Ανοσοϊστοχημική, απεικονιστική και εμβιομηχανική μελέτη βιολογικών φαινομένων σε πειραματικό μοντέλο διαταραχών πωρώσεως

Abstract

Background: Fracture healing is a complex, well-orchestrated regenerative process, initiated in response to injury, resulting in optimal skeletal repair and restoration of skeletal function. Despite the progress accomplished towards the treatment of fractures in recent years, impaired healing in terms of delayed union and nonunion are still one of the most severe local complications, as they require a lengthy treatment. Most importantly, they represent a chronic clinical condition, which is difficult for patients to endure. Despite the effectiveness of treatments applied so far, no method has proven its efficacy regarding its reproducibility and cost justification. In this context, the field of Bone Tissue Engineering emerges as a promising alternative, accumulating and implementing knowledge from various disciplines and aiming at bone regeneration by use of biomimetic materials, growth factors and mesenchymal cells.Objective: The aim of this study was to investigate the efficacy of the implementation of biomimetic, naturally-derived and synthetic scaffolds alone or in combination with autologous growth factors and bone marrow stromal cells in terms of their ability to heal critical-size defects.Materials and Methods: Forty-eight NWZ rabbits weighing 2.9 to 3.5 kg were used for the purposes of the present study. An ulna osteotomy (15mm) was performed and the void was filled with naturally-derived and synthetic scaffolds alone or in combination with PRP and BMSCs. Imaging assessment of the regenerative process was made by use of x-rays at 4 and 8 weeks, as well as with CT and micro-CT at 8 weeks. After this time, all animals were sacrificed. Subsequently, the test samples were subjected to histological, imaging and biomechanical assessment.Results: All animals survived until the end of the study. No complications were encountered. The implemented scaffolds proved highly biocompatible and exerted a high degree of bone regenerative capacity, especially when they were seeded with growth factors and mesenchymal stem cells. Histological assessment revealed the existence of mature lamellar bone in all groups, with statistically significant superiority of those groups in which PRP and BMSCs were used concomitantly. Based on the 3D-histomorphometry, the synthetic biomimetic scaffold yielded superior results either alone or in combination with PRP and BMSCs.Conclusions: The implementation of biomimetic scaffolds is a safe alternative therapeutic approach in the treatment of nonunions. The seeding of biomimetic scaffolds with growth factors and stromal cells enhances their bone regenerative quantitative and the qualitative properties. The synthetic biomimetic scaffold used has proven superior, as compared to the naturally-derived one. This “on-site” strategy is safe, minimally invasive, and could be easily translated into the clinical field.