Resveratrol Delivery from Porous Poly(lactide-co-glycolide) Scaffolds Promotes an Anti-Inflammatory Environment within Visceral Adipose Tissue

Abstract

As biomaterial therapies emerge to address adipose tissue dysfunction that underlies metabolic disease, the immune response to these systems must be established. As a potential therapy, we are investigating resveratrol delivery from porous poly(lactide-co-glycolide) scaffolds designed to integrate with adipose tissue. Resveratrol was selected for its ability to protect mice and primates from high fat diet and broad anti-inflammatory properties. Herein, we report fabrication of scaffolds with high resveratrol loading that are stable and active for up to one year. In vitro release profiles indicate that drug release is biphasic with a burst release over 3 days followed by a plateau. Surprisingly, we find that PLG scaffold implanted into adipose tissue of mice promotes an anti-inflammatory environment characterized by high arginase-1 and low TNF-α and IL-6 compared to naïve unmanipulated fat. Resveratrol delivery from the scaffold augments this antiinflammatory environment by decreasing monocyte and lymphocyte numbers at the implant site and increasing expression of IL-10 and IL-13, cytokines that promote healthy adipose tissue. In terms of therapeutic applications, implant of scaffolds designed to release resveratrol into the visceral fat decreases MCP-1 expression in mice fed a high fat diet, a molecule that drives both local and systemic inflammation during obesity. Taken together, resveratrol delivery to adipose tissue using poly(lactide-co-glycolide) scaffolds is a promising therapeutic strategy for the treatment of adipose tissue inflammation that drives metabolic disease.

Resveratrol reduces store-operated Ca2+ entry and enhances the apoptosis of fibroblast-like synoviocytes in adjuvant arthritis rats model via targeting ORAI1–STIM1 complex

“…This is because resveratrol is a natural anti-inflammatory and anti-oxidant polyphenol and it has been proven to have the function of relieving abnormal blood picture of AA in the early stage [2]. Its effect of treating chronic anemia was reported to be related to inhibition of IL-1, IL-6 and TNF-α, which was consistent with our results [30, 31]. However, what is the mechanism under the action of resveratrol on blood cells, whether it can affect the proliferation, apoptosis, differentiation and signal transduction of immune cells needed to be confirmed.…”

Modulation of adipocyte size and fat pad weight via resveratrol releasing scaffolds implanted into the epididymal adipose tissue

“…Scaffolds were fabricated from PLG microparticles using a gas foaming, particulate leaching technique. Particles containing resveratrol (Sigma) were fabricated as previously described 38 . Briefly, a 1:3 volume ratio of dichloromethane (Sigma) and ethanol (Sigma) containing 6% wt/wt PLG (75:25 mol ratio lactide to glycolide 0.76 dl/g, Evonik) and 10 mg/ml resveratrol was added to an aqueous solution of 1% wt/vol PVA (Sigma) in a 1:7 volume ratio and homogenized.…”

Cartilage tissue engineering for obesity-induced osteoarthritis: Physiology, challenges, and future prospects

“…A porous poly (lactide-co-glycolide) scaffold was loaded with anti-inflammatory drug resveratrol to decrease activated monocyte and lymphocyte numbers and increase anti-inflammatory expression cytokines in dysfunctional adipose tissue. It was shown that poly(lactide-co-glycolide) scaffold designed to integrate with adipose tissue could reduce the inflammatory tissue response at the implant site, adjunctive resveratrol administration augmented this anti-inflammatory environment, suggesting an important role of biomaterial in immunomodulation [ 162 ]. The anti-inflammatory drug resveratrol also exerts a protective effect on obesity-induced OA by inhibiting TLR4 via the activation of PI3K/Akt signalling pathways in animal models [ 163 ].…”