Bone Regeneration in Small and Large Segmental Bone Defect Models after Radiotherapy Using Injectable Polymer-Based Biodegradable Materials Containing Strontium-Doped Hydroxyapatite Particles

• Published in: International journal of molecular sciences Vol. 24; no. 6; p. 5429
• Main Authors: Ehret, Camille, Aid, Rachida, Dos Santos, Bruno Paiva, Rey, Sylvie, Letourneur, Didier, Amédée Vilamitjana, Joëlle, de Mones, Erwan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 12-03-2023; MDPI
• Subjects: Analysis; Animal models; Animals; Biochemistry, Molecular Biology; Biodegradability; Biodegradable materials; Biomedical materials; Bone growth; Bone marrow; bone reconstruction; Bone Regeneration; Bones; Calcium phosphates; Defects; Femur; Growth factors; Histology; Hydroxyapatite; Hydroxyapatites - chemistry; Immunohistochemistry; Implantation; irradiated bone tissue; Irradiation; Life Sciences; Microspheres; Mineralization; Orthopaedic implants; Osteoconduction; Osteogenesis; Particulate composites; Phosphorus; Polymer industry; Polymers; Polysaccharides; Radiation therapy; Radiotherapy; Rats; Regeneration; Regeneration (physiology); Sheep; Skin & tissue grafts; Stem cells; Strontium; Strontium - chemistry; strontium-doped composite polymer; Tissue engineering; Vascularization; France; strontium-doped composite polymer; vascularization; irradiated bone tissue; bone reconstruction
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24065429

The reconstruction of bones following tumor excision and radiotherapy remains a challenge. Our previous study, performed using polysaccharide-based microbeads that contain hydroxyapatite, found that these have osteoconductivity and osteoinductive properties. New formulations of composite microbeads containing HA particles doped with strontium (Sr) at 8 or 50% were developed to improve their biological performance and were evaluated in ectopic sites. In the current research, we characterized the materials by phase-contrast microscopy, laser dynamic scattering particle size-measurements and phosphorus content, before their implantation into two different preclinical bone defect models in rats: the femoral condyle and the segmental bone. Eight weeks after the implantation in the femoral condyle, the histology and immunohistochemistry analyses showed that Sr-doped matrices at both 8% and 50% stimulate bone formation and vascularization. A more complex preclinical model of the irradiation procedure was then developed in rats within a critical-size bone segmental defect. In the non-irradiated sites, no significant differences between the non-doped and Sr-doped microbeads were observed in the bone regeneration. Interestingly, the Sr-doped microbeads at the 8% level of substitution outperformed the vascularization process by increasing new vessel formation in the irradiated sites. These results showed that the inclusion of strontium in the matrix-stimulated vascularization in a critical-size model of bone tissue regeneration after irradiation.