Drs. Barralet and Makhoul were awarded $722,926 over a five-year period for their study ‘Induction of transplantable angiosomes for segmental bone defect regeneration’. Dr. Vachon-Presseau was awarded $627,300 over a five-year period for his study ‘Determining the role of the mesolimbic dopaminergic system in opioid craving in chronic pain patients’.
Induction of transplantable angiosomes for segmental bone defect regeneration
The bypass procedure in the heart or legs and more preferably placement of a stent to either bypass or reopen arterial blockages saves lives. The bypass consists of harvesting a nonessential vessel and ‘'plumbing' it in around the blockage. Reconstruction can be achieved by harvesting a tissue segment complete with feeding artery, capillary bed and draining vein, (angiosome), and transplanting, again by 'plumbing' the vessels of these tissue flaps to vessels to the region of repair. Attempts to regrow blood vessels or indeed functional vascularised tissue segments to negate the need for graft harvest have been based on the premise that recapitulating normal anatomy will provide a functional analogue. While there have been some impressive demonstrations of potential, the central issue preventing an improvement in options for patients is the inability to regenerate complete vascular systems, (angiosomes). The main focus of prior research has been on arterial regeneration or in getting arteries to sprout new vessels. Attempts to grow new transplantable tissue in the body have focused on using vein grafts that shortcut (anastomose) the arterial and venous systems that sprout new vessels that in turn are used to regenerate skin and bone. We recently challenged the dogma that new growing tissues require an arterial blood supply and instead considered the intact venous system as a potential regenerative source. We found that without being cut or transplanted, native veins could be induced to sprout profusely by placing a biomaterial around them and that unprecedented amounts of new bone could be grown on these new vessels and then transplanted as flaps. This proposal will explore the regenerative potential of blood vessel walls to grow bone and develop mature new angiosomes. The focus will be on developing minimally invasive approaches, reproducibility and acceleration of the process we have demonstrated as well as determine practical limits of the approach
Pain is the primary reason individuals seek healthcare, the leading utilization of health care resources, and the most important source of disability among working adults in both Canada and the United-States. The estimated cost of chronic pain to the Canadian society is $6 billion/year in medical treatments and 37 billions/year in loss of productivity. Unfortunately, nearly half of severe pain patients are unable to control their pain. Opioids are among the most frequently prescribed drugs for the management of chronic pain and Canada has the second highest opioids prescription rate per capita. Evidence indicates that up to 20-30% of pain patients misuse opioids and that roughly 10% of them will develop opioid addiction. These addictive opioid therapies have led to an alarming increase in rates of hospitalizations and overdose deaths in North America. Opioid craving (i.e., the subjective desire to consume opioids) is one of the strongest predictors of opioid misuse and addiction among patients with chronic pain. There are reasons to believe that neurobiological factors may be associated with opioid craving, but this has yet to be systematically tested in this population. Previous studies demonstrated that substance use disorders are associated with a dysregulation of the dopaminergic system that dampens the ability to feel pleasure and reduces the motivation to pursue normal activities, contributing to the craving for the drug. This proposal aims at studying the dopaminergic system in chronic pain patients using opioids, especially the one craving their medications. This research will help identify targets for treatment and prevention of opioid addiction among chronic pain patients.