Collagen Type II-Based Injectable Materials for In situ Repair and Regeneration of Articular Cartilage Defect.

Repairing and regenerating articular cartilage defects (ACDs) have long been challenging for physicians and scientists. The rise of injectable materials provides a novel strategy for minimally invasive surgery to repair ACDs. In this study, we successfully developed injectable materials based on collagen type II, achieving hyaline cartilage repair and regeneration of ACDs. Analysis was conducted on the regenerated cartilage after materials injection. The histology staining demonstrated complete healing of the ACDs with the attainment of a hyaline cartilage phenotype. The biochemical and biomechanical properties are similar to the adjacent native cartilage without noticeable adverse effects on the subchondral bone. Further transcriptome analysis found that compared with the Native cartilage adjacent to the defect area, the Regenerated cartilage in the defect area repaired with type II collagen-based injection materials showed changes in cartilage-related pathways, as well as down-regulation of T cell receptor signaling pathways and interleukin-17 signaling pathways, which changed the immune microenvironment of the ACD area. Overall, these findings offer a promising injectable approach to treating ACDs, providing a potential solution to the challenges associated with achieving hyaline cartilage in situ repair and regeneration while minimizing damage to the surrounding cartilage.

A biomimetic targeted nanosystem delivering synergistic inhibitors for glioblastoma immune microenvironment reprogramming and treatment.

Efficient drug delivery across the blood-brain barrier is imperative for treating glioblastoma (GBM). This study utilized the GBM cell membrane to construct a biomimetic targeted nanosystem (GMNPs@AMD/RAPA) that hierarchically releases the CXCR4 antagonist AMD3100 and the mTOR pathway inhibitor rapamycin (RAPA) for reprogramming the tumor immune microenvironment and suppressing the progression of GBM. By initially inhibiting the CXCL12/CXCR4 axis, the tumor microenvironment (TME) was reprogrammed to enhance the infiltration of cytotoxic T lymphocytes (CTLs) into the TME while suppressing tumor cell survival, proliferation, and angiogenesis. Subsequently, through further cellular uptake and degradation of the nanoparticles, the mTOR pathway inhibitor RAPA was released, further suppressing the tumor progression. This study successfully combined chemotherapy and immunotherapy, achieving effective synergistic therapeutic effects, and suppressing the progression of GBM.

Applications of nanotechnology in remodeling the tumour microenvironment for glioblastoma treatment.

With the increasing research and deepening understanding of the glioblastoma (GBM) tumour microenvironment (TME), novel and more effective therapeutic strategies have been proposed. The GBM TME involves intricate interactions between tumour and non-tumour cells, promoting tumour progression. Key therapeutic goals for GBM treatment include improving the immunosuppressive microenvironment, enhancing the cytotoxicity of immune cells against tumours, and inhibiting tumour growth and proliferation. Consequently, remodeling the GBM TME using nanotechnology has emerged as a promising approach. Nanoparticle-based drug delivery enables targeted delivery, thereby improving treatment specificity, facilitating combination therapies, and optimizing drug metabolism. This review provides an overview of the GBM TME and discusses the methods of remodeling the GBM TME using nanotechnology. Specifically, it explores the application of nanotechnology in ameliorating immune cell immunosuppression, inducing immunogenic cell death, stimulating, and recruiting immune cells, regulating tumour metabolism, and modulating the crosstalk between tumours and other cells.

Remote-sensing monitoring of colored dissolved organic matter in the Arctic Ocean.

