Meta-analysis of Rapid Rehabilitation Surgery in Hip and Knee Replacement.

Context: Total knee arthroplasty (TKA) and total hip arthroplasty (THA) have become well-established and standardized procedures. However, complications can easily occur, such as joint pain and swelling, due to the high trauma of surgery and intraoperative blood loss, which can affect patients' recovery. A treatment that can effectively shorten postoperative recovery time and reduce complications is key to the perioperative treatment of TKA and THA. Objective: The study aimed to evaluate the efficacy of the Rapid Rehabilitation Surgery (RRS) protocol, an enhanced recovery after surgery (ERAS) approach, for TKA and THA to substantiate its application by the current research team. Design: The research team performed a narrative review by searching the Excerpta Medica Database (Embase), the Kirkland database, the China National Knowledge Infrastructure (CNKI), the Wanfang database, and the VIP database, using the keywords rapid rehabilitation surgery, hip replacement, knee replacement, and perioperative period, and randomized controlled trials or randomized controlled trials (RCTs) or clinical trials. The team also performed a meta-analysis of the data from the studies that the search found. Setting: The study took place at Yulin No. 2 Hospital, Yulin, China. Participants: The studies included 1673 patients in six studies that conducted RCTs, including 565 patients who received ERAS and 1108 patients who received RCTS. Outcome Measures: The research team used Cochrane software for risk assessment for the included studies. For the meta-analysis, the team examined the included studies' data related: (1) to length of hospital stay, (2) to postoperative complications, (3) to blood-transfusion rate, and (4) to postoperative pain. Results: The ERAS nursing reduced the mean length of hospital stay by 2.17 days compared to that of the combined control groups from five studies (MD=-2.17, 95% CI [3.36-0.99], P < .01). In the analysis of four studies, the incidence of surgical complications was 9.1% lower in the combined intervention groups than in the combined control groups (r=0.30, 95% CI [0.10 to 0.94], P = .02). Conclusions: RRS is a safe and effective method of treating patients undergoing THA and TKA and can significantly reduce hospitalization time and postoperative complications. This approach deserves promotion.

Injectable Antimicrobial Conductive Hydrogels for Wound Disinfection and Infectious Wound Healing.

As the abuse of antibiotics continues to increase, the emergence of antibiotic resistance and unknown drug-resistant bacterial infections pose a great threat on people worldwide. In this work, we aimed to develop a series of injectable antimicrobial conductive hydrogels based on glycidyl methacrylate functionalized quaternized chitosan (QCSG), gelatin methacrylate (GM), and graphene oxide (GO) for drug-resistant bacterial disinfection and infectious wound healing. The rheology, morphology, mechanical properties, and electrical and photothermal properties of the hydrogels were characterized. Furthermore, the good in vitro and in vivo intrinsic antibacterial, photothermal antibacterial, and antibiotics released antibacterial properties of this multiantibacterial hydrogel were verified. The good biocompatibility of these hydrogels was also investigated by cytocompatibility, hemocompatibility, and histocompatibility tests. In the drug-resistant Methicillin-resistant Staphylococcus aureus (MRSA) infected mouse full-thickness defect model, the wound closure rate, the length of dermal tissue gap, number of blood vessels and hair follicles in hematoxylin-eosin (HE) staining, the amount of collagen in Masson staining, and the related cytokines for the expression of inflammation (interleukin-6, IL-6) and regeneration of blood vessels (vascular endothelial growth factor, VEGF) in immunofluorescence were all further studied. All the results demonstrated the better wound healing effect of these multiantibacterial injectable conductive hydrogel in infectious skin tissue defect repair, indicating their great potential for infected wound healing.

SUMO-modified bone marrow mesenchymal stem cells promoted the repair of articular cartilage in rats.

Articular cartilage damage can lead to joint deformity, pain, and severe dysfunction. However, due to the lack of blood vessels and nerves in articular cartilage, the self-healing capacity of damaged cartilage is limited. In this study, we overexpressed small ubiquitin-like modifier (SUMO)1, SUMO2/3, and SUMO1/2/3 in bone marrow mesenchymal stem cells (BMSCs). Then, these cells were inoculated on surfaces of different hardness, and their differentiation into chondrocytes, hypoxic tolerance ability, and inflammatory response was detected. Finally, BMSCs were transplanted into the injured knee joint cavity of the rats, and the repair was evaluated. We found that BMSCs overexpressing SUMO1 were more likely to differentiate into articular cartilage along with the hardness of the surface, while BMSCs overexpressing SUMO2/3 could reduce inflammation response and improve the damaged cartilage microenvironment. In the rat model, BMSCs overexpressing SUMO1/2/3 transplanted on injured articular cartilage surface showed better survival, less inflammatory response, and improved tissue repair capability. In conclusion, BMSCs overexpressing SUMO are more tolerant to hypoxia conditions, and have stronger repair ability for damaged chondrocytes in vitro and for articular cartilage injury model in rats, and are excellent seed cells for repairing articular cartilage.

