CircRNA CDR1as affects functional repair after spinal cord injury and regulates fibrosis through the SMAD pathway.

Spinal cord injury (SCI) is a complex problem in modern medicine. Fibroblast activation and fibroscarring after SCI impede nerve recovery. Non-coding RNA plays an important role in the progression of many diseases, but the study of its role in the progression of spinal fibrosis is still emerging. Here, we investigated the function of circular RNAs, specifically antisense to the cerebellar degeneration-related protein 1 (CDR1as), in spinal fibrosis and characterized its molecular mechanism and pathophysiology. The presence of CDR1as in the spinal cord was verified by sequencing and RNA expression assays. The effects of inhibition of CDR1as on scar formation, inflammation and nerve regeneration after spinal cord injury were investigated in vivo and in vitro. Further, gene expression of miR-7a-5p and protein expression of transforming Growth Factor Beta Receptor II (TGF-ßR2) were measured to evaluate their predicted interactions with CDR1as. The regulatory effects and activation pathways were subsequently verified by miR-7a-5p inhibitor and siCDR1as. These results indicate that CDR1as/miR-7a-5p/TGF-ßR2 interactions may exert scars and nerves functions and suggest potential therapeutic targets for treating spinal fibrotic diseases.

3D printing of customized bioceramics for promoting bone tissue regeneration by regulating sympathetic nerve behavior.

Numerous studies have shown that there are multiple neural activities involved in the process of bone resorption and bone regeneration, and promoting osteogenesis by promoting neural network reconstruction is an effective strategy for repairing critical size bone defects. However, traumatic bone defects often cause activation of the sympathetic nervous system (SNS) in the damaged area, releasing excess catecholamines (CAs), resulting in a decrease in the rate of bone formation. Herein, a 3D-printed scaffold loaded with propranolol (PRN) is proposed to reduce CA concentrations in bone defect areas and promote bone regeneration through drug release. For this purpose, PRN-loaded methacrylated gelatin (GelMA) microspheres were mixed with low-concentration GelMA and perfused into a 3D-printed porous hydroxyapatite (HAp) scaffold. By releasing PRN, which can block ß-adrenergic receptors, it hinders the activation of sympathetic nerves and inhibits the release of excess CA by the SNS. At the same time, the composite scaffold recruits bone marrow mesenchymal stem cells (BMSCs) and promotes the differentiation of BMSCs in the direction of osteoblasts, which effectively promotes bone regeneration in the rabbit femoral condyle defect model. The results of the study showed that the release of PRN from the composite scaffold could effectively hinder the activation of sympathetic nerves and promote bone regeneration, providing a new strategy for the treatment of bone defects.

DLP Fabrication of Multiple Hierarchical Biomimetic GelMA/SilMA/HAp Scaffolds for Enhancing Bone Regeneration.

Severe bone defects resulting from trauma and diseases remain a persistent clinical challenge. In this study, a hierarchical biomimetic microporous hydrogel composite scaffold was constructed by mimicking the hierarchical structure of bone. Initially, gelatin methacrylamide (GelMA) and methacrylic anhydride silk fibroin (SilMA) were synthesized, and GelMA/SilMA inks with suitable rheological and mechanical properties were prepared. Biomimetic micropores were then generated by using an aqueous two-phase emulsification method. Subsequently, biomimetic microporous GelMA/SilMA was mixed with hydroxyapatite (HAp) to prepare biomimetic microporous GelMA/SilMA/HAp ink. Hierarchical biomimetic microporous GelMA/SilMA/HAp (M-GSH) scaffolds were then fabricated through digital light processing (DLP) 3D printing. Finally, in vitro experiments were conducted to investigate cell adhesion, proliferation, and inward migration as well as osteogenic differentiation and vascular regeneration effects. In vivo experiments indicated that the biomimetic microporous scaffold significantly promoted tissue integration and bone regeneration after 12 weeks of implantation, achieving 42.39% bone volume fraction regeneration. In summary, this hierarchical biomimetic microporous scaffold provides a promising strategy for the repair and treatment of bone defects.

