Fumarate/PCL composite based scaffolds with strontium for regeneration of bone tissue

TORRES ML; LINO A; MCCARTHY AD; FERNANDEZ JM

Rosario

Congreso; VIII Congreso Latinoamericano de Órganos Artificiales y Biomateriales, COLAOB 2014; 2014

There are some bone lesions where bone cannot repair completely on its own. The therapies currently used, such as use of implants or grafts, have several disadvantages due to low availability of donor grafts, implant osseointegration problems and high costs for the health care system. To overcome these problems, Bone Tissue Engineering (BTE) proposes to use different materials that can be useful as scaffolds for growth of new bone tissue. These scaffolds must guide tissue repair before being removed by degradation. Our group has previously developed and characterized various materials that could be applied in BTE. One is a compatibilized blend between polyester (poly-ε-caprolactone, PCL) and polyfumarate (poly diisopropyl fumarate, PDIPF). This blend showed better biocompatibility than the respective homopolymers when bone marrow osteoprogenitor cells were cultured. In addition, it showed non toxicity. Bone loss and osteoporosis can be caused by age-related estrogen deficiency or can be secondary to metabolic diseases such as diabetes mellitus. Strontium ranelate (SR) is a drug with both anti-catabolic and anabolic action on bone, and is used as a treatment for post-menopausal osteoporosis. Previously, we have demonstrated that bone microarchitecture improves substantially in rats treated with SR. It is due to an increase in osteoblast activity and an inhibition of osteoclast activity. The goal of the present work was to develop a PDIPF-PCL polymeric scaffold containing strontium (Sr), in order to obtain a matrix that could guide bone repair and, simultaneously, could function as a drug delivery system. For this, membranes of PCL homopolymer and PDIPF-PCL blend (with and without Sr) were obtained by the method of solvent casting. Basically, the polymers were dissolved in chloroform and then poured into a petri dish, allowing the solvent to evaporate until constant weight. After sterilizing the membranes by UV, rat bone marrow progenitor cells were grown in an osteogenic medium (DMEM + 10 % fetal bovine serum with β glycerophosphate and ascorbic acid). After 14 days of culture in these conditions, the cells were lysed with Triton x100 and the biocompatibility of the membranes was evaluated by measuring the activity of the enzyme alkaline phosphatase (ALP) as a parameter of osteogenic differentiation. Furthermore, the proliferation of these cells on different membranes was assessed using the MTT method during different periods. Sr release into the culture medium was evaluated using a flame photometer. Blend released more Sr than PCL (115 % ± 3 % respect PCL during first weeks and 134 % ± 7 %respect to PCL after second week of culture). In conjunction with the release of Sr, our results demonstrate that the presence of Sr in the membrane induces an increase in cellular ALP levels (148% ± 7% Blend and 125% ± 3% PCL versus membranes without Sr). In addition, the ALP was higher in cells grown on Blend + Sr than PCL + Sr (131 % respect to PCL + Sr). However, there were no significant differences in cell proliferation grown in the different membranes after 7 days of culture. In conclusion, the addition of Sr to materials improved their biocompatibility for bone-derived cells.