The goal of investigation is to examine the histological response to recombinant human bone morphogenetic protein-2 (rhBMP-2)-loaded demineralized dentin matrices (DDMs) of different origins. The evaluation site is chosen between the cover screw and gingiva, as the poor blood supply allows it to simulate a heterotopic condition. We hypothesize that the antigenicity and immunogenicity of the carrier allogenic DDMs are low enough to maintain both the biocompatibility of the scaffold and the activity of the loaded rhBMP-2. Three patients undergoing simultaneous implant placement and receiving a different type of graft were included: allogenic DDM loaded with rhBMP-2(DDM/rhBMP-2), autogenous DDM/rhBMP-2 and autogenous DDM. Histological specimens were retrieved during the secondary surgery after 3–6 months. In histological examination, particles were encapsulated by dense fibrous tissue without any inflammatory cells. The capsule contained an increased number of cell layers in the DDM/rhBMP-2 (allogenic and autogenous) compared to autogenous DDM. Resorption activity was higher in autogenous DDM/rhBMP-2 than in allogenic DDM/rhBMP-2. Within the limitations of this report, results demonstrated the successful use of DDM as a potential rhBMP2 carrier. Further studies will be required to confirm the safety and effectiveness of autogenous and allogenic DDM/rhBMP-2.