Nanoengineered Mechanically Robust Bioactive Particles Disseminated in Chitosan/Collagen Matrix for Osteoporotic Bone Treatment
Kulwinder Kaur1,, Ciara Murphy1,2,
1Tissue Engineering Research Group, Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
2Advanced Materials and BioEngineering Research (AMBER) Centre, Dublin, Ireland
Introduction: Osteoporosis, characterised by depleted bone mass and disrupted bone architecture due to impaired bone remodelling, is the most prevalent metabolic bone disease in the world, causing fractures worldwide at a rate of one every 3 seconds, exceeding health care costs of € 37 billion each year1. Osteoporotic vertebral fractures (OVFs) are the most common complication of osteoporosis and patients determined to have OVFs are 5 times more likely to suffer secondary vertebral fragility fractures2. The clinical gold standard of care for OVFs is vertebroplasty and kyphoplasty, whereby cement is injected into the damaged vertebrae to stabilise the fracture site and reduce pain. These cements are not biodegradable and often leading to complications such as cement leakage and appearance of secondary fractures in adjacent diseased vertebrae1. So, the main aim of this study was to tackle a devastating clinical orthopaedic challenge for which there is currently no reparative treatment specifically OVFs, by developing an advanced mechanically robust biomaterial technology to repair & restore structural integrity and function of disease damaged bone. These materials can be loaded with different agents to promote a targeted delivery, reducing the occurrence of side effects common in conventional treatments.
Methodology: Strontium loaded nano hydroxyl apatite particles (nHAS) functionalized with SWCNTs were prepared by using wet-precipitation method. Thermoresponsive nHAS decorated hydrogels were prepared by using β-GP3 and scaffolds were prepared by freeze dried method4. Physicochemical properties was assessed by using XRD, FTIR, SEM, TGA, DSC,TEM techniques ,degradation profile in PBS and mechanical properties by Zwick Roell testing machine using 5N load. Rat mesenchymal stem cells were seeded on the scaffolds to assess osteogenesis activity via cytotoxicity, proliferation and quantitative RT-PCR to detect key osteogenic markers, ALP activity and calcium deposition. RAW 267.4 cells were used to check the osteoclastogenesis effect of releasing Sr ion via TRAP activity and RT-PCR to detect key osteoclastogenic markers.
Results: Mechanically robust scaffolds for controlled degradation and ion releasing profile were prepared. All the scaffolds was found to be have high water retention ability, porous and bioactive in nature. Scaffolds are found to be non-toxic with enhanced osteogenic differentiation and promote mineralised matrix deposition with increasing content of Sr, and decreased TRAP activity for RAW 264.7. This shows the repair & restore structural integrity of our scaffolds for disease damaged bone without the need of added additional therapeutics.
Conclusion: We developed a therapeutic mechanically robust biomaterial technology that will for the first time, combine mechanically robust carbon nanotubes with antiosteoclastic-ion substituted nano-particles, to target impaired bone remodelling and drive regeneration in a disease compromised load-bearing environment.
Svedbom et al., Arch Osteoporos, 2013
2 Sözen et al., Eur J Rheumatol,2017
Kaur et al., Mater Sci & Eng C, 2021
Murphy et al., Biomater, 2010