A Methodological Approach to Assessing Biocompatibility: 3D Printing and Subcutaneous Implantation in Rats.

To ensure the safety of PVDF in biomedical applications, biocompatibility tests must be performed after each manufacturing process, as these can alter the material's properties, even if it is inherently biocompatible. Thus, this study aimed to evaluate the in vivo biocompatibility of pure PVDF and PVDF enriched with hydroxyapatite (HAp) in the subcutaneous tissue of Wistar rats and to characterize the crystalline structures of the materials. Subcutaneous implants of PVDF and PVDF-HAp were performed in Wistar rats. Tissue response was evaluated histologically using scoring at 7, 15, and 30 days, according to ISO 10993-6:2016. The crystalline structure of PVDF, HAp, and PVDF-HAp was analyzed by X-ray Diffraction (XRD). FTIR analysis was conducted to further investigate the crystalline structure. XRD analysis confirmed the presence of the α and β phases of PVDF and indicated good interaction between PVDF and HAp in the composite. The FTIR results also demonstrate that the β polar phase is predominant in printed samples. Both materials demonstrated biotolerance, as defined by the ISO standard, inducing only a mild inflammatory reaction. Based on the results, it is concluded that PVDF and the composite with HAp were biotolerable. The study demonstrates a biocompatible baseline, representing a mandatory preliminary step for future orthotopic bone evaluation.