Reduced inflammatory responses to poly(lactic-co-glycolic acid) by the incorporation of hydroxybenzyl alcohol releasing polyoxalate

Abstract

Poly(lactic-co-glycolic acid) (PLGA) has been widely used in biomedical and pharmaceutical applications because of its satisfactory biocompatibility and biodegradation profile. However, its applications for tissue engineering scaffolds have been plagued by inflammatory responses that can lead to fibrotic encapsulation. p-Hydroxybenzyl alcohol (HBA) is a phenolic compound in herbal agents that exerts antioxidant and anti-inflammatory activities. In this work, we developed PLGA blend films containing HBA-incorporated peroxalate polymer (HPOX) and investigated the effects of HPOX on the local inflammatory responses to PLGA in vitro and in vivo. The PLGA/HPOX blend films had no adverse effects on cell viability and elicited a significantly lower production of pro-inflammatory mediators such as tumor necrosis factor-α and reactive oxygen species than PLGA films. We also found that PLGA/HPOX blend films implanted into a rat had significantly diminished inflammatory responses. PLGA/HPOX blends appear to be a promising approach for tissue engineering applications due to their excellent biocompatibility and anti-inflammatory effects.

Mediating macrophage immunity with wogonin in mice with vascular inflammation

“…The advantages of using PLGA as a delivery vehicle include co-delivery of different cargo, targeting of specific tissues or cells and controlled release. In a previous study, the inflammatory function of PLGA to the immune system has been reported to be minor (26); several additional studies demonstrated that PLGA microparticles, instead of PLGA nanoparticles, were able to promote the production of inflammatory cytokines such as TNF-α (28,29). However, considering that PLGA is one of several existing materials approved by the FDA for use in humans, and that PLGA at the nanoscale level does not induce notable inflammation in vitro (29), this material was used in the present study to facilitate the delivery of wogonin.…”

“…The production of inflammatory cytokines in the blood vessels may result in cytoskeletal alterations in the endothelial cells, which may eventually disrupt and increase the permeability of vessels (30). At the beginning of inflammation in blood vessels, the inflammatory cells (monocytes, neutrophils, lymphocytes and macrophages) respond by activating a number of different inflammatory pathways and promoting the production of cytokines (5,28,30). Macrophages are one of major resources for producing inflammatory cytokines (30).…”

Reduction of Inflammatory Responses and Enhancement of Extracellular Matrix Formation by Vanillin-Incorporated Poly(Lactic-co-Glycolic Acid) Scaffolds

“…[36][37][38] As shown in Figure 3, the pure PLGA film generated a large amount of ROS and TNF-a due to transitory stimulation of mitochondrial activity and oxidative stress. 30,32 However, the incorporation of vanillin significantly reduced the PLGA-induced oxidative stress and inflammatory responses. The observations suggest that antioxidant vanillin reduces the inflammatory responses of macrophages to PLGA films and may play beneficial roles in tissue engineering scaffolds.…”

“…28,29 A large body of evidence suggests that vanillin exhibits potent antioxidant, anti-inflammatory, antimutagenic, and antifungal properties. 28,30 However, to our best knowledge, there have been no studies to explore the antiinflammatory activity of vanillin in tissue engineering applications. Therefore, this study was aimed at assessing the effects of vanillin on the PLGA-induced inflammatory responses and ECM formation in vivo as well as in vitro.…”

New development of carbonate apatite-chitosan scaffold based on lyophilization technique for bone tissue engineering

“…Additionally, they must be capable of promoting cell adhesion and retaining their functions [10][11][12][13] . To meet these prerequisites, a number of natural and synthetic polymers, such as polyglycolide acid (PGA), poly lactide-glycolide acid (PLGA) and collagen have been developed [16][17][18][19][20][21] . PGA has excellent mechanical properties but its biomedical applications are limited by its low solubility 16,18,19) , and PLGA causes inflammatory responses that induce fibrotic encapsulation 17,18,21) .…”