In Vitro Macrophage Immunomodulation by Poly(ε-caprolactone) Based-Coated AZ31 Mg Alloy

Abstract

Due to its excellent bone-like mechanical properties and non-toxicity, magnesium (Mg) and its alloys have attracted great interest as biomaterials for orthopaedic applications. However, their fast degradation rate in physiological environments leads to an acute inflammatory response, restricting their use as biodegradable metallic implants. Endowing Mg-based biomaterials with immunomodulatory properties can help trigger a desired immune response capable of supporting a favorable healing process. In this study, electrospun poly(ε-caprolactone) (PCL) fibers loaded with coumarin (CM) and/or zinc oxide nanoparticles (ZnO) were used to coat the commercial AZ31 Mg alloy as single and combined formulas, and their effects on the macrophage inflammatory response and osteoclastogenic process were investigated by indirect contact studies. Likewise, the capacity of the analyzed samples to generate reactive oxygen species (ROS) has been investigated. The data obtained by attenuated total reflection Fourier-transform infrared (FTIR-ATR) and X-ray photoelectron spectroscopy (XPS) analyses indicate that AZ31 alloy was perfectly coated with the PCL fibers loaded with CM and ZnO, which had an important influence on tuning the release of the active ingredient. Furthermore, in terms of degradation in phosphate-buffered saline (PBS) solution, the PCL-ZnO- and secondary PCL-CM-ZnO-coated samples exhibited the best corrosion behaviour. The in vitro results showed the PCL-CM-ZnO and, to a lower extent, PCL-ZnO coated sample exhibited the best behaviour in terms of inflammatory response and receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated differentiation of RAW 264.7 macrophages into osteoclasts. Altogether, the results obtained suggest that the coating of Mg alloys with fibrous PCL containing CM and/or ZnO can constitute a feasible strategy for biomedical applications.

Corrosion Behavior in Magnesium-Based Alloys for Biomedical Applications

“…For instance, Fe 3 O 4 –HA–chitosan coatings can be prepared by electrophoretic deposition, which displays a superior antimicrobial efficacy than HA coating since Fe 2+ can induce the generation of H 2 O 2 , damaging the DNA and proteins in bacteria [ 288 ]. Moreover, electrospun PCL fibers loaded with coumarin and ZnO on the AZ31 Mg alloy perform a positive inflammatory response and an exerted effect on the macrophage–osteoclast differentiation process [ 289 ]. Recently, the etidronate and 3-aminopropyl trimethoxysilane was successfully explored, where the etidronate was known as bisphosphonates applied in the treatment of bone loss and osteoporotic fractures [ 290 ].…”

Macrophage-like Cells Are Responsive to Titania Nanotube Intertube Spacing—An In Vitro Study

“…To assess the degree of macrophage spreading and cell morphology the actin cytoskeleton was fluorescently labeled, as previously reported [ 111 ]. In summary, after 24 h and 72 h in culture, the RAW 264.7 cells were fixed with a cold solution of 4% paraformaldehyde (PFA), permeabilized, and blocked with a solution containing 2% bovine serum albumin (BSA) and 0.1% Triton X-100.…”

The State of the Art and Prospects for Osteoimmunomodulatory Biomaterials

“…Calcium (Ca) involved in the noncanonical Wn5A/Ca2+ signaling pathway and the CaSr signaling cascade [220][221][222][223] Magnesium (Mg) In Vitro ↓ pro-inflammatory cytokine production through the inhibition of the toll-like receptor (TLR) pathway [224] ↓ expression levels of TNF-α and IL-6 ↑ production of TGF-β1 in macrophages [225] In vivo ↓ osteoclastogenic process ↑ osteogenic cell recruitment [226] Silicon (Si) In vivo ↑ local inflammatory response [227] In Vitro contradictory results have been reported, proving the ion's inertness [228] Zinc (Zn) In Vitro ↑ anti-inflammatory cytokine production (IL-10) ↓TNF-αand IL-1β secretion, through TLR-4 pathway modulation [229][230][231][232] ZnO NP: ↑ osteogenic process of osteoblasts [233] ↓ inflammatory activity of RAW264.7 cells ↓differentiation and formation of mature osteoclasts [234] Cobalt (Co) In Vitro: ↑pro-inflammatory effects via the hypoxia-inducible factors (HIFs) [235,236] Strontium (Sr) In Vitro ↓ TNF-α production in human primary monocytes [237,238] ↑ indicates enhancement; ↓ indicates inhibition.…”