Bioactivity of Calcium Phosphate Nanoparticles in Scaffolds for Bone Tissue Engineering

Bone fractures and defects pose a significant health challenge, stemming from various sources such as osteoporosis, physical injuries, bone malformations, skeletal disorders, and tumor excisions. These conditions lead to considerable morbidity and a decline in life quality, thereby presenting a substantial public health concern [1]. Bone grafts, despite their widespread use, are plagued by limitations such as scarce availability, potential for infection, and a high rejection rate when integrated with host tissues [2]. An emerging solution is the use of scaffolds that replicate the natural bone structure, which comprises hydroxyapatite nanocrystals of calcium phosphate embedded within collagen nanofibers [3].<br/><br/>In this regard, we suggest a unique scaffold composed of electrospun Poly(lactic-co-glycolic acid) (PLGA) fibers infused with calcium phosphate (CaP) nanoparticles. These nanoparticles are produced using flame spray pyrolysis [4], which provides precise control over the particles' size, composition, and crystallinity. This novel approach enables us to explore the chemical, mechanical, and topographical cues offered by the nanostructures of calcium phosphates. Specifically, we can examine their influence on cellular adhesion, proliferation, and osteogenic differentiation, which are vital processes in bone regeneration and healing.<br/><br/>CaP is known to exist in polymorphic crystal phases (for instance, monocalcium phosphate monohydrate and anhydrous, dicalcium phosphate dihydrate, α- and β-tricalcium phosphate (TCP), amorphous CaP, and hydroxyapatite) and various structures (such as particles, spheres, rods, needles, wires, disks, platelets) [5]. In this study, we employ flame spray pyrolysis to fabricate four different CaP nanoparticles of varying crystallinity, ranging from amorphous to hydroxyapatite. These particles are then incorporated into electrospun PLGA fibers. Viability studies on these scaffolds with pre-osteoblastic cells have demonstrated that cell proliferation increases with the crystallinity of the particles, while significant cellular adhesion was observed regardless of the crystallinity. Furthermore, osteogenic differentiation was studied using the markers alkaline phosphatase and collagen, where the differentiation was observed to be highest for the hydroxyapatite form of calcium phosphate. Interestingly, the manufacturing process also allows the particles to have various ratios of carbonate and phosphate. However, there was no significant influence of the carbonate content on osteogenesis or cell proliferation.<br/><br/>In conclusion, we have conducted a thorough analysis to understand the influence of CaP nanoparticles embedded within scaffolds on osteogenesis. This research could potentially lead to advancements in the field of bone tissue engineering, resulting in more effective treatments for bone fractures and defects.<br/><br/><b>References</b><br/>[1] Wu, A. M. et al. <i>The Lancet Healthy Longevity </i>2, 580-592 (2021).<br/>[2] Flierl MA et al<i>. </i><i>J Orthop Surg Res</i>, 8-33 (2013).<br/>[3] Dorozhkin SV <i>Acta Biomater</i> 6, 715–734 (2010).<br/>[4] GA Sotiriou, SE Pratsinis <i>Environmental Science & Technology</i> 44, 5649-5654 (2010).<br/>[5] Qu, Huawei et al<i>. RSC advances</i> 9, 26252-26262 (2019).