Objective Implantoplasty is sometimes performed to eliminate the contaminated titanium surface of peri-implantitis affected implants. Bone regeneration treatments are performed in conjuction with implantoplasty. The aim of this study was to evaluate if produced titanium debris alter the bone-regeneration potential and if dexamethasone-doped polymeric nanoparticles, combined with calcium phosphate, may help to overcome this situation. Methods Four critical bone defects were performed on six New Zealand-bred rabbit skulls. In each of the four bone defects, the following biomaterials were placed: 1) unfilled (control), 2) calcium phosphate granules (CaP), 3) titanium debris (Tid) and CaP, 4) dexamethasone-doped polymeric nanoparticles (DexNPs) doped onto CaP and Tid. After six weeks, animals were euthanized and the bone architecture was evaluated radiographically with micro computed tomography through BoneJ pluging and ImageJ script, and histologically after Von Kossa staining. Results Bone defects filled with CaP plus Tid showed lower defect closure than those filled with CaP. The presence of DexNPs restored the defect closure values, being similar to those of the CaP group. Bone filling area and bone area fraction attained the highest values in the presence of DexNPs. Aligned new bone islands were formed and grew up around the CaP granules, infiltrating its porous structure. In the CaP+Tid group a lower bone ingrowth was formed. When applying DexNPs, bone bridging processes were located surrounding the CaP biomaterial. Significance The presence of Tid reduces the bone healing and DexNPs doped on CaP produced an increase in the osteogenic potential, improving the bone defect closure.