As an alternative treatment option for patients with large segmental bone defects, scaffold-guided bone tissue regeneration (SGBTR) is an innovative approach which has reached clinical translation. 3D-printed custom-made biodegradable scaffolds made from medical grade polycaprolactone and tricalcium phosphate (PCL-TCP) provide a pro-regenerative environment for cellular migration, proliferation, and differentiation to eventually regenerate the organ bone. Nevertheless, in order to improve implant design and patient care, thorough immunological and regenerative characterization must be performed using histological and immunohistochemical (IHC) methods in established preclinical animal models.
Over the past two decades, we have developed well-defined comprehensive histological- and IHC protocols to study SGBTR in an ovine tibial large segmental defect model. We here present qualitative histological and IHC data of over 350 ovine surgeries at different timepoints up to three years (1). Through this extensive investigation, we have uncovered a dynamic interplay of converging, yet, compartmentalized processes involved in the formation of woven bone and lamellar bone, as well as the release of anti-inflammatory and pro-regenerative extracellular matrix (ECM) proteins. Our findings show that regenerative and foreign body related immunological processes occur concurrently and should be considered holistically instead of distinctly. By exploring the interplay between biomaterial and biological processes, we can unlock insights into the osteoimmunological processes that govern SGBTE which have the potential to exceed existing limitations and foster a new era of advancement in the field of regenerative medicine and tissue engineering.