Pigment epithelium derived factor(PEDF)prevents methyl methacrylate monomer-induced cytotoxicity in H9c2 cells

Acrylic bone cements are currently the most frequently and extensively used materials in orthopedic implant treatment. However, adverse effects have been described of acrylic bone cement on the cardiovascular system. In the present study, we examined the cytotoxicity of bone cement ingredient methyl methacrylate（MMA） to cardiomyocytes and the potential detoxifying effect of pigment epithelium-derived factor（PEDF） in H9c2 cells.We found that high concentration of MM A（〉 120 mmol/L） led to necrotic cell death in H9c2 cells. However, MMA at low concentrations（30-90 mmol/L） caused apoptosis. Pretreatment of PEDF prevented MMA-induced cytotoxicity. In addition, PEDF enhanced total superoxide dismutase activities, and decreased MMA-induced production of malonaldehyde. Furthermore, MMA-induced downregulation of Akt activity was suppressed by PEDF.PEDF also increased the levels of peroxisome proliferator activated receptor gamma（PPARγ）and lysophosphatidic acids（LPA） through PEDF receptor. These results indicated that PEDF inhibited MMA-induced cytotoxicity through attenuating oxidative stress, activating the phosphatidylinositol 3-kinase（PI3K）/Akt pathway and/or PEDF receptorLPA-PPARy pathways in H9c2 cells. PEDF may be explored as a candidate therapeutic agent for alleviating bone cement implantation syndrome during orthopedic surgery.

Oxygen metabolism-balanced engineered hydrogel microspheres promote the regeneration of the nucleus pulposus by inhibiting acid-sensitive complexes

Intervertebral disc degeneration(IVDD)is commonly caused by imbalanced oxygen metabolism-triggered inflammation.Overcoming the shortcomings of antioxidants in IVDD treatment,including instability and the lack of targeting,remains challenging.Microfluidic and surface modification technologies were combined to graft chitosan nanoparticles encapsulated with strong reductive black phosphorus quantum dots(BPQDs)onto GelMA microspheres via amide bonds to construct oxygen metabolism-balanced engineered hydrogel microspheres(GM@CS-BP),which attenuate extracellular acidosis in nucleus pulposus(NP),block the inflammatory cascade,reduce matrix metalloproteinase expression(MMP),and remodel the extracellular matrix(ECM)in intervertebral discs(IVDs).The GM@CS-BP microspheres reduce H_(2)O_(2) intensity by 229%.Chemical grafting and electrostatic attraction increase the encapsulation rate of BPQDs by 167%and maintain stable release for 21 days,demonstrating the antioxidant properties and sustained modulation of the BPQDs.After the GM@CS-BP treatment,western blotting revealed decreased acid-sensitive ion channel-3 and inflammatory factors.Histological staining in an 8-week IVDD model confirmed the regeneration of NP.GM@CS-BP microspheres therefore maintain a balance between ECM synthesis and degradation by regulating the positive feedback between imbalanced oxygen metabolism in IVDs and inflammation.This study provides an in-depth interpretation of the mechanisms underlying the antioxidation of BPQDs and a new approach for IVDD treatment.