Fused Deposition Modeling Printed PLA/Nano ß-TCP Composite Bone Tissue Engineering Scaffolds for Promoting Osteogenic Induction Function.

Purpose: Large bone defects caused by congenital defects, infections, degenerative diseases, trauma, and tumors often require personalized shapes and rapid reconstruction of the bone tissue. Three-dimensional (3D)-printed bone tissue engineering scaffolds exhibit promising application potential. Fused deposition modeling (FDM) technology can flexibly select and prepare printed biomaterials and design and fabricate bionic microstructures to promote personalized large bone defect repair. FDM-3D printing technology was used to prepare polylactic acid (PLA)/nano ß-tricalcium phosphate (TCP) composite bone tissue engineering scaffolds in this study. The ability of the bone-tissue-engineered scaffold to repair bone defects was evaluated in vivo and in vitro. Methods: PLA/nano-TCP composite bone tissue engineering scaffolds were prepared using FDM-3D printing technology. The characterization data of the scaffolds were obtained using relevant detection methods. The physical and chemical properties, biocompatibility, and in vitro osteogenic capacity of the scaffolds were investigated, and their bone repair capacity was evaluated using an in vivo animal model of rabbit femur bone defects. Results: The FDM-printed PLA/nano ß-TCP composite scaffolds exhibited good personalized porosity and shape, and their osteogenic ability, biocompatibility, and bone repair ability in vivo were superior to those of pure PLA. The merits of biodegradable PLA and bioactive nano ß-TCP ceramics were combined to improve the overall biological performance of the composites. Conclusion: The FDM-printed PLA/nano-ß-TCP composite scaffold with a ratio of 7:3 exhibited good personalized porosity and shape, as well as good osteogenic ability, biocompatibility, and bone repair ability. This study provides a promising strategy for treating large bone defects.

Rationale and design of the optimal antithrombotic treatment for acute coronary syndrome patients with concomitant atrial fibrillation and implanted with new-generation drug-eluting stent: OPtimal management of anTIthroMbotic Agents (OPTIMA)-4 trial.

BACKGROUND: About 5%-15% of acute coronary syndrome (ACS) patients undergoing stent implantation have concomitant atrial fibrillation and need both antiplatelet and anticoagulant therapies. The optimal antithrombotic regimen remains uncertain in this scenario. HYPOTHESIS: A multicenter randomized controlled trial (OPtimal management of anTIthroMbotic Agents [OPTIMA]-4) is designed to test the hypothesis that, for ACS patients with concomitant nonvalvular atrial fibrillation (NVAF) and having low-to-moderate risk of bleeding, clopidogrel is comparable in efficacy but superior in safety compared to ticagrelor while being used in combination with dabigatran after new-generation drug-eluting stent (DES) implantation. METHODS: ACS patients who have low-to-moderate risk of bleeding (e.g., HAS-BLED score ≤ 2) and require anticoagulation therapy (CHA2 DS2 -VASc score ≥ 2) will be recruited after implantation of new-generation DES. A total of 1472 eligible patients will be randomly assigned to receive a 12-month dual antithrombotic treatment of either clopidogrel 75 mg daily or ticagrelor 90 mg twice daily in combination with dabigatran 110 mg twice daily. Participants will be followed up for 12 months after randomization. The primary efficacy endpoint is a composite of cardiovascular death, myocardial infarction, unplanned revascularization, ischemic stroke, and systemic thromboembolism. The primary safety endpoint is set as major bleeding or clinically relevant nonmajor bleeding defined by the International Society of Thrombosis and Hemostasis. The enrollment and follow-up have been launched. RESULTS: The first enrollment occurred on March 12, 2018. The recruitment is anticipated to be completed before December 31, 2024. CONCLUSIONS: The OPTIMA-4 trial offers an opportunity to assess the optimal dual antithrombotic regimen in ACS patients with concomitant NVAF after the implantation of new-generation DES.

