Exhausted local lactate accumulation via injectable nanozyme-functionalized hydrogel microsphere for inflammation relief and tissue regeneration.

Shen, Jieliang; Chen, Ao; Cai, Zhengwei; Chen, Zhijie; Cao, Ruichao; Liu, Zongchao; Li, Yuling; Hao, Jie · Bioact Mater · 2022

basic_science · Level V

Where this comes from

Abstract

Local lactate accumulation greatly hinders tissue repair and regeneration under ischemic condition. Herein, an injectable microsphere (MS@MCL) for local lactate exhaustion was constructed by grafting manganese dioxide (MnO<sub>2</sub>) -lactate oxidase (LOX) composite nanozyme on microfluidic hyaluronic acid methacrylate (HAMA) microspheres via chemical bonds, achieving a long-term oxygen-promoted lactate exhaustion effect and a long half-life <i>in vivo</i>. The uniform and porous microspheres synthesized by microfluidic technology is beneficial to <i>in situ</i> injection therapy and improving encapsulation efficiency. Furthermore, chemical grafting into HAMA microspheres through amide reactions promoted local enzymatic concentration and activity enhancement. It was showed that the MS@MCL eliminated oxidative and inflammatory stress and promoted extracellular matrix metabolism and cell survival when co-cultured with nucleus pulposus cells (NPCs) <i>in vitro</i>. In the rat degenerative intervertebral disc model caused by lactate injection, MS@MCL showed a long-term therapeutic effect in reducing intervertebral height narrowing and preventing extracellular matrix (ECM) degradation as well as inflammatory damage <i>in vivo</i>. Altogether, this study confirms that this nanozyme-functionalized injectable MS@MCL effectively improves the regenerative and reparative effect in ischemic tissues by disposing of enriched lactate in local microenvironment.