Investigating the Foreign Body Response and Regenerative Mechanisms in Medical-Grade Polycaprolactone Scaffold Guided Breast Reconstruction in a Porcine Model

To enhance the clinical use of scaffold-guided breast reconstruction (SGBR), the porcine model provides a reliable means of assessing scaffold biocompatibility and tissue regeneration. Understanding the immunological processes triggered by the implantation of medical-grade polycaprolactone (mPCL) scaffolds is essential for elucidating the underlying biology and optimizing the regenerative potential of tissue engineering and regenerative medicine (TE&RM) technologies. This observational work aims to characterize these in vivo processes through systematic, comprehensive immunohistochemical (IHC) analysis based on two preclinical large-animal studies. Key emphasis is placed on evaluating the interplay between immune cell-mediated foreign body response (FBR) and the cellular mechanisms required for successful soft-tissue regeneration, remodelling, and scaffold degradation. Findings indicate that the porcine model provides valuable insights into extracellular matrix (ECM) formation, the interactions between immune cells and the implant surface, and their spatial distribution within the scaffold’s porous architecture. This study further reflects the complexity and spectrum of macrophage phenotypes present 12 months after implantation, exhibiting distinct spatial distributions relative to the scaffold surface, consistent with their established roles in inflammation, tissue regeneration, and remodelling. It also emphasizes the importance of both cellular components and ECM deposition that coexists and may interact to create a distinct microenvironment that varies with local scaffold topography, resulting in location-dependent differences in cellular composition and ECM characteristics relevant to tissue reorganization and homeostasis. Furthermore, this research suggests that extensive neoangiogenesis and vascular remodelling throughout the scaffold architecture are essential for maintaining tissue viability and promoting autologous fat tissue regeneration within the scaffold’s large, fully interconnected pores. These factors are critical for understanding in vivo tissue regeneration following mPCL scaffold implantation and for advancing the translation of SGBR into clinical practice.