Hydrogels based on poly(ethylene oxide) and poly(tetramethylene oxide) or poly(dimethyl siloxane). III. In vivo biocompatibility and biostability

Abstract

To investigate the effects of polymer chemistry and topology (linear or graft copolymer) on in vivo biocompatibility and biostability based on cage implant system, various hydrogels, composed of short hydrophilic [polyethylene oxide (PEO)] and hydrophobic block, were prepared by polycondensation reaction. Poly(tetramethylene oxide) (PTMO) or poly(dimethyl siloxane) (PDMS) was chosen as a hydrophobic block because of their wide utilization as a biomaterial. By using the specimens retrieved from rats killed after 1, 2, 3, 5, and 7 weeks' implantation, cellular and material responses were assessed. Most hydrogels showed a comparable value of macrophage density to Pellethane(R), control polymer, whereas they did significantly lower foreign body giant cell (FBGC) density and coverage because of the presence of PEO. However, PEO block length and polymer topology did not affect macrophage adhesion and FBGC formation in our polymer composition. The hydrogel based on PDMS alone showed significantly lower macrophage density and FBGC density than Pellethane(R), indicating that PDMS plays a role in inhibiting cellular adhesion. The results obtained from gel permeation chromatography curve and Fourier transform infrared spectra exhibited that all the polymers were susceptible to oxidative degradation in vivo. Although Pellethane(R) revealed surface degradation by 5 weeks in vivo, hydrogels showed rapid degradation in the bulk within 2 weeks because of the penetration of oxidative chemicals released from phagocytic cells into PEO domain of phase-separated hydrogels. The more significant degradation was observed in the hydrogels with longer PEO block and PTMO as a hydrophobic block instead of PDMS. It was evident that the minor degradation could be achieved by grafting PEO and adopting PDMS as a hydrophobic block in the hydrogel.

Chronic inflammatory responses to microgel‐based implant coatings

“…Previous efforts have focused on hydrogel coatings that exhibit in vitro resistance to protein adsorption and leukocyte adhesion to reduce biomaterial‐mediated related inflammation 14, 15, 30–35. Although these coatings reduce biofouling in vitro , some of these materials still exhibit high levels of adherent leukocytes and continued inflammation in vivo with significant fibrous encapsulation of the implant.…”

“…For instance, in vitro protein adsorption was significantly suppressed by photochemically immobilized polymer coatings on silicone rubber substrates and by polyethylene oxide‐like tetraglyme coatings, yet neither treatment significantly reduced fibrous capsule thickness when implanted subcutaneously 14, 34. In contrast, other coatings, such as dihydroxypropyl methacrylate, PEG, and phosphorylcholine‐based polymers, have shown reductions in fibrous encapsulation compared to the base substrates 30–33, 35. The reductions in fibrous capsule thickness elicited by these coatings are comparable to those observed in the present study.…”

Anti-inflammatory Surface Coatings Based on Polyelectrolyte Multilayers of Heparin and Polycationic Nanoparticles of Naproxen-Bearing Polymeric Drugs

“…As an example, when taken up by endocytosis, Hep inhibits the nuclear transcription factor-κB (NF-κB), which in turn suppresses leukocyte activation turning down pro-inflammatory cytokines production. − Moreover, Hep-based coatings have demonstrated superior properties when compared to other GAGs-based systems due to high wettability, negative surface charge, and intrinsic anti-inflammatory activity . Although these surface coatings eventually reduce FBR, there is still lack of definitive solutions. , …”

Reduced acute inflammatory responses to microgel conformal coatings

“…The rationale for these passive approaches is that reduction in protein adsorption will lead to reduced leukocyte adhesion and activation, thereby attenuating the extent of the foreign body reaction. Although many of these coatings exhibit reduced protein adsorption and leukocyte adhesion/activation in vitro , inconsistent results have been obtained regarding the ability of these materials to reduce in vivo acute and chronic inflammatory responses [6, 11, 13, 16]. Possible explanations for the mixed in vivo results with these coatings include insufficient non-fouling behavior, coating degradation, and inflammatory mechanism(s) independent from protein adsorption.…”