Evaluation of Strontium-Containing PCL-PDIPF Scaffolds for Bone Tissue Engineering: In Vitro and In Vivo Studies.

Bone tissue engineering (BTE) has the general objective of restoring and improving damaged bone. A very interesting strategy for BTE is to combine an adequate polymeric scaffold with an osteoinductive compound. Strontium is a divalent cation that can substitute calcium in hydroxyapatite and induce both anabolic and anti-catabolic effects in bone. On the other hand, systemic increases in Sr2+ levels can provoke adverse cardiovascular effects. In the present study we have developed a compatibilized blend of poly-ε-caprolactone (PCL) and polydiisopropyl fumarate (PDIPF) enriched with 1% or 5% Sr2+ and evaluated the applicability of these biomaterials for BTE, both in vitro and in vivo. In vitro, whereas Blend + 5% Sr2+ was pro-inflammatory and anti-osteogenic, Blend + 1% Sr2+ released very low quantities of the cation; was not cytotoxic for cultured macrophages; and showed improved osteocompatibility when used as a substratum for primary cultures of bone marrow stromal cells. In vivo, implants with Blend + 1% Sr2+ significantly increased bone tissue regeneration and improved fibrous bridging (vs. Blend alone), while neither inducing a local inflammatory response nor increased serum levels of Sr2+. These results indicate that our compatibilized blend of PCL-PDIPF enriched with 1% Sr2+ could be useful for BTE.

Multi-Scale Approach for the Evaluation of Bone Mineralization in Strontium Ranelate-Treated Diabetic Rats.

Long-term diabetes mellitus can induce osteopenia and osteoporosis, an increase in the incidence of low-stress fractures, and/or delayed fracture healing. Strontium ranelate (SrR) is a dual-action anti-osteoporotic agent whose use in individuals with diabetic osteopathy has not been adequately evaluated. In this study, we studied the effects of an oral treatment with SrR and/or experimental diabetes on bone composition and biomechanics. Young male Wistar rats (half non-diabetic, half with streptozotocin/nicotinamide-induced diabetes) were either untreated or orally administered 625 mg/kg/day of SrR for 6 weeks. After sacrifice, femora from all animals were evaluated by a multi-scale approach (X-ray diffraction, Fourier transform infrared spectroscopy, inductively coupled plasma optical-emission spectrometry, static histomorphometry, pQCT, and mechanical testing) to determine chemical, crystalline, and biomechanical properties. Untreated diabetic animals (versus untreated non-diabetic) showed a decrease in femoral mineral carbonate content, in cortical thickness and BMC, in trabecular osteocyte density, in maximum load supported at rupture and at yield point, and in overall toughness at mid-shaft. Treatment of diabetic animals with SrR further affected several parameters of bone (some already impaired by diabetes): crystallinity index (indicating less mature apatite crystals); trabecular area, BMC, and vBMD; maximum load at yield point; and structural elastic rigidity. However, SrR was also able to prevent the diabetes-induced decreases in trabecular osteocyte density (completely) and in bone ultimate strength at rupture (partially). Our results indicate that SrR treatment can partially but significantly prevent some bone structural mechanical properties as previously affected by diabetes, but not others (which may even be worsened).