Injectable Mussel-Inspired highly adhesive hydrogel with exosomes for endogenous cell recruitment and cartilage defect regeneration.

In the early stage of osteoarthritis (OA), cartilage degradation in the surface region leads to superficial cartilage defect. However, enhancing the regeneration of cartilage defect remains a great challenge for existing hydrogel technology because of the weak adhesion to wet tissue. In the present study, an injectable mussel-inspired highly adhesive hydrogel with exosomes was investigated for endogenous cell recruitment and cartilage defect regeneration. The hydrogel with high bonding strength to the wet surface was prepared using a crosslinked network of alginate-dopamine, chondroitin sulfate, and regenerated silk fibroin (AD/CS/RSF). Compared with commercial enbucrilate tissue adhesive, the AD/CS/RSF hydrogel provided a comparative lap shear strength of 120 kPa, with a similar gelation time and a higher capacity for maintaining adhesive strength. The AD/CS/RSF/EXO hydrogel with encapsulated exosomes recruited BMSCs migration and inflation, promoted BMSCs proliferation and differentiation. Most importantly, the AD/CS/RSF/EXO hydrogel accelerated cartilage defect regeneration in situ, and extracellular matrix remodeling after injection in rat patellar grooves. The exosomes released by the hydrogels could recruit BMSCs into the hydrogel and neo-cartilage via the chemokine signaling pathway. Our findings reveal an injectable and adhesive hydrogel for superficial cartilage regeneration, which is a promising approach for minimally treating cartilage defect with arthroscopic assistance.

Autophagy regulates exosome secretion in rat nucleus pulposus cells via the RhoC/ROCK2 pathway.

Our present study investigated whether exosome secretion of nucleus pulposus cells (NPCs) is regulated by autophagy. Different autophagic states of NPCs were induced by rapamycin (Rap), bafilomycin A1 (Baf) and other agents, and it was found that exosomes were secreted in an autophagy-dependent manner. Activation or inhibition of autophagy increased or decreased, respectively, the amount of exosomes that were released into the extracellular space. In addition, in order to confirm that Rap-promoted release of exosomes was mediated by autophagy rather than other pathways, we used autophagy associated gene 5 (ATG5) small-interfering RNA (siRNA) to silence the expression of ATG5 gene, which is indispensable for autophagy. The results showed that siRNA against ATG5 (siATG5) induced an accumulation of intraluminal vesicles (ILVs) in NPCs and a concomitant decrease in the amount of exosomes isolated from supernatant. Ras homolog gene (Rho) and Rho-associated coiled-coil forming protein kinase (ROCK) family molecules are capable of cytoskeletal remodeling and affecting vesicle transport. Therefore, we carried out targeted interventions and evaluated the effects of the RhoC/ROCK2 pathway on the secretion of exosomes within autophagic environment. Knockdown of RhoC and ROCK2 with corresponding siRNA significantly inhibited the secretion of exosomes originating from ILVs in NPCs, even when NPCs were subsequently treated with Rap. Taken together, our findings suggest that autophagy positively regulates expression levels of RhoC and ROCK2, and that the RhoC/ROCK2 pathway exerts a key function on NPCs-derived exosome secretion.

Treatment of fractures of the ulnar coronoid process.

OBJECTIVE: To discuss the classification, management and outcome of fractures of the ulnar coronoid process. METHODS: Retrospective analysis was carried out in 31 patients (19 men and 12 women of average age 29.8 years [range, 18-52 years]) with fractures of the ulnar coronoid process. The fractures were classified into four major groups based on the extent of injury to the ulnar coronoid process, the state of the anterior bundle of the ulnar collateral ligaments (UCL) and elbow stability. A fracture of the coronoid process less than halfway up was defined as type I (eleven cases); of the middle of the coronoid process with injury of the UCL as type II (nine cases); of the base of coronoid process with dislocation of the elbow joint, sometimes with injury of the UCL, as type III (six cases); and severe comminuted fracture of the coronoid process with elbow instability as type IV (five cases). We chose treatment according to the type of injury. RESULTS: Follow-up was 18-72 months (average 28.6 months). All patients achieved fracture union without inflammation, neural injuries or elbow instability. One type III and two type IV patients had traumatic osteoarthritis, and two type III and two type IV developed heterotopic ossification. There was a statistically significant difference between the ranges of movement of the two-side joints in type IV. CONCLUSION: We choose conservative treatment for type I fractures unless the bone fragment affected movement of the elbow joint, in which case we chose operative treatment so that elbow stability was not affected. Type II and type III fractures with elbow instability were reduced by internal fixation and the ligament repaired or reconstructed. In type IV cases, bone reconstruction was necessary to recover elbow stability. Proper post-operative rehabilitation can decrease the occurrence of traumatic osteoarthritis.