Enzymatically cross-linkable phenol-conjugated glycol chitosan was prepared by reacting glycol chitosan with 3-(4-hydroxyphenyl)propionic acid (HPP). The chemical modification was confirmed by FTIR, 1 H-NMR and UV spectroscopy. Glycol chitosan hydrogels (HPP-GC) with or without rhBMP-2 were prepared by the oxidative coupling of the substituted phenol groups in the presence of hydrogen peroxide and horse radish peroxidase. Rheological characterization demonstrated the feasibility of developing hydrogels with varying storage moduli by changing the polymer concentration. The gel presented a microporous structure with pore sizes ranging from 50-350 mm. The good viability of encapsulated 7F2 osteoblasts indicated non-toxicity of the gelation conditions. In vitro release of rhBMP-2 in phosphate buffer solution showed B11% release in 360 h. The ability of the hydrogel to maintain the in vivo bioactivity of rhBMP-2 was evaluated in a bilateral critical size calvarial bone defect model in Col3.6 transgenic fluorescent reporter mice. The presence of fluorescent green osteoblast cells with overlying red alizarin complexone and yellow stain indicating osteoclast TRAP activity confirmed active cell-mediated mineralization and remodelling process at the implantation site. The complete closure of the defect site at 4 and 8 weeks post implantation demonstrated the potent osteoinductivity of the rhBMP-2 containing gel.

Statins are currently used as an effective cholesterol-lowering medication through inhibition of the mevalonate pathway, but recent studies show their potential for bone repair. The bone anabolic effects of statins have been largely attributed to their ability to enhance BMP-2 expression in osteoblast cells. In vitro studies have demonstrated that statins can increase the expression of osteogenic and angiogenic markers such as alkaline phosphatase, vascular endothelial growth factor, and osteocalcin in cells. In vivo, statins have been shown to promote significant new bone growth when injected systemically or locally in combination with a scaffold. The potential anabolic effects of statins on bone make them attractive candidates to support bone regeneration. Since the molecular pathways by which statins induce osteoblast differentiation are still unclear, further investigations are required to elucidate the detailed cellular signaling mechanisms involved to determine the type of statin, optimal dose and mode of delivery to effectively utilize their anabolic effect. This also warrants the development of novel vehicles to locally deliver statins for the desired time periods to support optimal tissue regeneration in vivo.

To avoid unnecessary preclinical testing of Covidien's hemostatic agent patch product, a test platform is needed to test the "time-to-hemostasis" of blood using the patch. The test platform needs to utilize in vitro testing, providing an alternative to in vivo testing. Understanding how "time-to-hemostasis" is affected by Covidien's various products will help surgeons prevent unnecessary bleeding when performing surgery, aid doctors healing large wounds from military events or other accidents, and will be useful in many other ways to prevent bleeding out that could fatally harm the patient.In order to stop the use of animal testing for this product, Covidien would like to have a bench-top in vitro testing device for their products. This device must be able to accurately simulate blood flow through a wound site, as well as simulate the hemostasis process of closing the wound through blood clotting. Important features of the finished device include accurate simulation of blood flow through a wounded tissue, accurately measure the time-to-hemostasis, and the ability to test multiple types of hemostat products efficiently. The device will provide Covidien with an in-house alternative to in vivo testing, saving time and expenditure when testing hemostats. V ACKNOWLEDGEMENTS