| The final equilibrium swelling of ionic N-Vinyl pyrrolidone-methyl methacrylate copolymer (NM) hydrogel was reached within 48 hours, which may result in severe pain when used as tissue expander. In order to reduce initial swelling rate of the NM hydrogel, specifically degradable crosslinker N,N-bis(acryloyl)-cystamine (BAC) was added to store part of the swelling potential, and then release this potential through cleavage of disulfide bonds to thiol group. In vitro and in vivo swelling behaviors, mechanical strength and histocompatibility of the NMSS hydrogel were systematically evaluated.In vitro experimental results indicated that the volume swelling quotient (Q) of the NMSS hydrogel increased continuously for at least 50 days in the presence of reducing agent dithiothreitol. This phenomenon revealed that the swelling kinetics of the NMSS hydrogel is divided into two-phase, the first phase is reached within 48 hours driven by osmotic pressure due to the strong hydrophilic nature of the hydrogel, while the second phase is derived from the cleavage of disulfide bonds and the time scale could be tens of days. Q of the NMSS hydrogels increased with hydrolysis of MMA unit and cleavage of disulfide bonds and led to reduced compressive strength. Excessive BAC amount in the hydrogel caused increased toughness. In the fixed BAC content, halving normal crosslinkers did not guarantee the original compressive strength. The compressive strength was 0.25-0.75 MPa for the Q 6-12 hydrogel samples.In vivo,it took more than 4 weeks for NMSS hydrogels to reach maximum Q, but it was only 1-2 weeks for NM hydrogels as a comparison. The results showed that additional crosslinker BAC was effective to reduce the initial swelling rate of the hydrogel in vivo. The amount of thiol group derived from cleavage of the disulfide bonds was highest in the first week, and then gradually reduced with implantation time, which might result from re-formation of disulfide bonds due to reaction between adjacent thiol groups in the swollen NMSS hydrogel. As the limited Q increase during period of in vivo swelling, the compressive strength of the hydrogel did not show any decreasing tendency with time. The compressive strength of the swollen hydrogel in vivo was 0.15-0.5 MPa. Fibrous capsule began to form within 2 weeks and became thin and dense and the inflammatory reaction around the hydrogel implants gradually declined with implantation time, indicating the NMSS hydrogels had excellent histocompatibility. |