The Biomaterial-Induced Cellular Reaction Allows a Novel Classification System Regardless of the Biomaterials Origin

Abstract

Several different biomaterials are being introduced for clinical applications. However, no current material-specific systematic studies define parameters for evaluating these materials. The aim of this retrospective animal study is to classify biomaterials according to the in vivo induced cellular reaction and outline the clinical consequence of the biomaterial-specific cellular reaction for the regeneration process. A retrospective histologic analysis was performed for 13 polymeric biomaterials and 19 bone substitute materials (BSMs) (of various compositions and origins) that were previously implanted in a standardized subcutaneous model. Semiquantitative analyses were performed at days 3, 15, and 30 after implantation according to a standardized score for the induction of multinucleated giant cells (MNGCs) and vascularization rate. The induced cellular reaction in response to different polymeric materials allowed their classification according to the MNGC score in the following groups: class I induced no MNGCs at any time point, class II induced and maintained a constant number of MNGCs over 30 days, and class III induced MNGCs and provided an increasing number over 30 days. All BSMs induced MNGCs to varying extents. Therefore, the resultant BSM classifications are as follows: class I induced MNGCs with a decreasing number, class II induced and maintained constant MNGCs over 30 days, and class III induced MNGCs with increasing number over 30 days. These observations were mostly related to the biomaterial physicochemical properties and were independent of the biomaterial origin. Consequently, the induction of MNGCs and their increase over 30 days resulted in disintegration of the biomaterial. By contrast, the absence of MNGCs resulted in an integration of the biomaterial within the host tissue. This novel classification provides clinicians a tool to assess the capacity and suitability of biomaterials in the intended clinical indication for bone and soft tissue implantations.

Multinucleated Giant Cells Induced by a Silk Fibroin Construct Express Proinflammatory Agents: An Immunohistological Study

“…Different studies have pointed out the importance of biomaterial-specific physicochemical characteristics essential for inducing the inflammatory response [ 12 , 13 ]. Based on these facts, a recent study suggested a new classification of biomaterials according to the induced cellular reactions and the formation kinetics of MNGCs by analyzing the cellular reactions of up to 29 different materials in a subcutaneous implantation model for 30 days [ 25 ]. The authors suggest three classes.…”

“…The authors suggest three classes. Class I included biomaterials that did not induce any MNGCs at any time point [ 25 ]. Class II represented biomaterials that induce an initial number of MNGCs and maintain a sustained number over 30 days, while class III included biomaterials that induce a continuously increasing number of MNGCs over 30 days.…”

“…Interestingly, the pathophysiology and role of biomaterial-induced MNGCs in the degradation process of biomaterials a are still unexplored. Notably, in vivo studies have shown that the number of induced MNGCs is primarily related to biomaterial-specific physicochemical properties [ 25 ]. For example, changes in the size and morphology of beta tricalcium phosphate granules led to significant changes in the number of induced MNGCs in vivo [ 26 , 27 ].…”

Characterization of the Cellular Reaction to a Collagen-Based Matrix: An In Vivo Histological and Histomorphometrical Analysis

“…Based on the induction of MNGCs by different biomaterials, our group recently proposed the classification of these biomaterials into three distinct groups [39]. Class I represents those biomaterials that does not induce MNGCs throughout the implantation period (e.g.…”

Tissue response to biphasic calcium phosphate covalently modified with either heparin or hyaluronic acid in a mouse subcutaneous implantation model

“…Multinucleated giant cells (MNGCs) appear as a reaction to implanted biomaterials 41‐43 . The number of these cells and their persistence greatly influence the further inflammation course of the tissue and healing outcome and are greatly dependent on the physico‐chemical properties of implanted biomaterials 41,42,44 . These cells are also very important in regeneration and healing process since they are involved in the biodegradation of the biomaterial and are related to expression of both pro‐ and anti‐inflammatory molecules, which represent signals for other cells and events that lead to tissue regeneration 41,42 .…”