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Objectives: The aim of the present study was to characterize the cellular reaction to a xenogeneic resorbable collagen membrane of porcine origin using a subcutaneous implantation model in Wistar rats over 30 days.
Materials and methods: Ex vivo, liquid platelet-rich fibrin (PRF), a leukocyte and platelet-rich cell suspension, was used to evaluate the blood cell membrane interaction. The material was implanted subcutaneously in rats. Sham-operated rats without biomaterial displayed physiological wound healing (control group). Histological, immunohistological, and histomorphometric analyses were focused on the inflammatory pattern, vascularization rate, and degradation pattern.
Results: The membrane induced a large number of mononuclear cells over the observation period, including lymphocytes, macrophages, and fibroblasts. After 15 days, multinucleated giant cells (MNGCs) were observed on the biomaterial surface. Their number increased significantly, and they proceeded to the center of the biomaterial on day 30. These cells highly expressed CD-68, calcitonin receptor, and MMP-9, but not TRAP or integrin-ß3. Thus, the membrane lost its integrity and underwent disintegration as a consequence of the induction of MNGCs. The significant increase in MNGC number correlated with a high rate of vascularization, which was significantly higher than the control group. Physiological wound healing in the control group did not induce any MNGCs at any time point. Ex vivo blood cells from liquid-PRF did not penetrate the membrane.
Conclusion: The present study suggests a potential role for MNGCs in biomaterial degradation and questions whether it is beneficial to accept them in clinically approved biomaterials or focus on biomaterials that induce only mononuclear cells. Thus, further studies are necessary to identify the function of biomaterial-induced MNGCs.
Clinical relevance: Understanding the cellular reaction to biomaterials is essential to assess their suitability for specific clinical indications and outline the potential benefit of specific group of biomaterials in the respective clinical indications.
Biomaterials are widely used in guided bone regeneration (GBR) and guided tissue regeneration (GTR). After application, there is an interaction between the host immune system and the implanted biomaterial, leading to a biomaterial-specific cellular reaction. The present review focuses on cellular reactions to numerous biomaterials in vivo with consideration of different implantation models and microenvironments in different species, such as subcutaneous implantation in mice and rats, a muscle model in goats and a femur model in rabbits. Additionally, cellular reactions to different biomaterials in various clinical indications within the oro-maxillofacial surgical field were considered. Two types of cellular reactions were observed. There was a physiological reaction with the induction of only mononuclear cells and a pathological reaction with the induction of multinucleated giant cells (MNGCs). Attention was directed to the frequently observed MNGCs and consequences of their appearance within the implantation region. MNGCs have different subtypes. Therefore, the present review addresses the different morphological phenotypes observed within the biomaterial implantation bed and discusses the critical role of MNGCs, their subtypes and their precursors as well as comparing the characteristics and differences between biomaterial-related MNGCs and osteoclasts. Polymeric biomaterials that only induced mononuclear cells underwent integration and maintained their integrity, while polymeric biomaterials that induced MNGCs underwent disintegration with material breakdown and loss of integrity. Hence, there is a question regarding whether our attention should be directed to alternative biological concepts, in combination with biomaterials that induce a physiological mononuclear cellular reaction to optimize biomaterial-based tissue regeneration.