DLP fabrication of customized porous bioceramics with osteoinduction ability for remote isolation bone regeneration.

Currently, various bioceramics have been widely used in bone regeneration. However, it remains a huge challenge to remote isolation bone regeneration, such as severed finger regeneration. The remote isolation bone tissue has a poor regenerative microenvironment that lacks enough blood and nutrition supply. It is very difficult to repair and regenerate. In this study, well-controlled multi-level porous 3D-printed calcium phosphate (CaP) bioceramic scaffolds with precision customized structures were fabricated by high-resolution digital light projection (DLP) printing technology for remote isolation bone regeneration. In vitro results demonstrated that optimizing material processing procedures could achieve multi-level control of 3D-printed CaP bioceramic scaffolds and enhance the osteoinduction ability of bioceramics effectively. In vivo results indicated that 3D-printed CaP bioceramic scaffolds constructed by optimized processing procedure exhibited a promising ability of bone regeneration and osteoinduction in ectopic osteogenesis and in situ caudal vertebrae regeneration in beagles. This study provided a promising strategy based on 3D-printed CaP bioceramic scaffolds constructed by optimized processing procedures for remote isolation bone regeneration, such as severed finger regeneration.

Preparation of BMP-2/PDA-BCP Bioceramic Scaffold by DLP 3D Printing and its Ability for Inducing Continuous Bone Formation.

Digital light processing (DLP)-based 3D printing is suitable to fabricate bone scaffolds with small size and high precision. However, the published literature mainly deals with the fabrication procedure and parameters of DLP printed bioceramic scaffold, but lacks the subsequent systematic biological evaluations for bone regeneration application. In this work, a biphasic calcium phosphate (BCP) macroporous scaffold was constructed by DLP-based 3D printing technique. Furthermore, bone morphogenetic protein-2 (BMP-2) was facilely incorporated into this scaffold through a facile polydopamine (PDA) modification process. The resultant scaffold presents an interconnected porous structure with pore size of ∼570 µm, compressive strength (∼3.6 MPa), and the self-assembly Ca-P/PDA nanocoating exhibited excellent sustained-release property for BMP-2. Notably, this BMP-2/PDA-BCP scaffold presents favorable effects on the adhesion, proliferation, osteogenic differentiation, and mineralization of bone marrow stromal cells (BMSCs). Furthermore, in vivo experiments conducted on rats demonstrated that the scaffolds could induce cell layer aggregation adjacent to the scaffolds and continuous new bone generation within the scaffold. Collectively, this work demonstrated that the BMP-2/PDA-BCP scaffold is of immense potential to treat small craniofacial bone defects in demand of high accuracy.

A 3D-printed biphasic calcium phosphate scaffold loaded with platelet lysate/gelatin methacrylate to promote vascularization.

3D-printed biphasic calcium phosphate (BCP) scaffolds show great clinical application potential in bone tissue engineering; however, vascularization of the scaffold is a crucial step for bone regeneration and is still difficult to be controlled. To enhance scaffold vascularization, a novel bioactive scaffold loaded with platelet lysate/gelatin methacrylate (PL/GelMA) in a BCP scaffold was proposed for promoting vascularization. The PL/GelMA/BCP scaffold was successfully prepared via digital light processing (DLP) printing and filled with PL/GelMA to promote the vascularization effect. In vitro evaluation indicated that human umbilical vein endothelial cells (HUVECs) adhered well on the PL/GelMA/BCP scaffold, and cell proliferation was significantly promoted by coculture with the scaffold. Moreover, a variety of growth factors (GFs) in the PL were detected which were slowly released from the scaffold to modulate the cell behaviour and promote the formation of blood vessel-like structures. Co-culturing with the PL/GelMA/BCP scaffold upregulated the expression of angiogenesis-related genes in cells. In vitro results showed that a higher capillary formation was also observed in PL/GelMA/BCP scaffolds implanted subcutaneously on the back of the rats. These results indicated that the vascularization ability of BCP was enhanced by filling it with PL/GelMA. The PL/GelMA/BCP scaffold has the potential to promote vascularization in tissue engineering.

