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Impact of tetrahydrocannabinol (THC) on cutaneous wound healing, both alone and in the presence of various sources of stem cells: A swine model
Miller H1, Zilberman B1, De Leo N1, Badach J1, Lin A1, Williamson J1, Behling KC3,4, Behling EM3, Ostrovsky O2, Gaughan J2, Brown S2, Bonawitz S1
1Department of Surgery, Cooper University Hospital, Camden NJ, 2Cooper Research Institute, Cooper University Hospital, Camden NJ, 3Department of Pathology, Cooper University Hospital, Camden, NJ, 4Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ

Background: The primary goal of our study was to determine whether THC use has an impact on cutaneous wound healing in a large animal model, both alone and in the presence of two stem cell lines. We also sought to determine whether two sources of stem cells, adipose derived (ADSCs) and bone marrow derived (BMDSCs), isolated from the same animal, enhance wound healing in both the presence or absence of THC, and if so, which is superior.
Methods: Two Yorkshire swine were obtained, one serving as the control and the other treated with THC. Both animals underwent a wounding procedure consisting of twelve 5cm full thickness dorsal wounds, some of which were injected with either ADSCs or BMDSCs. The treatment animal received a daily oral dose of THC for seven days prior to wounding surgery, and seven days after. Plasma samples were collected during the treatment period to confirm the presence and concentration levels of THC. Post-operative photos were taken every three days and were analyzed to determine wound closure rates. Both animals were sacrificed on post-operative day (POD) 21, and wound biopsies were obtained. Tissue sections from these biopsies were stained with hematoxylin and eosin and submitted for histologic analysis.
Results: Digital analysis of post-operative wound photos demonstrated decreased average wound closure at POD 21 in the untreated wounds of the THC pig, compared to the untreated wounds of the control pig (p < .03). The presence of stem cells did not alter wound closure rates. There were no statistically significant differences in acute inflammatory scores between the two pigs, or between any of the three treatment arms (no stem cells, ADSCs, BMDSCs). Lower rates of chronic inflammation were found in the outer portion of the untreated wounds in the THC pig, compared to the untreated wounds of the control pig (p = .016).
Conclusions: As THC and CBD-containing products become legalized in more states, and their use increases, it is of utmost importance to accurately describe the effects these compounds have on post-operative healing, both in combination and alone. The presence of serum THC appears to delay wound healing and decrease chronic inflammation levels in our large animal model. Further research is needed to confirm these results and define the effect of CBD, as well as how CBD and THC may interact in combination to affect wound healing.


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