Thursday, December 26, 2024
12/26/2024
Abstract Reconstruction of large and major bone defects remains a significant challenge in modern medicine. The golden treatment so far has been to use replacement auto or allo-grafts which however struggle with problems of immune rejection, infection, donor-site morbidity and especially, limited tissue supplies. Tissue regenerative engineering approach relying on biomaterials to construct artificial “engineering” bone grafts has therefore become an important field. While many biomaterials are safe, they often require an addition of potentially-toxic growth factors, stem cells, biologics or drugs to promote healing and tissue regeneration. In fact, there has not been any clinical success to heal critical-sized (large) bone defects by using only a safe biomaterial scaffold that is free of seeded stem-cells, exogenous growth-factors, biologics or drugs. Electrical stimulation (ES) has been shown to effectively promote bone healing and could offer a safe natural stimulation as bioelectrical signals are ubiquitous inside the body. Several electrical stimulators are available in the market and used clinically for bone healing. Yet, while external stimulators are not very effective, implanted devices rely on toxic batteries. Several researchers have attempted to pre-induce electrical signal (i.e. surface charge) on the surface of biomaterial scaffolds to promote bone healing and avoid the use of battery-based ES. This method however only creates transient charge that quickly gets neutralized when the scaffold is implanted or directly interfaced with living cells. In this regard, piezoelectric materials, which can always produce surface charge when subjected to external force or vibration, appear to be an excellent choice to create a battery-free and remotely controlled electrical stimulator. Unfortunately, common piezoelectric materials are also non-degradable and/or even toxic, which renders them not favorable for serving as implanted tissue scaffolds. Here, we propose a novel bionic bone composite scaffold (BBCS) which is completely biodegradable and can be remotely activated by ultrasound (US) to electrically stimulate bone regeneration via the combination of piezoelectric self-charging effect and osteo- inductive ions released from the degradation of beta-Tricalcium Phosphate (β-TCP). This will be the first pure biomaterial scaffold without using any exogenous stem cells, growth factors, drugs or any biologics to heal a large bone defect. We design the project with three specific aims; Aim 1 is to assess piezoelectric charge, mechanical/degradation properties and osteogenesis of the piezoelectric BBCS with US activation in vitro. Aim 2 is to assess healing of critical-sized long-bone defects, using the BBCS and US activation in vivo. And Aim 3 is to study the molecular mechanism to understand the engineering rules on how the BBCS can induce and enhance osteogenesis of stem cells.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).