A study of degradation controlling of the oligo-Tetra-PEG hydrogels applied for an artificial vitreous body.

Abstract

Purpose : Development of novel biomaterials for implantation into the eyes is one of the important issues in vitreous surgery. Our team is developing the biocompatible and biodegradable oligo-Tetra-PEG hydrogels as an artificial vitreous body. The oligo-Tetra-PEG gel is formed rapidly via “critical-gel cluster”, has extremely low swelling pressure because of its ultralow polymeric content, and dissociates naturally after a certain period of time. In order to control the degradation period in eyes, we investigated the effect of the ratio of degradable cluster in the hydrogel on the degradation under in vitro accelerated condition.

Methods : Three types of 4arms-PEG reagents, which have respectively thiol (abbreviated to SH), maleimide (MA), and acrylate (ACR) at the terminal of their arms, were used for preparing non-degradable MA_ex-SH and hydrolyzable SH_ex-ACR clusters. 2 mL of 6 g/L hydrogel prepared from mixture of MA_ex-SH and SH_ex-ACR at the ratio of 1-R: R (R means the degradable SH_ex-ACR rate) was immerged in pH 10 phosphate buffer and a relation expression between R value and its degradation period was calculated by regression analysis. Moreover, the acceleration rate was calculated by compared with those immerged in DPBS, 35 °C.

Results : We tuned the ratio of degradable and non-degradable oligo-Tetra PEGs, and observed the longer gelation time (R=0.50, <88sec; R=0.58, 178 sec), and the lower equilibrium storage modulus (R=0.50, 18.6 Pa; R=0.58, 7.7 Pa) as increase of R value. Moreover, the mixture of clusters did not gelled above R=0.75, which was the critical point of gelation. The aqueous solution at pH 10 was selected so that only the ester bond was cleavage. At pH 10 buffer, the degradation rate was 50 times higher than that in DPBS. Based on the results, we estimated the equation predicting the dissociation period from R under accelerated condition. According to the equation and the acceleration rate, we found that the dissociation time of 90 days in DPBS, which is enough period for retinopexy, is achieved at R = 0.618.

Conclusions : We estimated the equation predicting the dissociation period from R under in vitro accelerated condition, which showed the dissociation time of 90 days in DPBS at R = 0.618. The period is considered to be enough for retinopexy.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.