Biologic Functionalization of a Biphasic Bone Substitute With Enamel Matrix Derivative Modulates Early Foreign Body Reaction in a Subcutaneous Mouse Model.

Abstract

BACKGROUND/AIM: Biologic enhancement of bone grafts with enamel matrix derivative (EMD) may improve regenerative outcomes by modulating the host tissue response. This study evaluated the in vivo tissue reaction to a biphasic bone substitute (Maxresorb), used alone or in combination with EMD, in a subcutaneous mouse model. MATERIALS AND METHODS: Forty BALB/c mice received subcutaneous implants of Maxresorb, EMD, Maxresorb+ EMD, or underwent sham surgery. Tissue samples were harvested at 15- and 30-days post-implantation. Histological and immunohistochemical analyses were performed to assess inflammation, neovascularization, fibrosis, and the presence of macrophages and biomaterial-associated multinucleated giant cells (BMGCs). Statistical analysis was conducted using ANOVA (≤0.05). RESULTS: The Maxresorb+ EMD group showed higher inflammatory scores, increased numbers of macrophages and BMGCs, and enhanced neovascularization compared with the other groups, particularly at 30 days. Despite this elevated cellular activity, all test conditions were classified as non-irritant or slightly irritant according to ISO 10993-6. CONCLUSION: The combination of EMD and Maxresorbenhanced early tissue responses without adverse effects. These findings support the biocompatibility of this combination and suggest potential regenerative benefits through biologically driven material functionalization.