PRECISELY ENGINEERED IN NANOSCALE HYDROXYAPATITE AND ZINC OXIDE FOR ENHANCING 3D-PRINTED SCAFFOLDS AND MEMBRANES FOR BONE REGENERATION APPLICATIONS

Regenerating bone tissue in cases of large gaps remains a significant challenge. Insufficient or slow bone regeneration can lead to considerable patient suffering and is a challenge for orthopedic surgeons. Traditional approaches, where allografts, autografts, and xenografts, are used to fill the gaps often come with undesirable side effects. Synthetic bone grafts, primarily based on calcium phosphate materials, offer a biodegradable alternative but still have limitations. Bone tissue naturally consists of hydroxyapatite platelets and collagen, with hydroxyapatite particles measuring in the nanometer range. Application of synthetic nanoparticles that mimicking this natural structure may enhance bone regeneration, offering advantages over conventional materials. However, achieving consistent, precisely sized biomimetic nanoparticles is critical. We have developed a microwave hydrothermal synthesis (MHS) technology that enables precise control over nanoparticle size through regulated synthesis time. This method allows us to produce nanoparticles ranging from 10 nm to 50 nm, with the smallest sizes (10-15 nm) closely resembling natural hydroxyapatite platelets, as confirmed by X-ray diffraction analysis. Nanoparticles with sizes below 15 demonstrate enhanced bioactivity and solubility. Using these 15 nm nanoparticles, we can create a uniform, approximately 100 nm-thick coating on 3D-printed scaffolds and membranes. These coatings strongly adhere to various materials, including polymers, metals, ceramics, and glass, promoting new bone growth within the scaffolds' pores. Additionally, multi-layer coatings can be developed, incorporating different nanoparticles to introduce antibacterial or angiogenic properties—for instance, a zinc oxide nanoparticles layer for improved vascularization or silver nanoparticles for antibacterial properties. Our nano-hydroxyapatite particles are produced under strict ISO 13485 standards for medical implants and have successfully passed comprehensive biocompatibility tests required according by MDR (Medical Devices Regulation). They are ready for clinical evaluation, whether as part of a nanoparticle-based paste mixed with blood or bone marrow to fill bone defects or as scaffold coatings. These nanoparticles represent a significant advancement in nanomedicine, offering a biomimetic approach to bone regeneration and opening new avenues for research and clinical applications.