, 4.9±3.0 MPa at eight weeks and 9.1±3.6 MPa at twelve weeks. No significant differences were seen between both composite formulations. Histological and histomorphometrical evaluation showed similar results for both composite formulations regarding new bone formation and bone/implant contact. However, TGF-β1 loading of the composites demonstrated a significant effect on composite degradation after twelve weeks of implantation, 3.8±2.3 mm² vs. 7.7±1.7 mm² of remaining surface area.

Conclusions: CaP/gelatin composites show excellent osteogenic properties and a rapid increase in mechanical strength. The addition of TGF-β1 significantly enhances the bone remodeling process.