In the Arctic Ocean, variations in the colored dissolved organic matter (CDOM) have important value and significance. This study proposed and evaluated a novel method by combining the Google Earth Engine with a multilayer back-propagation neural network to retrieve CDOM concentration. This model performed well on the testing data and independent validation data (R2 = 0.76, RMSE = 0.37 m-1, MAPD = 35.43 %), and it was applied to Moderate Resolution Imaging Spectroradiometer (MODIS) images. The CDOM distribution in the Arctic Ocean and its main sea areas was first depicted during the ice-free period from 2002 to 2021, with average CDOM concentration in the range of 0.25 and 0.31 m-1. High CDOM concentration appeared in coastal areas affected by rivers on the Siberian side. The CDOM concentration was highly correlated with salinity (r = -0.92) and discharge (r > 0.68), while melting sea ice diluted seawater and CDOM concentration.

Harnessing Nanomedicine for Cartilage Repair: Design Considerations and Recent Advances in Biomaterials.

Cartilage injuries are escalating worldwide, particularly in aging society. Given its limited self-healing ability, the repair and regeneration of damaged articular cartilage remain formidable challenges. To address this issue, nanomaterials are leveraged to achieve desirable repair outcomes by enhancing mechanical properties, optimizing drug loading and bioavailability, enabling site-specific and targeted delivery, and orchestrating cell activities at the nanoscale. This review presents a comprehensive survey of recent research in nanomedicine for cartilage repair, with a primary focus on biomaterial design considerations and recent advances. The review commences with an introductory overview of the intricate cartilage microenvironment and further delves into key biomaterial design parameters crucial for treating cartilage damage, including microstructure, surface charge, and active targeting. The focal point of this review lies in recent advances in nano drug delivery systems and nanotechnology-enabled 3D matrices for cartilage repair. We discuss the compositions and properties of these nanomaterials and elucidate how these materials impact the regeneration of damaged cartilage. This review underscores the pivotal role of nanotechnology in improving the efficacy of biomaterials utilized for the treatment of cartilage damage.

Rejuvenating Hyaline Cartilaginous Phenotype of Dedifferentiated Chondrocytes in Collagen II Scaffolds: A Mechanism Study Using Chondrocyte Membrane Nanoaggregates as Antagonists.

Joint cartilage lesions affect the global population in the current aging society. Maintenance and rejuvenation of articular cartilage with hyaline phenotype remains a challenge as the underlying mechanism has not been completely understood. Here, we have designed and performed a mechanism study using scaffolds made of type II collagen (Col2) as the 3D cell cultural platforms, on some of which nanoaggregates comprising extracts of chondrocyte membrane (CCM) were coated as the antagonist of Col2. Dedifferentiated chondrocytes were, respectively, seeded into these Col2 based scaffolds with (antCol2S) or without (Col2S) CCM coating. After 6 weeks, in Col2S, the chondrocytes were rejuvenated to regain hyaline phenotype, whereas this redifferentiation effect was attenuated in antCol2S. Transcriptomic and proteomic profiling indicated that the Wnt/ß-catenin signaling pathway, which is an opponent to maintenance of the hyaline cartilaginous phenotype, was inhibited in Col2S, but it was contrarily upregulated in antCol2S due to the antagonism and shielding against Col2 by the CCM coating. Specifically, in antCol2S, since the coated CCM nanoaggregates contain the same components as those present on the surface of the seeded chondrocytes, the corresponding ligand sites on Col2 had been preoccupied and saturated by CCM coating before exposure to the seeded cells. The results indicated that the ligation between Col2 ligands and integrin α5 receptors on the surface of the seeded chondrocytes in antCol2S was antagonized by the CCM coating, which facilitates the Wnt/ß-catenin signaling toward the loss of hyaline cartilaginous phenotype. This finding reveals the contribution of Col2 for maintenance and rejuvenation of the hyaline cartilaginous phenotype in chondrocytes.

Catechin-Functionalized Cationic Lipopolymer Based Multicomponent Nanomicelles for Lung-Targeting Delivery.

