Osteogenic and anti-inflammatory effect of the multifunctional bionic hydrogel scaffold loaded with aspirin and nano-hydroxyapatite

Abstract

Although tissue engineering offered new approaches to repair bone defects, it remains a great challenge to create a bone-friendly microenvironment and rebuild bone tissue rapidly by a scaffold with a bionic structure. In this study, a multifunctional structurally optimized hydrogel scaffold was designed by integrating polyvinyl alcohol (PVA), gelatin (Gel), and sodium alginate (SA) with aspirin (ASA) and nano-hydroxyapatite (nHAP). The fabrication procedure is through a dual-crosslinking process. The chemical constitution, crystal structure, microstructure, porosity, mechanical strength, swelling and degradation property, and drug-release behavior of the hydrogel scaffold were analyzed. Multi-hydrogen bonds, electrostatic interactions, and strong “egg-shell” structure contributed to the multi-network microstructure, bone tissue-matched properties, and desirable drug-release function of the hydrogel scaffold. The excellent performance in improving cell viability, promoting cell osteogenic differentiation, and regulating the inflammatory microenvironment of the prepared hydrogel scaffold was verified using mouse pre-osteoblasts (MC3T3-E1) cells. And the synergistic osteogenic and anti-inflammatory functions of aspirin and nano-hydroxyapatite were also verified. This study provided valuable insights into the design, fabrication, and biological potential of multifunctional bone tissue engineering materials with the premise of constructing a bone-friendly microenvironment.

Poly(vinyl alcohol)/Laponite/Layered Double Hydroxide/Hydroxyapatite Nanocomposite Hydrogels for Stimulus-Responsive Devices

“…The LDH clay well-dispersed in the aqueous environment was also in the form of nanoscale thin (thickness ∼1 nm) platelets . The representative chemical formula was shown as [Mg 0.75 Al 0.25 (OH) 2 ] 0.25+ (NO 3 – ) 0.25 , which mainly consisted of positively charged platelets and nitrate anions. , The HAP mineral well-dispersed in the aqueous environment was in the form of nanoscale spheres with a diameter of around 20 nm . The corresponding chemical formula was shown as Ca 10 2+ (PO 4 3– ) 6 (OH – ) 2 , which consisted of both positively charged calcium cations and negatively charged phosphate anions on the surface .…”

“…21,22 The HAP mineral well-dispersed in the aqueous environment was in the form of nanoscale spheres with a diameter of around 20 nm. 23 The corresponding chemical formula was shown as Ca 10 2+ (PO 4 3−…”

Aspirin synergizes with mineral particle-coated macroporous scaffolds for bone regeneration through immunomodulation

“…Given that Asp has been previously shown to enhance MSC osteogenesis on 2D tissue culture plates 30 and 3D scaffolds 47 , we then assessed the direct effect of Asp on MSC osteogenesis in our 3D mTCP-μRB scaffold. Immunostaining of mature bone marker OCN showed Asp increased bone formation as early as week 2 in vivo , with the 20 μg Asp group showing the most robust bone formation (Figure 6 A-B).…”

Aspirin-Loaded Anti-Inflammatory ZnO-SiO2 Aerogel Scaffolds for Bone Regeneration

“…Aerogel materials used as implants are prone to produce acidic byproducts during degradation that are toxic to cells and may lead to disturbances in the bone immune microenvironment, causing immune system responses that can lead to inflammation. , Aspirin (ASA) is a nonsteroidal anti-inflammatory drug (NSAID). As an important immunomodulator, appropriate ASA can enhance bone mineral density and bone mechanical strength and promote the transformation of BMSCs into osteoblasts, thereby accelerating bone regeneration. , It has also been shown that injection of ASA at the site of bone defects can reduce the expression of interferon γ (IFN-γ) and tumor necrosis factor-α (TNF-α) . Unfortunately, ASA has a short half-life and high doses are usually applied to satisfy the normal efficacy, while short time and high concentration of ASA will increase the burden of renal metabolism, digestive tract damage, and other adverse reactions .…”

“…28,29 It has also been shown that injection of ASA at the site of bone defects can reduce the expression of interferon γ (IFNγ) and tumor necrosis factor-α (TNF-α). 30 Unfortunately, ASA has a short half-life and high doses are usually applied to satisfy the normal efficacy, while short time and high concentration of ASA will increase the burden of renal metabolism, digestive tract damage, and other adverse reactions. 31 One way to solve these problems is to load the ASA onto an appropriate carrier to optimize its release behavior.…”