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PLGA microsphere/PVA hydrogel coatings suppress the foreign body reaction for 6 months.

ABSTRACT: The application of dexamethasone releasing poly (lactic-co-glycolic acid) (PLGA) microspheres embedded in a poly vinyl alcohol (PVA) hydrogel coatings have been successfully used in the suppression of the foreign body response (FBR) to implantable glucose sensors. In the current study, dexamethasone-loaded PLGA microspheres were prepared by blending two types of PLGA polymers (RG503H and DLG7E with MW of ca. 25 kDa and 113 kDa, respectively) to achieve long-term (6 months) inhibition of the FBR. The microsphere composition was optimized according to the in vitro drug release profiles. Microspheres with DLG7E/RG503H/dexamethasone = 70/13.3/16.7 wt% composition, when embedded in a PVA hydrogel, provided a continuous drug release for 6 months. By combining the aforementioned microspheres with microspheres composed solely of the DLG7E polymer within a similar PVA hydrogel realized an even longer (>7 months) in vitro drug release. A heat map was constructed to depict the daily in vitro drug released and elucidate possible lag phases that could affect the pharmacodynamic response. These drug-loaded implant coatings were investigated in vivo (rat model) and showed inhibition of the foreign body response for 6 months. These results suggest that the minimum effective daily dose to counter chronic inflammation is ca. 0.1 μg per mg of coating surrounding a 0.5 × 0.5 × 5 mm silicon implant (dummy sensor). Accordingly, these drug-eluting composite coatings can ensure long-term inflammation control for miniaturized implantable devices.

SUBMITTER: Gu B

PROVIDER: S-EPMC8184021 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Invasive intraneural electrodes can control advanced neural-interfaced prostheses in human amputees. Nevertheless, in chronic implants, the progressive formation of a fibrotic capsule can gradually isolate the electrode surface from the surrounding tissue leading to loss of functionality. This is due to a nonspecific inflammatory response called foreign-body reaction (FBR). The commonly used poly(ethylene glycol) (PEG)-based low-fouling coatings of implantable devices can be easily encapsulated and are susceptible to oxidative damage in long-term in vivo applications. Recently, sulfobetaine-based zwitterionic hydrogels have emerged as an important class of robust ultra-low fouling biomaterials, holding great potential to mitigate FBR. The aim of this proof-of-principle in vitro work was to assess whether the organic zwitterionic-poly(sulfobetaine methacrylate) [poly(SBMA)]-hydrogel could be a suitable coating for Polyimide (PI)-based intraneural electrodes to reduce FBR. We first synthesized and analyzed the hydrogel through a mechanical characterization (i.e., Young's modulus). Then, we demonstrated reduced adhesion and activation of fibrogenic and pro-inflammatory cells (i.e., human myofibroblasts and macrophages) on the hydrogel compared with PEG-coated and polystyrene surfaces using cell viability assays, confocal fluorescence microscopy and high-content analysis of oxidative stress production. Interestingly, we successfully coated PI surfaces with a thin film of the hydrogel through covalent bond and demonstrated its high hydrophilicity via water contact angle measurement. Importantly, we showed the long-term release of an anti-fibrotic drug (i.e., Everolimus) from the hydrogel. Because of the low stiffness, biocompatibility, high hydration and ultra-low fouling characteristics, our zwitterionic hydrogel could be envisioned as long-term diffusion-based delivery system for slow and controlled anti-inflammatory and anti-fibrotic drug release in vivo.

Project description:Electrospun materials have been widely explored for biomedical applications because of their advantageous characteristics, i.e., tridimensional nanofibrous structure with high surface-to-volume ratio, high porosity, and pore interconnectivity. Furthermore, considering the similarities between the nanofiber networks and the extracellular matrix (ECM), as well as the accepted role of changes in ECM for hernia repair, electrospun polymer fiber assemblies have emerged as potential materials for incisional hernia repair. In this work, we describe the application of electrospun non-absorbable mats based on poly(ethylene terephthalate) (PET) in the repair of abdominal defects, comparing the performance of these meshes with that of a commercial polypropylene mesh and a multifilament PET mesh. PET and PET/chitosan electrospun meshes revealed good performance during incisional hernia surgery, post-operative period, and no evidence of intestinal adhesion was found. The electrospun meshes were flexible with high suture retention, showing tensile strengths of 3 MPa and breaking strains of 8-33%. Nevertheless, a significant foreign body reaction (FBR) was observed in animals treated with the nanofibrous materials. Animals implanted with PET and PET/chitosan electrospun meshes (fiber diameter of 0.71 ± 0.28 µm and 3.01 ± 0.72 µm, respectively) showed, respectively, foreign body granuloma formation, averaging 4.2-fold and 7.4-fold greater than the control commercial mesh group (Marlex). Many foreign body giant cells (FBGC) involving nanofiber pieces were also found in the PET and PET/chitosan groups (11.9 and 19.3 times more FBGC than control, respectively). In contrast, no important FBR was observed for PET microfibers (fiber diameter = 18.9 ± 0.21 µm). Therefore, we suggest that the reduced dimension and the high surface-to-volume ratio of the electrospun fibers caused the FBR reaction, pointing out the need for further studies to elucidate the mechanisms underlying interactions between cells/tissues and nanofibrous materials in order to gain a better understanding of the implantation risks associated with nanostructured biomaterials.

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PLGA microsphere/PVA hydrogel coatings suppress the foreign body reaction for 6 months.

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Dataset Information

PLGA microsphere/PVA hydrogel coatings suppress the foreign body reaction for 6 months.

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OmicsDI is part of the ELIXIR infrastructure

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PLGA microsphere/PVA hydrogel coatings suppress the foreign body reaction for 6 months.