Ionic NVP-MMA copolymer hydrogel (NM) usually has a swelling equilibrium within 48 hours. When used as tissue filler, its initial swelling rate is too fast, which will bring greater pain to patients after operation. In this paper, the specific degradable crosslinker N, N'-bis (acryloyl) cysteamine (BAC) was introduced into the copolymer hydrogel network to store part of the swelling potential, and then the swelling kinetics of the hydrogel was fine-tuned by gradually breaking the disulfide bond in BAC. The swelling properties, mechanical properties and histocompatibility of NVP-MMA copolymer hydrogels (NMSS) containing disulfide bonds in vitro and in vivo were systematically evaluated.
In vitro simulation experiments showed that the volumetric swelling of NMSS hydrogels continued to increase within 50 days under the reduction of dithiothreitol. It was confirmed that the swelling kinetics of such hydrogels could be divided into two stages: short-term swelling process controlled by osmotic pressure (within 48 hours) and long-term swelling process controlled by disulfide bond disintegration (dozens of days). The compressive strength of NMSS hydrogels is affected by many factors. The swelling degree of NMSS hydrogels caused by the hydrolysis of side methyl ester group and disulfide bond can lead to the decrease of their compressive properties. With the increase of BAC content, the maximum strain of NMSS hydrogel decreases correspondingly. Under the same amount of BAC, half reduction of conventional crosslinking agent is not conducive to the maintenance of mechanical properties of hydrogels. NMSS hydrogels exhibited good mechanical properties. The compressive strength of samples with equilibrium volume swelling of 6-12 ranged from 0.25 MPa to 0.75 MPa.
In vivo implantation experiments showed that compared with the swelling equilibrium of NMSS hydrogels after 1-2 weeks implantation, the time of reaching the swelling equilibrium of NMSS hydrogels was significantly prolonged. The swelling equilibrium of each component hydrogels was usually achieved after more than 4 weeks implantation, which indicated that the initial swelling rate of copolymer hydrogels could be effectively delayed by adding BAC. The results showed that the swelling rate of hydrogels was more slowed down by high BAC content. As the hydrogel network segment rearranged near the sulfhydryl group, the two sulfur bond was formed after the rearrangement of the hydrogel network. The thiol content was the highest when implanted at 1W, then decreased with the implantation time, and almost disappeared at 4W. As the volume swelling of NMSS hydrogel increased limited during implantation, the compressive strength of the hydrogel did not show a significant decreasing trend with the extension of implantation time. The compressive strength of the hydrogel ranged from 0.15 to 0.5 MPa, while the modulus of elasticity was less than 1 MPa. After 2 weeks of implantation, the fibrous capsule began to form. With the prolongation of implantation time, the inflammatory cell reaction around the material gradually weakened. At 16 weeks, it was completely encapsulated by thin and dense fibrous capsule, which indicated that NMSS hydrogel had good histocompatibility.