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.

AN APPROACH TOWARDS HOLISM IN SCIENCE AND ENGINEERING

This paper posits the desirability of a shift towards a holistic approach over reductionist approaches in the understanding of complex phenomena encountered in science and engineering. An argument based on set theory is used to analyze three examples that illustrate the shortcomings of the reductionist approach. Using these cases as motivational points, a holistic approach to understand complex phenomena is proposed, whereby the human brain acts as a template to do so. Recognizing the need to maintain the transparency of the analysis provided by reductionism, a promising computational approach is offered by which the brain is used as a template for understanding complex phenomena. Some of the details of implementing this approach are also addressed.