Osteostatin-loaded onto mesoporous ceramics improves the early phase of bone regeneration in a rabbit osteopenia model.

Parathyroid hormone-related protein (PTHrP) is an important modulator of bone formation. Recently, we reported that PTHrP (107-111) (osteostatin) coating onto mesoporous ceramics confers osteogenic activity to these materials. Bone repair is dramatically compromised in osteopenia/osteoporosis. Thus, we examined the efficacy of unmodified and organically modified SBA15 ceramics loaded with osteostatin in promoting bone repair in an osteoporotic rabbit model. Osteoporosis was induced in New Zealand rabbits by methylprednisolone administration, and healthy rabbits were used as controls. Tested materials were implanted into a femoral cavitary defect, and animals were sacrificed at 2 weeks post-implantation. At this time, implants were encapsulated by a variable layer of fibrotic tissue with no evidence of inflammation. Similarly to observations in normal rabbits, both types of osteostatin-loaded bioceramics induced tissue regeneration associated with increased staining for PCNA, Runx2, osteopontin, and/or vascular endothelial growth factor in osteoporotic rabbits. Our present findings demonstrate that these osteostatin-bearing bioceramics increase the early repair response not only in normal bone but also in osteoporotic bone after a local injury.

The osteoinductive properties of mesoporous silicate coated with osteostatin in a rabbit femur cavity defect model.

Parathyroid hormone-related protein (PTHrP) is an important regulator of bone formation and remodeling. Our recent findings demonstrate that PTHrP (107-111) (osteostatin) loaded onto silica-based ordered mesoporous SBA15 materials exhibit osteogenic features in osteoblastic cell cultures. We aimed here to elucidate whether these peptide-coated materials might be suitable for promoting bone repair following a cavitary defect in the rabbit femur. Histological examination revealed the absence of significant inflammation or bone resorption within the time of study (4 and 8 weeks) after implantation. At 8 weeks, the peptide-unloaded materials were still separated from the bone marrow by a fibrous cap, which was greatly diminished by the presence of the PTHrP peptide. By using µCT analysis, new bone formation was evident at different distances from the implants, mainly for the latter peptide-loaded biomaterials. This was confirmed by performing immunostaining for different osteoblast markers. Our findings demonstrate that these PTHrP (107-111)-loaded bioceramics significantly improve local bone induction, as compared to that observed with the unloaded material.