Macroporous Poly-N-Isopropylacrylamide and Cationic Co-Polymer Hydrogels: Long-Term Subcutaneous Implant Biocompatibility.

Biomaterials have been developed with a great potential in tissue engineering. Hydrogels, especially those based on poly-N-isopropylacrylamide (PNIPAM), have innate mechanical and physicochemical similarities with the native extracellular matrix. We have previously reported the in Vitro compatibility of PNIPAM and its copolymers with a varied number of cell lines, displaying good proliferation rates and bioadhesive capacity. However, the in Vivo biocompatibility assessment is necessary to evaluate. In this work, biocompatibility and immunological acceptance of macroporous hydrogels based on PNIPAM and its co-polymer PNIPAM-co-3%APTA (3-acrylamidopropyl chloride)trimethyl-ammonium) were analyzed using a Wistar female rat model. Hydrogels were synthesized by free radical polymerization and an in Vitro assessment was performed in RAW 264.7 murine macrophages. Then, polymers were implanted subcutaneously and 3-months afterward, grafts were retrieved along with blood and organ samples for haematological, blood chemistry and histological analysis. Cytotoxicity and nitric oxide production did not show variability for the hydrogels. No alterations in the healing process and complete blood count were observed as well as in systemic, liver or kidney toxicity. Histological analysis revealed graft´s integration with the surrounding tissue, without evidence of fibrous capsule or immune cell infiltration. Therefore, these hydrogels are promising biocompatible scaffolds to be used as tissue-engineered constructs.