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.

Orthopedic bioactive implants: Hydrogel enrichment of macroporous titanium for the delivery of mesenchymal stem cells and strontium.

Insufficient implant stability is an important determinant in the failure of cementless prostheses. To improve osseointegration, we aim at generating a bioactive implant combining a macroporous titanium (TT) with a biocompatible hydrogel to encapsulate osteo-inductive factors and osteoprogenitor cells. Amidation and cross-linking degree of an amidated carboxymethylcellulose hydrogel (CMCA) were characterized by FT-IR spectrometry and mechanical testing. Bone marrow mesenchymal stem cells (BMSCs) from osteoarthritic patients were cultured on CMCA hydrogels, TT, and TT loaded with CMCA (TT + CMCA) with an optimized concentration of SrCl2 to evaluate cell viability and osteo-differentiation. Amidation and cross-linking degree were homogeneous among independent CMCA batches. SrCl2 at 5 µg/mL significantly improved BMSCs osteo-differentiation increasing calcified matrix (P < 0.01), type I collagen expression (P < 0.05) and alkaline phosphatase activity. TT + CMCA samples better retained cells into the TT mesh, significantly improving cell seeding efficiency with respect to TT (P < 0.05). BMSCs on TT + CMCA underwent a more efficient osteo-differentiation with higher alkaline phosphatase (P < 0.05) and calcium levels compared to cells on TT. Based on these in vitro results, we envision the association of TT with strontium-enriched CMCA and BMSCs as a promising strategy to generate bioactive implants promoting bone neoformation at the implant site.