Importance: Fractures of the hip have devastating effects on function and quality of life. Intramedullary nails (IMN) are the dominant implant choice for the treatment of trochanteric fractures of the hip. Higher costs of IMNs and inconclusive benefit in comparison with sliding hip screws (SHSs) convey the need for definitive evidence.Objective: To compare 1-year outcomes of patients with trochanteric fractures treated with the IMN vs an SHS.Design, Setting, and Participants: This randomized clinical trial was conducted at 25 international sites across 12 countries. Participants included ambulatory patients aged 18 years and older with low-energy trochanteric (AO Foundation and Orthopaedic Trauma Association [AO/OTA] type 31-A1 or 31-A2) fractures. Patient recruitment occurred between January 2012 and January 2016, and patients were followed up for 52 weeks (primary end point). Follow-up was completed in January 2017. The analysis was performed in July 2018 and confirmed in January 2022.Interventions: Surgical fixation with a Gamma3 IMN or an SHS.Main Outcomes and Measures: The primary outcome was health-related quality of life (HRQOL), measured by the EuroQol–5 Dimension (EQ5D) at 1-year postsurgery. Secondary outcomes included revision surgical procedure, fracture healing, adverse events, patient mobility (measured by the Parker mobility score), and hip function (measured by the Harris hip score).Results: In this randomized clinical trial, 850 patients were randomized (mean [range] age, 78.5 [18-102] years; 549 [64.6% female) with trochanteric fractures to undergo fixation with either the IMN (n = 423) or an SHS (n = 427). A total of 621 patients completed follow-up at 1 year postsurgery (304 treated with the IMN [71.9%], 317 treated with an SHS [74.2%]). There were no significant differences between groups in EQ5D scores (mean difference, 0.02 points; 95% CI, −0.03 to 0.07 points; P = .42). Furthermore, after adjusting for relevant covariables, there were no between-group differences in EQ5D scores (regression coefficient, 0.00; 95% CI, −0.04 to 0.05; P = .81). There were no between-group differences for any secondary outcomes. There were also no significant interactions for fracture stability (β [SE] , 0.01 [0.05]; P = .82) or previous fracture (β [SE], 0.01 [0.10]; P = .88) and treatment group.Conclusions and Relevance: This randomized clinical trial found that IMNs for the treatment of trochanteric fractures had similar 1-year outcomes compared with SHSs. These results suggest that the SHS is an acceptable lower-cost alternative for trochanteric fractures of the hip.Trial Registration: ClinicalTrials.gov Identifier: NCT01380444
The integrated repair of bone and cartilage boasts advantages for osteochondral restoration such as a long-term repair effect and less deterioration compared to repairing cartilage alone. Constructing multifactorial, spatially oriented scaffolds to stimulate osteochondral regeneration, has immense significance. Herein, targeted drugs, namely kartogenin@polydopamine (KGN@PDA) nanoparticles for cartilage repair and miRNA@calcium phosphate (miRNA@CaP) NPs for bone regeneration, were in situ deposited on a patterned supramolecular-assembled 2-ureido-4 [lH]-pyrimidinone (UPy) modified gelation hydrogel film, facilitated by the dynamic and responsive coordination and complexation of metal ions and their ligands. This hydrogel film can be rolled into a cylindrical plug, mimicking the Haversian canal structure of natural bone. The resultant hydrogel demonstrates stable mechanical properties, a self-healing ability, a high capability for reactive oxygen species capture, and controlled release of KGN and miR-26a. In vitro, KGN@PDA and miRNA@CaP promote chondrogenic and osteogenic differentiation of mesenchymal stem cells via the JNK/RUNX1 and GSK-3β/β-catenin pathways, respectively. In vivo, the osteochondral plug exhibits optimal subchondral bone and cartilage regeneration, evidenced by a significant increase in glycosaminoglycan and collagen accumulation in specific zones, along with the successful integration of neocartilage with subchondral bone. This biomaterial delivery approach represents a significant toward improved osteochondral repair.
11 April 2021 in Journal of Tissue Engineering and Regenerative Medicine
Articular cartilage regeneration remains a major challenge in orthopedics. Noncanonical Wnt5a is a particularly attractive growth factor in this context; Wnt5a inhibits chondrocyte hypertrophy but maintains chondrogenesis. We designed a novel, vertically oriented‐collagen scaffold. The effect of Wnt5a on MSCs and chondrocytes and the therapeutic effects of the Wnt5a/oriented‐collagen scaffold in terms of osteochondral repair and cartilage integration were evaluated. In vitro, the proliferation, migration, and differentiation of MSCs and chondrocytes treated with Wnt5a, and the mechanisms thereof, were assessed. mRNA microarray analysis was performed to compare the expression profiles of MSCs before and after Wnt5a treatment. In vivo, full‐thickness cylindrical osteochondral defects (4 mm in diameter, 3 mm in depth) were created in the patellar grooves of 24 New Zealand white rabbits and implanted with oriented‐collagen scaffolds (n = 8), Wnt5a/oriented‐collagen scaffolds (n = 8), or nothing (n = 8). After 6 and 12 weeks, integration and tissue responses were evaluated. The proliferation, migration, chondrogenic differentiation, and extracellular matrix formation of/by MSCs and chondrocytes improved greatly after treatment with Wnt5a. Western blotting showed that the PI3K/AKT/JNK signaling pathway was activated. Microarray analysis revealed that the Wnt5a group exhibited a significant upregulation of the PI3K pathway. Reactome GSEA pathway interaction analysis revealed that such upregulation was associated with collagen and extracellular matrix formation. In vivo, the Wnt5a/oriented‐collagen scaffold group exhibited optimal interface integration, cartilage regeneration, and collagenous fiber arrangement, accompanied by significantly increased glycosaminoglycan and collagen accumulations in the zones of regeneration and integration, compared to the other groups. Gene expression analysis showed that the levels of mRNAs encoding genes involved in cartilage formation were significantly increased in the Wnt5a/oriented, collagen scaffold group (all P < .05). Wnt5a promoted the proliferation, migration, and chondrogenic differentiation of MSCs and chondrocytes via the activation of the PI3K/AKT/JNK signaling pathway. The Wnt5a/oriented‐collagen constructs enhanced the structure‐specific regeneration of hyaline cartilage in a rabbit model and may be a promising treatment for the repair of human cartilage defects.