Ultrasound stimulation of piezoelectric nanocomposite hydrogels boosts cartilage regeneration

Abstract

Osteoarthritis implies a progressive degeneration of the whole joint. Cartilage is particularly affected, with inflammation playing a pivotal role1. In recent years, cartilage regeneration has been pursued through several bioengineering strategies and using different stem cell types2-6. Adipose -derived mesenchymal stromal cells (ASCs) constitute an intriguing and minimally invasive option. However, the use of ASCs for cartilage regeneration is hampered by a relatively inefficient expression of key chondrogenic markers7. Thus, new strategies to boost both in situ targeting and chondrogenesis of ASCs are highly desirable. Here we show that ASCs embedded in a nanocomposite hydrogel including piezoelectric nanomaterials and graphene oxide nanoflakes, and stimulated with ultrasound waves with precisely controlled parameters (1 MHz and 250 mW/cm2, for 5 min once every two days for a period of 10 days) dramatically boost cell chondrogenic commitment. Furthermore, this stimulation regimen also has a considerable anti-inflammatory effect. The proposed nanocomposite hydrogel also shows excellent biocompatibility in vivo. Our results show for the first time the chondrogenic potential of the combined piezoelectric nanoparticle-ultrasound stimulus; the proposed paradigm has the potential to trigger cartilage regeneration in osteoarthritis, focal cartilage defects and other pathological conditions involving cartilage lesions and degeneration. Future efforts should expand preclinical data, and target clinical applications of this therapeutic strategy.

Nanocomposite Bioprinting for Tissue Engineering Applications

“…Inducing the sustained chondrogenic expression of MSCs post printing and hypothetically upon clinical application remains a challenge. One way the differentiation of MSCs has been attempted to be more precisely directed was with the formulation of a nanocomposite hydrogel containing piezoelectric barium titanate nanoparticles and graphene oxide nanoflakes [157]. These materials were investigated as they could be stimulated with controlled ultrasound waves at a variety of frequencies and intensities to direct the chondrogenic differentiation of ASCs.…”

Ultrasound Stimulation of Piezoelectric Nanocomposite Hydrogels Boosts Chondrogenic Differentiation in Vitro, in Both a Normal and Inflammatory Milieu

“…Thus, overall, the synergic use of piezoelectric nanomaterials (alone or embedded in polymeric matrices) and US stimulation for promoting cartilage regeneration has been only argued and proposed as a speculative hypothesis, , but no studies focused on its experimental validation. Even less explored is dose-controlled LIPUS for this purpose.…”

Positioning regulation of organelle network via Chinese microneedle

“…For example, electrical energy-the physical agent most commonly used to activate chondrocyte activities-effectively increases cell proliferation and stimulates the synthesis of molecules related to the extracellular matrix of articular cartilage, such as collagen type II, proteoglycans, and glycosaminoglycans (GAGs) (19). On the basis of the positive effects of electrical energy on chondrocytes, researchers have developed several biological materials with piezoelectric properties for implementing electrical stimulation therapy for chondrocytes in the joint cavity (20,21). As a highly promising means of organelle regulation that complements the advantages of biomaterials, electrical energy is expected to achieve the regulation of the organelle network through the seamless integration of these two processes.…”