Catechins from green tea are one of the most effective natural compounds for cancer chemoprevention and have attracted extensive research. Cancer cell-selective apoptosis-inducing properties of catechins depend on efficient intracellular delivery. However, the low bioavailability limits the application of catechins. Herein, a nano-scaled micellar composite composed of catechin-functionalized cationic lipopolymer and serum albumin is constructed. Cationic liposomes tend to accumulate in the pulmonary microvasculature due to electrostatic effects and are able to deliver the micellar system intracellularly, thus improving the bioavailability of catechins. Albumin in the system acts as a biocompatible anti-plasma absorbent, forming complexes with positively charged lipopolymer under electrostatic interactions, contributing to prolonged in vivo retention. The physicochemical properties of the nano-micellar complexes are characterized, and the antitumor properties of catechin-functionalized materials are confirmed by reactive oxygen species (ROS), caspase-3, and cell apoptosis measurements. The role of each functional module, cationic polymeric liposome, and albumin is revealed by cell penetration, in vivo animal assays, etc. This multicomponent micellar nanocomposite has the potential to become an effective vehicle for the treatment of lung diseases such as pneumonia, lung tumors, sepsis-induced lung injury, etc. This study also demonstrates that it is a great strategy to create a delivery system that is both tissue-targeted and biologically active by combining cationic liposomes with the native bioactive compound catechins.

Application of 3D-printed osteotomy guide plates in proximal femoral osteotomy for DDH in children: a retrospective study.

BACKGROUND: Patients with developmental dysplasia of the hip (DDH) have complex proximal femoral deformities, and orthopedic surgery lacks objectivity. Expectations for surgical outcomes are often not achieved, and postoperative problems are common. Using 3D-printed technology in orthopedics offers a novel approach to precise and individualized treatment in modern orthopedics. The aim of this study was to investigate the value of the application of 3D-printed osteotomy guide plates in femoral osteotomy. The clinical indices of femoral osteotomy in children with DDH using 3D-printed osteotomy guide plates were compared with those of traditional osteotomy. METHODS: The clinical data of children with DDH who underwent open reduction and Salter pelvic osteotomy combined with femoral osteotomy from September 2010 to September 2020 were retrospectively collected and analyzed. Based on the inclusion and exclusion criteria, a total of 36 patients were included in the study: 16 in the guide plate group and 20 in the conventional group. Operation time (total), operation time (femoral side), X-ray fluoroscopy times (total), X-ray fluoroscopy times (femoral side) and intraoperative blood loss were analyzed and compared between the two groups. Comparison of treatment-related indicators such as postoperative neck-shaft angle, postoperative anteversion angle, hospitalization time, and hospitalization expenses is made between the two groups. The two groups of patients were evaluated at the last follow-up using the McKay clinical evaluation criteria. RESULTS: Between the two groups, there were significant differences in operation time (total), operation time (femoral side), X-ray fluoroscopy times (total), X-ray fluoroscopy times (femoral side) and intraoperative blood loss (P < 0.05). The postoperative neck-shaft angle, postoperative anteversion angle, hospitalization time and hospitalization expenses did not differ significantly (P > 0.05). The MacKay clinical evaluation did not significantly differ at the most recent follow-up (P > 0.05). CONCLUSIONS: Children with DDH undergoing proximal femoral osteotomy using 3D-printed osteotomy guide plates benefit from a simpler surgical procedure, shorter operative time, less bleeding and less radiation exposure during surgery. This technique is of great clinical value.

Cartilage Tissue Engineering in Practice: Preclinical Trials, Clinical Applications, and Prospects.

Articular cartilage defects significantly compromise the quality of life in the global population. Although many strategies are needed to repair articular cartilage, including microfracture, autologous osteochondral transplantation, and osteochondral allograft, the therapeutic effects remain suboptimal. In recent years, with the development of cartilage tissue engineering, scientists have continuously improved the formulations of therapeutic cells, biomaterial-based scaffolds, and biological factors, which have opened new avenues for better therapeutics of cartilage lesions. This review focuses on advances in cartilage tissue engineering, particularly in preclinical trials and clinical applications, prospects, and challenges.