In vivo evaluation of bone deposition in macroporous titanium implants loaded with mesenchymal stem cells and strontium-enriched hydrogel

Bone-implant integration represents a major requirement to grant implant stability and reduce the risk of implant loosening. This study investigates the effect of progenitor cells and strontium-enriched hydrogel on the osseointegration of titanium implants. To mimic implant-bone interaction, an ectopic model was developed grafting Trabecular Titanium™ (TT) implants into decellularized bone seeded with human bone marrow mesenchymal stem cells (hBMSCs). TT was loaded or not with strontium-enriched amidated carboxymethylcellulose (CMCA) hydrogel and/or hBMSCs. Constructs were implanted subcutaneously in athymic mice and osteodeposition was investigated with microcomputed tomography (micro-CT), scanning electron microscopy (SEM), and pull-out test at 4, 8, and 12 weeks. Fluorescence imaging was performed at 8 and 12 weeks, histology at 4 and 8 weeks. Micro-CT demonstrated the homogeneity of the engineered bone in all groups, supporting the reproducibility of the ectopic model. Fluorescence imaging, histology, SEM and pull-out mechanical testing showed superior tissue ingrowth in TT implants loaded with both strontium-enriched CMCA and hBMSCs. In our model, the synergic action of the bioactive hydrogel and hBMSCs increased both the bone deposition and TT integration. Thus, we suggest that using orthopedic prosthetic implant preloaded with strontium-enriched CMCA and seeded with BMSCs could represent a valid single-step surgical strategy to improve implant osseointegration.