Dadsetan, Mahrokh

AbstractIn tissue engineering, development of an osteoconductive construct that integrates with host tissue remains a challenge. In this work, the effect of bone‐like minerals on maturation of pre‐osteoblast cells was investigated using polymer‐mineral scaffolds composed of poly(propylene fumarate)‐co‐poly(caprolactone) (PPF‐co‐PCL) and nano‐sized hydroxyapatite (HA). The HA of varying concentrations was added to an injectable formulation of PPF‐co‐PCL and the change in thermal and mechanical properties of the scaffolds was evaluated. No change in onset of degradation temperature was observed due to the addition of HA, however compressive and tensile moduli of copolymer changed significantly when HA amounts were increased in composite formulation. The change in mechanical properties of copolymer was found to correlate well to HA concentration in the constructs. Electron microscopy revealed mineral nucleation and a change in surface morphology and the presence of calcium and phosphate on surfaces was confirmed using energy dispersive X‐ray analysis. To characterize the effect of mineral on attachment and maturation of pre‐osteoblasts, W20‐17 cells were seeded on HA/copolymer composites. We demonstrated that cells attached more to the surface of HA containing copolymers and their proliferation rate was significantly increased. Thus, these findings suggest that HA/PPF‐co‐PCL composite scaffolds are capable of inducing maturation of pre‐osteoblasts and have the potential for use as scaffold in bone tissue engineering. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 2549–2557, 2015.

Osteosarcoma is a bone tumor that affects children and young adults. 2‐Methoxyestradiol (2‐ME), a naturally occurring estrogen metabolite, kills osteosarcoma cells, but does not affect normal osteoblasts. In order to effectively target osteosarcoma and improve the therapeutic index of the drug 2‐ME, we have encapsulated 2‐ME in a composite of oligo‐(polyethylene glycol) fumarate (OPF) hydrogel and poly (lactic‐co‐glycolic acid) (PLGA) microspheres and investigated the effect of polymer composition on 2‐ME release kinetics and osteosarcoma cell survival. The in vitro study shows that 2‐ME can be released in a controlled manner over 21‐days. The initial burst releases observed on day 1 were 50% and 32% for OPF and OPF/PLGA composites, respectively. The extended release kinetics show that 100% of the encapsulated 2‐ME is released by day 12 from OPF, whereas the OPF/PLGA composites showed a release of 85% on day 21. 2‐ME released from the polymers was biologically active and blocked osteosarcoma cell proliferation in vitro. Also, comparison of 2‐ME delivery in osteosarcoma cells in culture, shows that direct treatment has no effect after 3 days, whereas polymer‐mediated delivery produces anti‐tumor effects that could be sustained for 21 days. These findings show that the OPF and PLGA polymeric system may prove to be useful in controlled and sustained delivery of 2‐ME and could be further explored in the treatment of osteosarcoma. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 2491–2499, 2013.