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Injectable and biodegradable piezoelectric hydrogel for osteoarthritis treatment.

ABSTRACT: Osteoarthritis affects millions of people worldwide but current treatments using analgesics or anti-inflammatory drugs only alleviate symptoms of this disease. Here, we present an injectable, biodegradable piezoelectric hydrogel, made of short electrospun poly-L-lactic acid nanofibers embedded inside a collagen matrix, which can be injected into the joints and self-produce localized electrical cues under ultrasound activation to drive cartilage healing. In vitro, data shows that the piezoelectric hydrogel with ultrasound can enhance cell migration and induce stem cells to secrete TGF-β1, which promotes chondrogenesis. In vivo, the rabbits with osteochondral critical-size defects receiving the ultrasound-activated piezoelectric hydrogel show increased subchondral bone formation, improved hyaline-cartilage structure, and good mechanical properties, close to healthy native cartilage. This piezoelectric hydrogel is not only useful for cartilage healing but also potentially applicable to other tissue regeneration, offering a significant impact on the field of regenerative tissue engineering.

SUBMITTER: Vinikoor T

PROVIDER: S-EPMC10558537 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Injectable and biodegradable piezoelectric hydrogel for osteoarthritis treatment.

Vinikoor Tra T Dzidotor Godwin K GK Le Thinh T TT Liu Yang Y Kan Ho-Man HM Barui Srimanta S Chorsi Meysam T MT Curry Eli J EJ Reinhardt Emily E Wang Hanzhang H Singh Parbeen P Merriman Marc A MA D'Orio Ethan E Park Jinyoung J Xiao Shuyang S Chapman James H JH Lin Feng F Truong Cao-Sang CS Prasadh Somasundaram S Chuba Lisa L Killoh Shaelyn S Lee Seok-Woo SW Wu Qian Q Chidambaram Ramaswamy M RM Lo Kevin W H KWH Laurencin Cato T CT Nguyen Thanh D TD Nguyen Thanh D TD

Nature communications 20231006 1

Osteoarthritis affects millions of people worldwide but current treatments using analgesics or anti-inflammatory drugs only alleviate symptoms of this disease. Here, we present an injectable, biodegradable piezoelectric hydrogel, made of short electrospun poly-L-lactic acid nanofibers embedded inside a collagen matrix, which can be injected into the joints and self-produce localized electrical cues under ultrasound activation to drive cartilage healing. In vitro, data shows that the piezoelectri ...[more]

PMID: 37802985

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Project description:BackgroundOsteoarthritis (OA) is a degenerative joint disease characterized by the progressive degeneration of articular cartilage, leading to pain, stiffness, and loss of joint function. The pathogenesis of OA involves multiple factors, including increased intracellular reactive oxygen species (ROS), enhanced chondrocyte apoptosis, and disturbances in cartilage matrix metabolism. These processes contribute to the breakdown of the extracellular matrix (ECM) and the loss of cartilage integrity, ultimately resulting in joint damage and dysfunction. RNA interference (RNAi) therapy has emerged as a promising approach for the treatment of various diseases, including hATTR and acute hepatic porphyria. By harnessing the natural cellular machinery for gene silencing, RNAi allows for the specific inhibition of target genes involved in disease pathogenesis. In the context of OA, targeting key molecules such as matrix metalloproteinase-13 (MMP13), which plays a critical role in cartilage degradation, holds great therapeutic potential.ResultsIn this study, we developed an innovative therapeutic approach for OA using a combination of liposome-encapsulated siMMP13 and NG-Monomethyl-L-arginine Acetate (L-NMMA) to form an injectable hydrogel. The hydrogel served as a delivery vehicle for the siMMP13, allowing for sustained release and targeted delivery to the affected joint. Experiments conducted on destabilization of the medial meniscus (DMM) model mice demonstrated the therapeutic efficacy of this composite hydrogel. Treatment with the hydrogel significantly inhibited the degradation of cartilage matrix, as evidenced by histological analysis showing preserved cartilage structure and reduced loss of proteoglycans. Moreover, the hydrogel effectively suppressed intracellular ROS accumulation in chondrocytes, indicating its anti-oxidative properties. Furthermore, it attenuated chondrocyte apoptosis, as demonstrated by decreased levels of apoptotic markers.ConclusionIn summary, the injectable hydrogel containing siMMP13, endowed with anti-ROS and anti-apoptotic properties, may represent an effective therapeutic strategy for osteoarthritis in the future.

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Injectable and biodegradable piezoelectric hydrogel for osteoarthritis treatment.

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Injectable and biodegradable piezoelectric hydrogel for osteoarthritis treatment.

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