Three-Dimensional Printing of Large-Scale, High-Resolution Bioceramics with Micronano Inner Porosity and Customized Surface Characterization Design for Bone Regeneration.

Three-dimensional printing technologies have opened up new possibilities for manufacturing bioceramics with complex shapes in a completely digital fabrication process. Some bioceramics have demonstrated elaborate design and high resolution in their small parts through digital light projection (DLP) printing. However, it is still a challenge to prepare large-scale, high-precision ceramics that can effectively regulate the bioactivity of materials. In this study, we fabricated a large-scale hydroxyapatite porous bioceramic (length >150 mm) using DLP. This bioceramic had highly micronanoporous surface structures (printing resolution <65 µm), which could be controlled by adjusting the solid content and sintering process. Both in vitro and in vivo results indicated that the designed bioceramic had promising bone regeneration ability. This study provides significant evidence for exploring the effects of microenvironments on bone tissue regeneration. These results indicated that DLP technology has the potential to produce large-scale bone tissue engineering scaffolds with accurate porosity.

Crystal structures of the SARS-CoV-2 nucleocapsid protein C-terminal domain and development of nucleocapsid-targeting nanobodies.

The ongoing outbreak of COVID-19 caused by SARS-CoV-2 has resulted in a serious public health threat globally. Nucleocapsid protein is a major structural protein of SARS-CoV-2 that plays important roles in the viral RNA packing, replication, assembly, and infection. Here, we report two crystal structures of nucleocapsid protein C-terminal domain (CTD) at resolutions of 2.0 Å and 3.1 Å, respectively. These two structures, crystallized under different conditions, contain 2 and 12 CTDs in asymmetric unit, respectively. Interestingly, despite different crystal packing, both structures show a similar dimeric form as the smallest unit, consistent with its solution form measured by the size-exclusion chromatography, suggesting an important role of CTD in the dimerization of nucleocapsid proteins. By analyzing the surface charge distribution, we identified a stretch of positively charged residues between Lys257 and Arg262 that are involved in RNA-binding. Through screening a single-domain antibodies (sdAbs) library, we identified four sdAbs targeting different regions of nucleocapsid protein with high affinities that have future potential to be used in viral detection and therapeutic purposes.

Dissipative Kerr single soliton generation with extremely high probability via spectral mode depletion.

Optical Kerr solitons generation based on microresonators is essential in nonlinear optics. Among various soliton generation processes, the single soliton generation plays a pivotal role since it ensures rigorous mode-locking on each comb line whose interval equals the free spectral range (FSR) of the microresonator. Current studies show that single soliton generation is challenging due to cavity instability. Here, we propose a new method to greatly improve single soliton generation probalility in the anomalous group velocity dispersion (GVD) regime in a micro-ring resonator based on silicon nitride. The improvement is realized by introducing mode depletion through an integrated coupled filter. It is convenient to introduce controllable single mode depletion in a micro-ring resonator by adjusting the response function of a coupled filter. We show that spectral mode depletion (SMD) can significantly boost the single soliton generation probability. The effect of SMD on the dynamics of optical Kerr solitons generation are also discussed. The proposed method offers a straightforward and simple way to facilitate robust single soliton generation, and will have an impact on the research development in optical Kerr soliton generation and on-chip optical frequency mode manipulation.

Chondrocyte-laden GelMA hydrogel combined with 3D printed PLA scaffolds for auricle regeneration.

