Chondroprotective effect of zinc oxide nanoparticles in conjunction with hypoxia on bovine cartilage‐matrix synthesis

Abstract

Articular cartilage is a tissue specifically adapted to a specific niche with a low oxygen tension (hypoxia), and the presence of such conditions is a key factor in regulating growth and survival of chondrocytes. Zinc deficiency has been linked to cartilage-related disease, and presence of Zinc is known to provide antibacterial benefits, which makes its inclusion attractive in an in vitro system to reduce infection. Inclusion of 1% zinc oxide nanoparticles (ZnONP) in poly octanediol citrate (POC) polymer cultured in hypoxia has not been well determined. In this study we investigated the effects of ZnONP on chondrocyte proliferation and matrix synthesis cultured under normoxia (21% O2 ) and hypoxia (5% O2 ). We report an upregulation of chondrocyte proliferation and sulfated glycosaminoglycan (S-GAG) in hypoxic culture. Results demonstrate a synergistic effect of oxygen concentration and 1% ZnONP in up-regulation of anabolic gene expression (Type II collagen and aggrecan), and a down regulation of catabolic (MMP-13) gene expression. Furthermore, production of transcription factor hypoxia-inducible factor 1A (HIF-1A) in response to hypoxic condition to regulate chondrocyte survival under hypoxia is not affected by the presence of 1% ZnONP. Presence of 1% ZnONP appears to act to preserve homeostasis of cartilage in its hypoxic environment.

<p>Enhancing ZnO-NP Antibacterial and Osteogenesis Properties in Orthopedic Applications: A Review</p>

“…Moreover, the scaffold with 10 wt% ZnO-NPs promoted osteogenic properties rather than chondrogenic differentiation, which is consistent with the findings of a previous study. 145 Mirza et al 145 studied the chondrogenic effects of 1% ZnO-NPs decorated with poly (octanediol citrate) polymer, and found that they improved chondrocyte viability, upregulated the expression of cartilage matrix-specific genes (COL2A1 and ACAN), and inhibited the expression of the matrix degradation gene (MMP-13).This cartilagepromoting ability could be attributed to Zn 2+ release. Some studies claim that Zn 2+ can enhance chondrocyte proliferation, while also preventing cartilage loss by activating the P13/Akt pathway.…”

“…Moreover, the scaffold with 10 wt% ZnO-NPs promoted osteogenic properties rather than chondrogenic differentiation, which is consistent with the findings of a previous study. 145 …”

Piezoelectric smart biomaterials for bone and cartilage tissue engineering

“…Piezoelectric zinc oxide has not shown any toxic effects in micrometer and larger size ranges [ 101 ], but it has been demonstrated toxicity in nano size due to the production of reactive oxygen species [ 102 ]. Significant results has reported on zinc oxide nanoparticles dispersed in the polymeric scaffold along with hypoxia have shown ability to synthesis cartilage [ 103 ] . According to Material Safe Data Sheet (MSDS) databases LD50 of acute oral ZnO is 7950 mg/kg for mice shows no significant toxicity [ 104 ].…”

Polycaprolactone Triol–Citrate Scaffolds Enriched with Human Platelet Releasates Promote Chondrogenic Phenotype and Cartilage Extracellular Matrix Formation

“…Apart from their elastic mechanical properties for engineering of soft tissues, CA-based polyester materials could be formed into hard composites for orthopedic implants [27]. The solid material phase can be introduced in various filler forms such as ''bioglasses'' or nanoparticles [28,29]. This opportunity was explored previously for production of multi-functional scaffolds that promote chondrocyte proliferation while at the same time deplete the bacteria in their environment by controlled release of zinc oxide (ZnO) nanoparticles from biodegradable polymer matrix [28].…”

“…The solid material phase can be introduced in various filler forms such as ''bioglasses'' or nanoparticles [28,29]. This opportunity was explored previously for production of multi-functional scaffolds that promote chondrocyte proliferation while at the same time deplete the bacteria in their environment by controlled release of zinc oxide (ZnO) nanoparticles from biodegradable polymer matrix [28]. The problem of bacterial biofilm formation upon surgical intervention must be considered when designing a potential material for scaffold fabrication.…”