Bioinspired Nanospheres as Anti-inflammation and Antisenescence Interfacial Biolubricant for Treating Temporomandibular Joint Osteoarthritis

Abstract

The development of temporomandibular joint (TMJ) osteoarthritis is highly associated with mechanical overloading, which can result in accelerated cartilage degradation and damage due to increased interfacial friction and the release of inflammatory factors and catabolic enzymes. In the present study, we for the first time developed self-assembled drug-free nanospheres with pharmaceutical-active functions, which could be used as an intra-articularly injected biolubricant for the treatment of TMJ osteoarthritis based on a synergistic therapy of enhanced lubrication, anti-inflammation, and antisenescence. The nanospheres possessed the hydrophobic core of dopamine methacrylamide and the hydrophilic shell of sulfobetaine methacrylate, which formed into spherical aggregates in aqueous solution by specific interactions following reversible addition–fragmentation chain transfer polymerization. The biodegradation test, tribological test, and free radical scavenging test showed that the nanospheres were endowed with physiological stability, lubrication enhancement, and free radical scavenging capability. In addition, the in vitro cell test revealed that the nanospheres alleviated inflammatory and senescent phenotype for inflammation and oxidative stress stimulated chondrocytes. Furthermore, the in vivo animal test indicated that the nanospheres, after intra-articular injection into TMJ with an osteoarthritis environment, effectively protected condylar cartilage and subchondral bone from structural damage and attenuated cartilage matrix degradation and aging. In summary, the self-assembled nanospheres might be used as a promising biolubricant for achieving anti-inflammatory and antisenescent treatment of TMJ osteoarthritis.

A cyclic brush zwitterionic polymer based pH-responsive nanocarrier-mediated dual drug delivery system with lubrication maintenance for osteoarthritis treatment

“…2b, compared with water with a coefficient of friction (COF) value of 0.08, the COF values of different concentrations of CB and BB significantly reduced to ∼0.04 at 0.5 Hz, 1 N. The significantly improved lubricating performance is attributed to the zwitterionic charges (–N + (CH 3 ) 2 – and –SO 3 − ) of PSBMA brush side chains, which attracted a large number of water molecules through ionic coupling, forming a stable hydrated lubricating layer. 45,46 It should be noted that there is no significant difference between the COF values of 1 mg mL −1 and 0.25 mg mL −1 . Therefore, we selected the concentration of CB and BB at 0.25 mg mL −1 for subsequent cell and animal experiments.…”

“…) of PSBMA brush side chains, which attracted a large number of water molecules through ionic coupling, forming a stable hydrated lubricating layer. 45,46 It should be noted that there is no significant difference between the COF values of 1 mg mL À1 and 0.25 mg mL À1 . Therefore, we selected the concentration of CB and BB at 0.25 mg mL À1 for subsequent cell and animal experiments.…”

Intra-articular treatment of temporomandibular joint osteoarthritis by injecting actively-loaded meloxicam liposomes with dual-functions of anti-inflammation and lubrication

“…The lubrication dysfunction of articular cartilage is one of the primary reasons for the development of TMJ osteoarthritis, and the increased joint friction can significantly accelerate progression of osteoarthritis [ 62 , 63 ]. It has been reported that phospholipids generate excellent hydration lubrication effect, which is attributed to the hydration layers formed surrounding the positive and negative headgroups [ 64 , 65 ].…”

Recent advances of mussel-inspired materials in osteoarthritis therapy

“…Polyphenols are recognized as natural antioxidants because their abundant reducing phenolic hydroxyl groups transfer electrons to free radicals, thereby protecting cells from excessive free-radical erosion [86]. Zhao et al [87] designed self-assembled nanospheres (PDS) by polymerizing dopamine methacrylamide (DMA) and sulfobetaine methacrylate (SBMA) via reversible addition-fragmentation chain transfer (RAFT) reactions. The excellent radical scavenging ability of the nanospheres is caused by the catechol groups in DMA being able to donate electrons to 2-diphenyl-1picrylhydrazyl (DPPH)• and 2,2′-azino-bis (3ethylbenzothiazoline-6-sulfonic acid) (ABTS) + • to quench the oxidative radicals (figure 11(A)).…”

“…− species in phosphatidylcholine lipids can orient a large number of free water molecules around these charges through the charge-dipole interactions to form a hydration layer [87,94]. At present, various biomimetic zwitterionic polymers, including poly (2methacryloyloxyethyl phosphocholine) (PMPC) [89,95], poly(methacrylic acid 3-sulfopropyl ester potassium salt) (PSPMA) [94], and poly(sulfomethacrylic acid betaine) (PSBMA) [87,96], have been reported to reduce the interfacial friction of the articular cartilage. However, these zwitterionic polymers face problems such as insufficient bulk density, unstable binding with cartilage tissues, and high surface roughness, which affect their lubrication performance in cartilage tissue [97].…”