Exercise-induced piezoelectric stimulation for cartilage regeneration in rabbits

Abstract

A biodegradable piezoelectric scaffold excited by exercise promotes chondrogenesis and cartilage regeneration in rabbit osteochondral defects.

Exciting scaffolds regenerate cartilage

Osteoarthritis is a common condition, but curative therapies are limited. Here, Liu and colleagues developed a biodegradable scaffold using PLLA [poly( l -lactic acid)] nanofibers that when placed under applied force generated a piezoelectric charge, leading to improved chondrogenesis in vitro. Rabbits with osteochondral defects in the medial femoral condyle that were treated with the PLLA scaffold demonstrated improved cartilage regeneration and subchondral bone regeneration after 1 or 2 months of exercise to generate piezoelectric charge from the joint loads. Although further work is needed to optimize the scaffold microstructure and components, this study provides evidence that biodegradable piezoelectric scaffolds can use joint-loading exercise to treat osteoarthritis.

Abstract

More than 32.5 million American adults suffer from osteoarthritis, and current treatments including pain medicines and anti-inflammatory drugs only alleviate symptoms but do not cure the disease. Here, we have demonstrated that a biodegradable piezoelectric poly( l -lactic acid) (PLLA) nanofiber scaffold under applied force or joint load could act as a battery-less electrical stimulator to promote chondrogenesis and cartilage regeneration. The PLLA scaffold under applied force or joint load generated a controllable piezoelectric charge, which promoted extracellular protein adsorption, facilitated cell migration or recruitment, induced endogenous TGF-β via calcium signaling pathway, and improved chondrogenesis and cartilage regeneration both in vitro and in vivo. Rabbits with critical-sized osteochondral defects receiving the piezoelectric scaffold and exercise treatment experienced hyaline-cartilage regeneration and completely healed cartilage with abundant chondrocytes and type II collagen after 1 to 2 months of exercise (2 to 3 months after surgery including 1 month of recovery before exercise), whereas rabbits treated with nonpiezoelectric scaffold and exercise treatment had unfilled defect and limited healing. The approach of combining biodegradable piezoelectric tissue scaffolds with controlled mechanical activation (via physical exercise) may therefore be useful for the treatment of osteoarthritis and is potentially applicable to regenerating other injured tissues.