Adhesive Hemostatic Conducting Injectable Composite Hydrogels with Sustained Drug Release and Photothermal Antibacterial Activity to Promote Full-Thickness Skin Regeneration During Wound Healing.

Developing injectable nanocomposite conductive hydrogel dressings with multifunctions including adhesiveness, antibacterial, and radical scavenging ability and good mechanical property to enhance full-thickness skin wound regeneration is highly desirable in clinical application. Herein, a series of adhesive hemostatic antioxidant conductive photothermal antibacterial hydrogels based on hyaluronic acid-graft-dopamine and reduced graphene oxide (rGO) using a H2 O2 /HPR (horseradish peroxidase) system are prepared for wound dressing. These hydrogels exhibit high swelling, degradability, tunable rheological property, and similar or superior mechanical properties to human skin. The polydopamine endowed antioxidant activity, tissue adhesiveness and hemostatic ability, self-healing ability, conductivity, and NIR irradiation enhanced in vivo antibacterial behavior of the hydrogels are investigated. Moreover, drug release and zone of inhibition tests confirm sustained drug release capacity of the hydrogels. Furthermore, the hydrogel dressings significantly enhance vascularization by upregulating growth factor expression of CD31 and improve the granulation tissue thickness and collagen deposition, all of which promote wound closure and contribute to a better therapeutic effect than the commercial Tegaderm films group in a mouse full-thickness wounds model. In summary, these adhesive hemostatic antioxidative conductive hydrogels with sustained drug release property to promote complete skin regeneration are an excellent wound dressing for full-thickness skin repair.

Honokiol improved chondrogenesis and suppressed inflammation in human umbilical cord derived mesenchymal stem cells via blocking nuclear factor-κB pathway.

BACKGROUND: Cartilage degradation is the significant pathological process in osteoarthritis (OA). Inflammatory cytokines, such as interleukin-1ß (IL-1ß), activate various downstream mediators contributing to OA pathology. Recently, stem cell-based cartilage repair emerges as a potential therapeutic strategy that being widely studied, whereas, the outcome is still far from clinical application. In this study, we focused on an anti-inflammatory agent, honokiol, which is isolated from an herb, investigated the potential effects on human umbilical cord derived mesenchymal stem cells (hUC-MSCs) in IL-1ß stimulation. METHODS: Second passage hUC-MSCs were cultured for multi-differentiation. Flow cytometry, qRT-PCR, von Kossa stain, alcian blue stain and oil red O stain were used for characterization and multi-differentiation determination. Honokiol (5, 10, 25, 50 µM) and IL-1ß (10 ng/ml) were applied in hUC-MSCs during chondrogenesis. Analysis was performed by MTT, cell apoptosis evaluation, ELISA assay, qRT-PCR and western blot. RESULTS: hUC-MSC was positive for CD73, CD90 and CD105, but lack of CD34 and CD45. Remarkable osteogenesis, chondrogenesis and adipogenesis were detected in hUC-MSCs. IL-1ß enhanced cell apoptosis and necrosis and activated the expression of caspase-3, cyclooxygenase-2 (COX-2), interleukin-6 (IL-6) and matrix metalloproteinase (MMP)-1, -9, 13 in hUC-MSCs. Moreover, the expression of SRY-related high-mobility group box 9 (SOX-9), aggrecan and col2α1 was suppressed. Honokiol relieved these negative impacts induced by IL-1ß and suppressed Nuclear factor-κB (NF-κB) pathway by downregulating expression of p-IKKα/ß, p-IκBα and p-p65 in dose-dependent and time-dependent manner. CONCLUSIONS: Honokiol improved cell survival and chondrogenesis of hUC-MSCs and inhibited IL-1ß-induced inflammatory response, which suggested that combination of anti-inflammation and stem cell can be a novel strategy for better cartilage repair.

