RF-EOI-24-008

Large bone losses associated with aging, cancer, and trauma present significant challenges in clinical orthopaedics and dentistry. These types of bone losses cannot heal through the normal tissue repair process. While commonly used graft materials like ceramics may temporarily fill these gaps, they do not fully restore the bone’s structure and function. Recently, we have developed a new synthetic material that can rapidly generate a large amount of new bone in 14-28 days. Once the new bone has formed, the material completely breaks down and integrates seamlessly with the host bone. This project will evaluate the effectiveness of our innovative biomaterial in treating large bone defects. We will use an animal model to represent elderly human bones to gain regulatory approval. Once approved, our material promises better outcomes for the estimated 110,000+ people in the UK who require bone grafts each year in orthopaedic and dental surgery.

The aim of the proposed research is to conduct a key in vivo test of the rapid bone regeneration capacity via guided periosteal ossification of a novel biomimetic hydroxyapatite/aragonite (HAA, US Patent No. 12,011,515, granted on June 18, 2024) bone graft material. Using aged rats with 5 mm segmental/circular critical-sized bone defects—one of the most challenging bone healing models—we will evaluate the speed, volume, strength, and structure of bone regeneration, as well as enhanced angiogenesis/innervation and complete biodegradation of HAA, compared to existing clinical bone grafts. The results will support obtaining FDA 510K and MHRA approval.

All test materials should meet the ISO 13486 standard with physical-chemical identification. For in vivo tests, 120 rats will be divided into two groups of 60 rats each. Test one uses 5 mm femoral segment bone defects; test two uses 5 mm calvarium circular bone defects. Both tests are grouped as blank, HAA, HAA+TGFbeta/BMP2, and a positive control (Pro Osteon® or Bio-Oss). Samples will be harvested on day 1, then at 2, 4, 12, and 24 weeks for microCT, histology, ultrastructure, mechanical strength, biomarkers of osteogenesis, angiogenesis, and innervation, as well as biodegradation of HAA for statistical comparison.

While bone grafting is a well-established procedure, regenerating large bone defects, especially in the elderly, presents a significant challenge. By translating our novel biomimetic bone graft material into clinical settings, we aim to improve outcomes for the estimated 110,000+ people in the UK who receive bone grafts annually in orthopaedic and dental surgery (over 2 million worldwide). We anticipate that those requiring treatment for extensive lesions will benefit from quicker, better healing, and improved biomechanical properties, without any residual material after complete biodegradation. This will also reduce NHS costs associated with healing complications and supply a $3 billion global market.