The current gold standard for auricular reconstruction after microtia or ear trauma is the autologous cartilage graft with an autologous skin flap overlay. Harvesting autologous cartilage requires an additional surgery that may result in donor area complications. In addition, autologous cartilage is limited and the auricular reconstruction requires complex sculpting, which requires excellent clinical skill and is very time consuming. This work explores the use of 3D printing technology to fabricate bioactive artificial auricular cartilage using chondrocyte-laden gelatin methacrylate (GelMA) and polylactic acid (PLA) for auricle reconstruction. In this study, chondrocytes were loaded within GelMA hydrogel and combined with the 3D-printed PLA scaffolds to biomimetic the biological mechanical properties and personalized shape. The printing accuracy personalized scaffolds, biomechanics and chondrocyte viability and biofunction of artificial auricle have been studied. It was found that chondrocytes were fixed in the PLA auricle scaffolds via GelMA hydrogels and exhibited good proliferative properties and cellular activity. In addition, new chondrocytes and chondrogenic matrix, as well as type II collagen were observed after 8 weeks of implantation. At the same time, the transplanted auricle complex kept full and delicate auricle shape. This study demonstrates the potential of using 3D printing technology to construct in vitro living auricle tissue. It shows a great prospect in the clinical application of auricle regeneration.

Biomineralization from the Perspective of Ion Aggregation: Calcium Phosphate Nucleation in the Physiological Environment.

Biomineralization is an important process of bone tissue generation. Calcium (Ca) and phosphate (P) ions aggregate and nucleate under the regulation of biomolecules at the initial mineralization stage. Due to the complexity of the physiological environment, the movement behavior and mineralization mechanism of calcium and phosphate ions, as well as the effect of biomolecules on them, are not clear. In this study, computer simulations and experimental verification were applied to investigate the characteristics of the initial biomineralization from the view of ion aggregation and nucleation. The results prove that P ions play a more important role in mineralization than Ca ions. The guanidyl group and surrounding carboxyl terminal groups are a potential excellent nucleation domain on proteins. The interval distribution of acidic/basic residues on protein is more conductive to the formation of large Ca and P ions clusters. The involvement of protein could increase the probability of hydroxyapatite phase precipitation, especially in the presence of a helical conformation. The detailed information on Ca and P ions behavior provided by the computer simulations is helpful for further understanding the mechanism of biomineralization, which will promote the development of bone repair materials to the biomimetic mineralized materials.

Integrated analysis of hypoxia-associated lncRNA signature to predict prognosis and immune microenvironment of lung adenocarcinoma patients.

Lung adenocarcinoma (LUAD) represents the main lung cancer (LC) subtype that possesses a disappointing clinical outcome over the decades. Tumor hypoxia is closely bound up with dismal survival for malignant tumor cases. We identified hypoxia-associated long non-coding RNA (lncRNA) signature to be an explicit indicator for predicting prognosis. The present work acquired RNA-seq and associated clinical data from The Cancer Genome Atlas (TCGA) database. Consensus cluster analysis characterized the hypoxia status of LUAD patients. Cox regression analysis with the least absolute shrinkage and selection operator (LASSO) method determined significantly prognosis-related lncRNAs which were used to create a prognostic model. Diverse statistical approaches like the Kaplan-Meier curve, receiver operating characteristic (ROC) curve, and nomogram were adopted to verify the accuracy of the risk score. The potential immune environment landscape was unearthed by the CIBERSORT algorithm. Three hypoxia-related clusters were determined and 221 differentially expressed hypoxia-related lncRNAs were screened out. We developed a new predictive model based on seven lncRNAs (LINC00941, AC022784.1, AC079949.2, LINC00707, AL161431.1, AC010980.2 and AC090001.1). Kaplan-Meier curves and ROC plots uncovered the reliable predictive power of the risk score model. In addition, the immunosuppressive landscape was presented in the high-risk group by immune cell infiltration analysis. The seven hypoxia lncRNAs survival signature in our article are robust, accurate tools for predicting overall survival in LUAD patients.

Fabrication of customized Ti6AI4V heterogeneous scaffolds with selective laser melting: Optimization of the architecture for orthopedic implant applications.