Lentivirus-TAZ Administration Alleviates Osteoporotic Phenotypes in the Femoral Neck of Ovariectomized Rats.

BACKGROUND: Osteoporosis is characterized by impairment of bone mass, strength, and microarchitecture, leading to the susceptibility to fragility fractures, especially in femoral neck region. Transcriptional coactivator with PDZ-binding motif (TAZ) facilitates osteogenesis while suppressing adipogenesis via regulation of transcriptional activities of runt-related transcription factor 2 and peroxisome proliferator-activated receptor x03B3;. Here, we validated the role of TAZ in vivo using an ovariectomized (OVX) rat model of osteoporosis. METHODS: Serum alkaline phosphatase, triglyceride, cholesterol and urinary hydroxyproline were measured on an automatic analyzer using diagnostic reagent kits. Serum OCN and C-terminal cross-linked telopeptides of type I collagen were measured using ELISA. Bone mineral density was measured using dual-energy X-ray scanner. Mechanical parameters were detected by three-point bending assays. Bone volume per tissue volume (BV/TV), trabecular thickness (Tb. Th), trabecular number (Tb. No), and trabecular separation (Tb. Sp) were measured by MicroCT. The mRNA and protein levels were quantified by Realtime PCR and Western Blotting respectively. RESULTS: After injections of lentivirus overexpressing TAZ into the femoral neck region, bone mineral density, ultimate force, stiffness, BV/TV, Tb. Th, and Tb. No were significantly increased, whereas Tb. Sp was dramatically decreased. In the TAZ-overexpression region in the femoral neck of OVX rats, the mRNA levels of Runx2 and osteocalcin were obviously elevated, whereas that of PPARx03B3; and adipocyte protein 2 were downregulated. CONCLUSION: Lentivirus-mediated TAZ gene therapy alleviated the osteoporotic phenotypes in the femoral neck of OVX rats, providing an alternative strategy for the treatment of postmenopausal osteoporosis and prevention of osteoporotic fracture.

Section of the anterior cruciate ligament in the rabbit as animal model for osteoarthritis progression.

PURPOSE: The purpose of this study was to determine whether instability of knee is a risk factor in the progression of osteoarthritis (OA). METHODS: Twenty-four mature New Zealand White rabbits were randomly divided into four groups. The control group received 0.3 ml saline in the first, fourth and seventh days in the right knee, while the other three groups received the same dosage 4 % papain and its activator 0.03 M L-cystein. The P3w group knees were harvested at three weeks after the last papain injection, the P6w group knees received a sham surgery at three weeks and were harvested at six weeks after the last papain injection, while the P+ACLT group knees received ACL transection at three weeks and were harvested at six weeks after the last papain injection. Cartilage degradation of femoral condyles and tibial plateaus were evaluated by X-rays, macroscopy, light microscopic and transmission electron microscopy (TEM). RESULTS: According to X-rays grade scale, macroscopic grade scale, light microscopic modified Mankin scale and TEM, in the P3w knees, cartilage degeneration of femoral condyles and tibial plateaus were significantly severe compared to those of the control group (P < 0.05), but the differences were not apparent in comparison with the P6w knees (P > 0.05). However, in P+ACLT knees, cartilage degeneration of femoral condyles and tibial plateaus appeared more severe in comparison with P6w knees, and the difference was significant (P < 0.05). CONCLUSIONS: Instability of knee plays a significant role in increasing the severity of cartilage degradation in rabbit knees and should be considered as a risk factor in OA knee progression. Our data may suggest that reconstruction of knee stability may prevent or delay the progression of OA.

Injectable Self-Expanding/Self-Propelling Hydrogel Adhesive with Procoagulant Activity and Rapid Gelation for Lethal Massive Hemorrhage Management.

