My advisor, Prof. Sakai, wanted to come up with a polymer hydrogel that formed fast in the disadvantageous gelation conditions of low polymer concentration. Yet the prepolymers that he could use had an insufficient degree of reactivity at low concentration. To resolve this challenge, we came up with an original idea. We divided the typical gelation process into two steps. In the first step, hyper-branched polymeric clusters are formed by intentionally stopping the gelation reaction prior to the gelation point. Through this process, we can control the distance from the gelation point. In the second step, instead of the prepolymer, we used the polymeric clusters formed by the first process (Figure). This split of the gelation process into two steps makes it possible to shorten the gelation time regardless of the reactivity of the prepolymers.
In clinical practice, injectable hydrogels are needed, and these have to gel in an appropriately short time. Another important requirement is for the hydrogel’s swelling pressure to be appropriately low. This is because swelling in vivo induces compression in surrounding tissues and potentially the failure of the implanted material, which can then cause serious adverse reactions. One of the effective ways to suppress the swelling pressure is to prepare a hydrogel at a low concentration. However, the gelation time is unacceptably high at low polymer concentrations. We needed to accelerate the gelation time under this challenging condition. On the basis of our experiments, our two-step gelation process enabled us to form gels at a low concentration in a short time and with swelling pressure lower than the elastic modulus of soft tissue.
Professors Hoshi and Okamoto, who are ophthalmologists at Tsukuba University, became interested in our work after we discussed it at a conference, and this led to a collaboration about using the hydrogels as artificial vitreous bodies. I was really surprised and pleased when our hydrogel avoided retinal detachment in rabbit eyes. I hope that this hydrogel improves current surgery for retinal detachment, and increases the quality of life of patients.
Our system is based on a simple principle: tuning the gelation time by controlling the distance from the gelation point. This principle is versatile, and thus applicable to other gelation systems. Low swelling pressure and fast-formation in hydrogels were thought to imply a trade-off. I hope that our methodology breaks this trade-off, and opens up the synthesis of new hydrogel systems for biomedical applications.
Our paper: Hayashi, K. et al. Fast-forming hydrogel with ultralow polymeric content as an artificial vitreous body. Nat. Biomed. Eng. 1, 0044 (2017).