Orthopedic implants with heterogeneous porous structures were known as ideal bone osteointegration. This research introduced the selective laser melting (SLM), finite element analysis (FEA), and a hydrothermal process (HT) for manufacturing a three-level heterogeneous porous structure. The macroporous structure was designed via CAD and micropores were tuned via laser power regulation. A nano-size layer of hydroxyapatite crystals was coated by an HT process. The mechanical properties were reinforced via a core-shell structure with core reinforcement. The existence of micropores and nano-hydroxyapatite coating enhanced the in vitro proliferation of preosteoblasts and osteogenic cellular behaviors of rBMSCs. Thus, the three-level heterogeneous porous titanium implants could inspire researchers with potential clue of cyto-implant interaction mechanism, therefore building ideal orthopedic implants with accelerated osteointegration. STATEMENT OF SIGNIFICANCE: Porous structures of titanium implants play an important role in bone tissue regeneration; The geometrical environment influence cell behaviour and bone tissue ingrowth in all macro-/micro-/nanoscale. In this study, a novel method to fabricate heterogeneous scaffolds and its macro-/micro-/nanoscopic structures were studied. A CAD model was used to obtain the macroscopic structure and the insufficient laser power was introduced for porous microstructure. Therefore, a layer of nano hydroxyapatite was coated via hydrothermal process. Cytoproliferation and cytodifferentiation results indicated that a integrity of regular/irregular, macro-/micro-/nanoscale porous structure had advance in recruiting stem cells and promoting differentiation. This research is beneficial to the development of bone implants with better bone regeneration ability.

Construction of Biomimetic Natural Wood Hierarchical Porous-Structure Bioceramic with Micro/Nanowhisker Coating to Modulate Cellular Behavior and Osteoinductive Activity.

Scaffolds with a biomimetic hierarchy micro/nanoscale pores play an important role in bone tissue regeneration. In this study, multilevel porous calcium phosphate (CaP) bioceramic orthopedic implants were constructed to mimic the micro/nanostructural hierarchy in natural wood. The biomimetic hierarchical porous scaffolds were fabricated by combining three-dimensional (3D) printing technology and hydrothermal treatment. The first-level macropores (∼100-600 µm) for promoting bone tissue ingrowth were precisely designed using a set of 3D printing parameters. The second-level micro/nanoscale pores (∼100-10,000 nm) in the scaffolds were obtained by hydrothermal treatment to promote nutrient/metabolite transportation. Micro- and nanoscale-sized pores in the scaffolds were recognized as in situ formation of whiskers, where the shape, diameter, and length of whiskers were modulated by adjusting the components of calcium phosphate ceramics and hydrothermal treatment parameters. These biomimetic natural wood-like hierarchical structured scaffolds demonstrated unique physical and biological properties. Hydrophilicity and the protein adsorption rate were characterized in these scaffolds. In vitro studies have identified micro/nanowhisker coating as potent modulators of cellular behavior through the onset of focal adhesion formation. In addition, histological results indicate that biomimetic scaffolds with porous natural wood hierarchical pores exhibited good osteoinductive activity. In conclusion, these findings combined suggested that micro/nanowhisker coating is a critical factor to modulate cellular behavior and osteoinductive activity.

3D printed titanium scaffolds with homogeneous diamond-like structures mimicking that of the osteocyte microenvironment and its bone regeneration study.

Biofabrication of personalized titanium scaffold mimicking that of the osteocyte microenvironment is challenging due to its complex geometrical cues. The effect of scaffolds geometrical cues and implantation sites on osteogenesis is still not clear. In this study, personalized titanium scaffolds with homogeneous diamond-like structures mimicking that of the osteocyte microenvironment were precisely designed and fabricated by selected laser melting method. The effects of different geometric cues, including porosity, pore sizes and interconnection properties, on cellular behavior were investigated. Biomimetic mechanical properties of porous titanium alloy scaffold were predesigned and simulated by finite element analysis.In vitroexperiment revealed that homogeneous diamond-like structures mimicking that of the osteocyte microenvironment triggered osteocyte adhesion and migration behavior. Typical implantation sites, including rabbit femur, beagle femur, and beagle skull, were used to study the implantation sites effects on bone regeneration.In vivoexperimental results indicated that different implantation sites showed significant differences. This study helps to understand the scaffolds geometrical microenvironment and implantation sites effects on osteogenesis mechanism. And it is beneficial to the development of bone implants with better bone regeneration ability.