Developing hydrogels that can quickly reach deep bleeding sites, adhere to wounds, and expand to stop lethal and/or noncompressible bleeding in civil and battlefield environments remains a challenge. Herein, an injectable, antibacterial, self-expanding, and self-propelling hydrogel bioadhesive with procoagulant activity and rapid gelation is reported. This hydrogel combines spontaneous gas foaming and rapid Schiff base crosslinking for lethal massive hemorrhage. Hydrogels have rapid gelation and expansion rate, high self-expanding ratio, excellent antibacterial activity, antioxidant efficiency, and tissue adhesion capacity. In addition, hydrogels have good cytocompatibility, procoagulant ability, and higher blood cell/platelet adhesion activity than commercial combat gauze and gelatin sponge. The optimized hydrogel (OD-C/QGQL-A30) exhibits better hemostatic ability than combat gauze and gelatin sponge in rat liver and femoral artery bleeding models, rabbit volumetric liver loss massive bleeding models with/without anticoagulant, and rabbit liver and kidney incision bleeding models with bleeding site not visible. Especially, OD-C/QGQL-A30 rapidly stops the bleedings from pelvic area of rabbit, and swine subclavian artery vein transection. Furthermore, OD-C/QGQL-A30 has biodegradability and biocompatibility, and accelerates Methicillin-resistant S. aureus (MRSA)-infected skin wound healing. This injectable, antibacterial, self-expanding, and self-propelling hydrogel opens up a new avenue to develop hemostats for lethal massive bleeding, abdominal organ bleeding, and bleeding from coagulation lesions.

[Research progress of magnesium and magnesium alloy implants in sports medicine].

Objective: To review the research progress of magnesium and magnesium alloy implants in the repair and reconstruction of sports injury. Methods: Relevant literature of magnesium and magnesium alloys for sports injury repair and reconstruction was extensively reviewed. The characteristics of magnesium and its alloys and their applications in the repair and reconstruction of sports injuries across various anatomical sites were thoroughly discussed and summarized. Results: Magnesium and magnesium alloys have advantages in mechanical properties, biosafety, and promoting tendon-bone interface healing. Many preclinical studies on magnesium and magnesium alloy implants for repairing and reconstructing sports injuries have yielded promising results. However, successful clinical translation still requires addressing issues related to mechanical strength and degradation behavior, where alloying and surface treatments offer feasible solutions. Conclusion: The clinical translation of magnesium and magnesium alloy implants for repairing and reconstructing sports injuries holds promise. Subsequent efforts should focus on optimizing the mechanical strength and degradation behavior of magnesium and magnesium alloy implants. Conducting larger-scale biocompatibility testing and developing novel magnesium-containing implants represent new directions for future research.

Injectable Bioadhesive Photocrosslinkable Hydrogels with Sustained Release of Kartogenin to Promote Chondrogenic Differentiation and Partial-Thickness Cartilage Defects Repair.

Partial-thickness cartilage defect (PTCD) is a common and formidable clinical challenge without effective therapeutic approaches. The inherent anti-adhesive characteristics of the extracellular matrix within cartilage pose a significant impediment to the integration of cells or biomaterials with the native cartilage during cartilage repair. Here, an injectable photocrosslinked bioadhesive hydrogel, consisting of gelatin methacryloyl (GM), acryloyl-6-aminocaproic acid-g-N-hydroxysuccinimide (AN), and poly(lactic-co-glycolic acid) microspheres loaded with kartogenin (KGN) (abbreviated as GM/AN/KGN hydrogel), is designed to enhance interfacial integration and repair of PTCD. After injected in situ at the irregular defect, a stable and robust hydrogel network is rapidly formed by ultraviolet irradiation, and it can be quickly and tightly adhered to native cartilage through amide bonds. The hydrogel exhibits good adhesion strength up to 27.25 ± 1.22 kPa by lap shear strength experiments. The GM/AN/KGN hydrogel demonstrates good adhesion, low swelling, resistance to fatigue, biocompatibility, and chondrogenesis properties in vitro. A rat model with PTCD exhibits restoration of a smoother surface, stable seamless integration, and abundant aggrecan and type II collagen production. The injectable stable adhesive hydrogel with long-term chondrogenic differentiation capacity shows great potential to facilitate repair of PTCD.

Epidemiological and clinical features, treatment status, and economic burden of traumatic spinal cord injury in China: a hospital-based retrospective study.

Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death. China has the largest population of patients with traumatic spinal cord injury. Previous studies of traumatic spinal cord injury in China have mostly been regional in scope; national-level studies have been rare. To the best of our knowledge, no national-level study of treatment status and economic burden has been performed. This retrospective study aimed to examine the epidemiological and clinical features, treatment status, and economic burden of traumatic spinal cord injury in China at the national level. We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China. Patient epidemiological and clinical features, treatment status, and total and daily costs were recorded. Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program. The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall (annual percentage change, -0.5% and 2.1%, respectively). A total of 10,053 (74.7%) patients underwent surgery. Only 2.8% of patients who underwent surgery did so within 24 hours of injury. A total of 2005 (14.9%) patients were treated with high-dose (≥ 500 mg) methylprednisolone sodium succinate/methylprednisolone (MPSS/MP); 615 (4.6%) received it within 8 hours. The total cost for acute traumatic spinal cord injury decreased over the study period (-4.7%), while daily cost did not significantly change (1.0% increase). Our findings indicate that public health initiatives should aim at improving hospitals' ability to complete early surgery within 24 hours, which is associated with improved sensorimotor recovery, increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.

