Immunocompatible Elastomer with increased resistance to the foreign body response
Polymeric elastomers are extensively employed to fabricate implants intended for prolonged implantation. However, implantation of the elastomers can induce strong immune rejection reaction known as foreign body response (FBR), resulting in the rejection of foreign implants and thereby diminishing their in vivo efficacy. Herein, we present a group of immunocompatible elastomers, termed easy-to-synthesize vinyl-based anti-FBR dense elastomers (EVADE), synthesized via a straightforward and scalable method. In contrast to the pronounced immune reaction triggered by the commonly used implantable elastomers, EVADE materials effectively suppress the inflammation and long-term capsule formation in subcutaneous models of rodents and non-human primates for at least one year and two months, respectively. Implantation of EVADE materials significantly reduces the expression of inflammation-related proteins S100A8/A9 in adjacent tissues compared to polydimethylsiloxane (PDMS). We also show that inhibition or knockout of S100A8/A9 leads to substantial attenuation of fibrosis in mice, suggesting a target for fibrosis inhibition. Continuous subcutaneous insulin infusion (CSII) catheters constructed from EVADE elastomers demonstrate significantly improved longevity and performance compared to commercial catheters. The EVADE materials reported here may enhance and extend function in various medical devices by resisting local immune responses to implanted biomaterials. Overall design: For procedures in mice, the EVADE materials (H50, H70, and H90) and PDMS sheets were cut into discs with a biophysical punch (4 mm in diameter). Elastomers samples were sterilized with 75% ethanol, washed with normal saline, and implanted subcutaneously in C57BL/6 female mice. The implantation procedure was as follows. In brief, mice were anesthetized with 3% isoflurane in oxygen, shaved, and disinfected the skin with iodine. An 8 mm longitudinal incision was made on the dorsal surface using surgical scissors to access the subcutaneous space. Then subcutaneous pockets about 0.5 cm away from the incision were created with blunt forceps to implant the elastomer discs. After implantation, the incisions were closed using 5-0 taper-tipped PGA absorbable sutures. Mice were monitored until recovery from anesthesia and raised for 1 day, 2 weeks, 4 weeks, 3 months, 6 months, or longer, respectively. The mice grew normally without discomfort after the implantation, and no body weight loss was observed during the entire experiment.