Arthroscopic treatment of synovial chondromatosis of hip joint.

PURPOSE: This retrospective study summarized the clinical, radiographic, and arthroscopic manifestation of synovial chondromatosis (SC) of the hip, along with the post-operative effect to discuss the curative effect of arthroscopic management of hip SC. METHODS: Twenty-one patients who underwent arthroscopic surgery from the same surgeon for hip SC were followed up for an average of 45 months. T-shaped capsulotomy was routinely performed in each case. Visual analog scale, range of motion, modified Harris Hip Score, and International Hip Outcome Tool score were collected preoperatively and at the time of the latest follow-up. All patients' demographics, radiographs, and arthroscopic images were collected to summarize and conclude the similarities and differences of their manifestation. RESULTS: Large wedged clumps of loose bodies demonstrated distinguishable radiographic, arthroscopic appearance and demanded a different surgical strategy. Postoperative scores were all significantly improved. One case of residual pain and two cases of residual loose bodies with no symptom related were reported at the final follow-up. All but one patient were satisfied with the outcome. CONCLUSION: Arthroscopy treatment of hip SC with T-shaped capsulotomy has demonstrated a good result in terms of clinical outcome score, recurrence rate, and complication rate. On the basis of this study, we concluded the clinical performance of large wedged clumps of loose bodies of hip SC.

Rhein laden pH-responsive polymeric nanoparticles for treatment of osteoarthritis.

Osteoarthritis (OA) is a condition associated with severe inflammation, cartilage destruction and degeneration of joints. Rhein (Rh) is an effective anti-inflammatory drug with proven efficacy in in-vitro and in-vivo models. pH sensitive Rh and NH4HCO3 laden poly (lactic-co-glycolic acid (PLGA) nanoparticles (NPs) (Rh-PLGA-NPs@NH4) are developed for an effective treatment of OA. The Rh-PLGA-NPs@NH4 are prepared along with Rh-PLGA-NPs as a control by double emulsion method. Rh-PLGA-NPs@NH4 was characterized for their size, shape, morphology and encapsulation efficiency (EE). The effect of pH on release of Rh from Rh-PLGA-NPs@NH4 was studied at different pH. Further, the cytotoxicity effect of Rh-PLGA-NPs@NH4 on THP-1 cells were evaluated. Anti-inflammatory efficacy was evaluated on LPS stimulated THP-1 cells and the release of pro-inflammatory cytokines was evaluated and compared with control. The size of Rh-PLGA-NPs@NH4 and Rh-PLGA-NPs was found to be 190.7 ± 1.2 nm and 134.6 ± 2.4 nm respectively with poly dispersity (PDI) 0.14 and 0.15. The zeta potential of Rh-PLGA-NPs@NH4 was found to be -22 ± 1.12 mV. Rh-PLGA-NPs@NH4 were uniform, smooth and spherical shape as confirmed using electron microscopy analysis. Rh-PLGA-NPs@NH4 release the Rh more effectively in the low pH of synovial fluid environment (SFE). Rh-PLGA-NPs@NH4 also significantly affect inflammatory cytokines TNF-α and IL-1ß and reduced their release in LPS stimulated THP-1 cells. Reactive oxygen species (ROS), a mediator responsible for the cartilage collapse was also found to be reduced. Results proposes that Rh-PLGA-NPs could provide therapeutic solution to those patients who suffer from chronic joint ailments by reducing the progression of OA.