Is cervical disc arthroplasty superior to fusion for treatment of symptomatic cervical disc disease? A meta-analysis.

BACKGROUND: As the current standard treatment for symptomatic cervical disc disease, anterior cervical decompression and fusion may result in progressive degeneration or disease of the adjacent segments. Cervical disc arthroplasty was theoretically designed to be an ideal substitute for fusion by preserving motion at the operative level and delaying adjacent level degeneration. However, it remains unclear whether arthroplasty achieves that aim. QUESTIONS/PURPOSES: We investigated whether cervical disc arthroplasty was associated with (1) better function (neck disability index, pain assessment, SF-36 mental and physical health surveys, neurologic status) than fusion, (2) a lower incidence of reoperation and major complications, and (3) a lower risk of subsequent adjacent segment degeneration. METHODS: We conducted a comprehensive search in MEDLINE(®), EMBASE, and Cochrane Central Register of Controlled Trials and identified 503 papers. Of these, we identified 13 reports from 10 randomized controlled trials involving 2227 patients. We performed a meta-analysis of functional scores, rates of reoperation, and major complications. The strength of evidence was evaluated by using GRADE profiler software. Of the 10 trials, six trials including five prospective multicenter FDA-regulated studies were sponsored by industry. The mean follow-ups of the 10 trials ranged from 1 to 5 years. RESULTS: Compared with anterior cervical decompression and fusion, cervical disc arthroplasty had better mean neck disability indexes (95% CI, -0.25 to -0.02), neurologic status (risk ratio [RR], 1.04; 95% CI, 1.00-1.08), with a reduced incidence of reoperation related to the index surgery (RR, 0.42; 95% CI, 0.22-0.79), and major surgical complications (RR, 0.45; 95% CI, 0.27-0.75) at a mean of 1 to 3 years. However, the operation rate at adjacent levels after two procedures was similar (95% CI, 0.31-1.27). The three studies with longer mean follow-ups of 4 to 5 years also showed similar superiority of all four parameters of cervical disc arthroplasty compared with fusion. CONCLUSIONS: For treating symptomatic cervical disc disease, cervical disc arthroplasty appears to provide better function, a lower incidence of reoperation related to index surgery at 1 to 5 years, and lower major complication rates compared with fusion. However, cervical disc arthroplasty did not reduce the reoperation rate attributable to adjacent segment degeneration than fusion. Further, it is unclear whether these differences in subsequent surgery including arthroplasty revisions will persist beyond 5 years.

Advanced glycation end products regulate the receptor of AGEs epigenetically.

Advanced glycation end-products (AGEs) can boost their receptor of AGE (RAGE) expression through the downstream signaling pathway to facilitate AGE-RAGE interaction. In this regulation process, the primary signaling pathways are NF-κB and STAT3. However, the inhibition of these transcription factors cannot completely block the upregulation of RAGE, which indicates AGEs may also impact RAGE expression via other pathways. In this study, we revealed that AGEs can exhibit epigenetic impacts on RAGE expression. Here, we used carboxymethyl-lysine (CML) and carboxyethyl-lysine (CEL) to treat liver cells and discovered that AGEs can promote the demethylation of the RAGE promoter region. To verify this epigenetic modification, we employed dCAS9-DNMT3a with sgRNA to specifically modify the RAGE promoter region against the effect of carboxymethyl-lysine and carboxyethyl-lysine. The elevated RAGE expressions were partially repressed after AGE-induced hypomethylation statuses were reversed. Additionally, TET1 were also upregulated in AGE-treated cells, indicating AGEs may epigenetically modulate RAGE through the elevating TET1 level.

Injectable Antiswelling and High-Strength Bioactive Hydrogels with a Wet Adhesion and Rapid Gelling Process to Promote Sutureless Wound Closure and Scar-free Repair of Infectious Wounds.

