Energy-Supporting Enzyme-Mimic Nanoscaffold Facilitates Tendon Regeneration Based on a Mitochondrial Protection and Microenvironment Remodeling Strategy.
Shikun WangZhixiao YaoXinyu ZhangJuehong LiChen HuangYuanming OuyangYun QianCunyi FanPublished in: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2022)
Tendon injury is a tricky and prevalent motor system disease, leading to compromised daily activity and disability. Insufficient regenerative capability and dysregulation of immune microenvironment are the leading causes of functional loss. First, this work identifies persistent oxidative stress and mitochondrial impairment in the regional tendon tissues postinjury. Therefore, a smart scaffold incorporating the enzyme mimicry nanoparticle-ceria nanozyme (CeNPs) into the nanofiber bundle scaffold (NBS@CeO) with porous, anisotropic, and enhanced mechanical properties is designed to innovatively explore a targeted energy-supporting repair strategy by rescuing mitochondrial function and remodeling the microenvironment favoring endogenous regeneration. The integrated CeNPs scavenge excessive reactive oxygen species (ROS), stabilize the mitochondria membrane potential (ΔΨm), and ATP synthesis of tendon-derived stem cells (TDSCs) under oxidative stress. In a rat Achilles tendon defect model, NBS@CeO reduces oxidative damage and accelerates structural regeneration of collagen fibers, manifesting as recovering mechanical properties and motor function. Furthermore, NBS@CeO mediates the rebalance of endogenous regenerative signaling and dysregulated immune microenvironment by alleviating senescence and apoptosis of TDSCs, downregulating the secretion of senescence-associated secretory phenotype (SASP), and inducing macrophage M2 polarization. This innovative strategy highlights the role of NBS@CeO in tendon repair and thus provides a potential therapeutic approach for promoting tendon regeneration.
Keyphrases
- stem cells
- oxidative stress
- anterior cruciate ligament reconstruction
- dna damage
- reactive oxygen species
- rotator cuff
- tissue engineering
- cell therapy
- cell death
- diabetic rats
- ischemia reperfusion injury
- multiple sclerosis
- induced apoptosis
- bone marrow
- genome wide
- endoplasmic reticulum stress
- climate change
- stress induced
- pi k akt