Intra-articular injection of therapeutics is an effective strategy for treating osteoarthritis (OA), but it is hindered by rapid drug diffusion, thereby necessitating high-frequency injections. Hence, the development of a biofunctional hydrogel for improved delivery is required. In this study, we introduce a liposome-anchored teriparatide (PTH (1–34)) incorporated into a gallic acid-grafted gelatin injectable hydrogel (GLP hydrogel). We show that the GLP hydrogel can form in situ and without affecting knee motion after intra-articular injection in mice. We demonstrate controlled, sustained release of PTH (1–34) from the GLP hydrogel. We find that the GLP hydrogel promotes ATDC5 cell proliferation and protects the IL-1β-induced ATDC5 cells from further OA progression by regulating the PI3K/AKT signaling pathway. Further, we show that intra-articular injection of hydrogels into an OA-induced mouse model promotes glycosaminoglycans synthesis and protects the cartilage from degradation, supporting the potential of this biomaterial for OA treatment.
Osteosarcoma is an aggressive malignant neoplasm, and it is of great significance to the fabrication and investigation of the anti-tumor mechanism of nanomedicine in the treatment of osteosarcoma. Herein, a cinnamaldehyde polymeric prodrug micelle with pH-sensitive charge-conversion ability (mPEG-b-P(C7-co-CA)) was fabricated, and the anti-osteosarcoma mechanism of mPEG-b-P(C7-co-CA) micelle was investigated. mPEG-b-P(C7-co-CA) micelles were prepared by self-assembly method, and their diameter was 227 nm. mPEG-b-P(C7-co-CA) micelles could regulate the cell cycle and inhibit the proliferation of 143B cells, which was demonstrated by flow cytometry analysis, CCK-8 assay and 5-Ethynyl-2′-deoxyuridine (EdU) staining. The wound-healing assay and transwell assay showed that mPEG-b-P(C7-co-CA) micelles effectively inhibited the migration and invasion of 143B cells. It was proven that mPEG-b-P(C7-co-CA) micelles downregulated the levels of proliferation and apoptosis-related proteins and affected osteosarcoma migration and invasion by inhibiting the epithelial-mesenchymal transition (EMT). In addition, mPEG-b-P(C7-co-CA) micelles can also inhibit the transcriptional activity of the PI3K/Akt signaling pathway. Therefore, these findings provide new evidence for the pharmacological effects of mPEG-b-P(C7-co-CA) micelles.
Objectives: This study aims to investigate the possible association and comparison between anterolateral approach (ALA) and posterolateral approach (PLA) and postoperative lower limb discrepancy (LLD) in selective total hip arthroplasty (THA). Patients and methods: April 2021 and July 2021, a total of 266 consecutive patients (126 males, 140 females; mean age: 46.7±13.6 years; range, 22 to 60 years) who underwent unilateral primary THA via the ALA or the PLA were retrospectively analyzed. The operations were performed by a single surgical team. All patients were divided into two groups according to the approach: ALA group (n=66) and PLA group (n=200). Relevant data were recorded. Diagnosis including hip osteoarthritis, developmental dysplasia of the hip (DDH), aseptic avascular necrosis (AVN), and inflammatory arthritis were noted. Perioperative follow-up radiographs were evaluated and measured to compare the postoperative LLD and offset. The association between two approaches and postoperative LLD and offset was analyzed using the univariate and multivariate linear regression analysis. Results: The mean follow-up was 20±3.7 (range, 16 to 25) months. Univariate analysis revealed that the postoperative LLD, the postoperative acetabular offset, and hospital costs were lower in the ALA group than the PLA group (p <0.01). However, the offset and length of stay were comparable between the two groups (p>0.05). Multivariate analysis revealed that the PLA (β=4.71; 95% confidence interval [CI]: 1.78 to 7.64), preoperative LLD (β=0.29; 95% CI: 0.21 to 0.37), DDH (β=5.01; 95% CI: 1.47 to 8.55), and AVN (β=3.81; 95% CI: 0.50 to 7.12) were the main contributors to the postoperative LLD. Conclusion: Our study results suggest that the ALA may be superior to the PLA in controlling the postoperative LLD among some of the selective unilateral primary THA patients. Both the ALA and the PLA were comparable in terms of the restoration of offset.
Background Ankle fracture is common and the treatment is embarrassed. Enhanced Recovery After Surgery (ERAS) has been successfully adopted for the improvement of efficacy and quality. However, application of ERAS in ankle fracture patients especially at the early stage is variable and remains to be clarified. We intent to explore the effect of ERAS among ankle fracture patients. Methods There were 29 male and 51 female patients aged 41.71 ± 14. 51 years who were consecutively grouped into non-ERAS group (n = 40) and ERAS group (n = 40). Univariate analysis and multiple linear regression analysis were applied to assess the association in outcomes and variables. Results AOFAS at post-operative 3 month (PO3M) and post-operative 6 month (PO6M), costs, length of stay (LOS), and pre-operative LOS were verified significantly in univariate analysis. Multiple linear regression analysis revealed that ERAS can improve American Orthopaedic Foot and Ankle Society (AOFAS) at PO3M (β = 7.06, 95% CI, 4.45–9.65) and PO6M (β = 5.08, 95% CI, 2.35–7.80), reduce costs (β = -6885.13, 95% CI, -12089.40 - -1680.85) and LOS (β = -3.27, 95% CI, -4.97 - -1.57) among ankle fracture patients. With the numbers available, no significant differences were observed (p༞0.05) for the AOFAS at post-operative 12 month (PO12M) and post-operative 24 month (PO24M), complications, or opioids consumption. Conclusion We found ERAS is superior to general protocol among proper ankle fracture patients, which can enhance rehabilitation especially at the early stage and improve medical quality and efficiency by reducing costs and LOS. ERAS protocol may have a promising future and worth promoting.
Intra-articular (IA) injection of drugs is an effective strategy in treating osteoarthritis disease. However, the rapid drug loss and high-frequency injections are the main issues. Hence, we verily efforts to design and develop a point of care-based new biofunctional hydrogel by nanoengineer and chemistry approach. In this study, a novel gallic acid-grafted gelatin injectable hydrogel loaded with liposomes-anchored teriparatide (GGA@Lipo@PTH: GLP) was developed with an enzyme-linking method to control PTH release, aimed to alleviate osteoarthritis progress and protect chondrocytes degradation. In vitro studies of the GLP hydrogel promoted ATDC5 proliferation and upregulation of key proteins expression in the PI3K/AKT signaling pathway. Further, in vivo IA injection results of GLP confirmed the controlled release of PTH, promotes the secretion of glycosaminoglycan and protects the cartilage from degradation in DMM mice. Therefore, our study explored that the developed novel GLP hydrogel could be an alternative potential biomaterial in the osteoarthritis treatment.
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