Developing injectable antiswelling and high-strength bioactive hydrogels with wet tissue adhesiveness and a rapid gelling process to meet the requirements for rapid hemostasis, sutureless wound closure, and scar-free repair of infected skin wounds continues to have ongoing challenges. Herein, injectable, antibacterial, and antioxidant hydrogel adhesives based on poly(citric acid-co-polyethylene glycol)-g-dopamine and amino-terminated Pluronic F127 (APF) micelles loaded with astragaloside IV (AS) are prepared. The H2O2/horseradish peroxidase (HRP) system is used to cause cross-linking of the hydrogel network through oxidative coupling between catechol groups and chemical cross-linking between the catechol group and the amino group. The hydrogels exhibit a rapid gelling process, high mechanical strength, an antiswelling effect, good antioxidant property, H2O2 release behavior, and degradability. In addition, the hydrogels present good wet tissue adhesiveness, high bursting pressure, excellent antibacterial activity, long-term sustained release of AS, and good biocompatibility. The hydrogels perform good hemostasis on mouse liver, rat liver, and rabbit femoral vein bleeding models and achieve much better closure and healing of skin incisions than biomedical glue and surgical sutures. Furthermore, the hydrogel dressing significantly improved the scar-free repair of MRSA-infected full thickness skin defect wounds by modulating inflammation, regulating the ratio of collagen I/III, and improving the vascularization and granulation tissue formation. Thus, AS-loaded hydrogels show huge potential as multifunctional dressings for in vivo hemostasis, sutureless wound closure, and scar-free repair of infected skin wounds.

Biodegradable gelatin/silver nanoparticle composite cryogel with excellent antibacterial and antibiofilm activity and hemostasis for Pseudomonas aeruginosa-infected burn wound healing.

Burn wounds are susceptible to bacterial infections and are usually accompanied by a large amount of exudate, making the treatment of burn wounds a challenge in the clinic. Here, we developed a biodegradable cryogel with high water absorption and good antibacterial and antibiofilm activity based on gelatin (GT) and silver nanoparticles (Ag NPs) to promote burn wound healing. The porous GT/Ag cryogel had a swelling ratio of up to 4000%, effectively absorbing wound exudate and allowing for gas exchange. Moreover, the GT/Ag cryogel had an excellent killing effect on methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PA), which burn wounds are susceptible to, and can effectively remove mature biofilms. In the rat liver defect noncompressible hemorrhage model, GT/Ag cryogels with shape memory performance showed better hemostatic ability than commercial gelatin sponges. Most importantly, the GT/Ag cryogel was more effective than the TegadermTM dressing and GT cryogel in promoting wound contraction, collagen deposition, and angiogenesis and reducing inflammation in a PA-infected burn wound model. In addition, GT/Ag cryogels degraded in the body within 4 weeks, which alleviated the pain of peeling the dressing from the wound. Therefore, GT/Ag cryogels with outstanding antibacterial properties and effective absorption of wound exudates are excellent candidates for wound dressings to promote burn wound repair.

Intra-articular injection of clioquinol ameliorates osteoarthritis in a rabbit model.

Osteoarthritis (OA) is characterized by the degeneration of articular cartilage. Decreased autophagy is tightly associated with chondrocyte death, which contributes to the progression of OA. Thus, pharmacological activation of autophagy may be a promising therapeutic approach for OA. Here, we discovered that clioquinol, an antibiotic, significantly induces autophagy in OA chondrocytes from human tissue and rabbit model. Meanwhile, clioquinol can also augment the expression of extracellular matrix (ECM) components and suppress inflammatory mediators to improve OA microenvironment. Intra-articular injection of clioquinol can greatly prevent or slow down the development of this disease in a trauma-induced rabbit model of osteoarthritis. Such protective effect induced by clioquinol was at least in part explained by decreasing chondrocyte apoptosis and increasing autophagy. This study reveals the therapeutic potential of clioquinol in OA treatment.

Micropatterned conductive elastomer patch based on poly (glycerol sebacate)-graphene for cardiac tissue repair.

Preparing a micropatterned elastomer film with characteristics that can simulate the mechanical properties, anisotropy, and electroactivity of natural myocardial tissues is crucial in cardiac tissue engineering after myocardial infarction (MI). Therefore, in this study, we developed several elastomeric films with a surface micropattern based on poly (glycerol sebacate) (PGS) and graphene (Gr). These films have sufficient mechanical strength (0.6 ± 0.1-3.2 ± 0.08 MPa) to withstand heartbeats, and the micropatterned structure also satisfies the natural myocardium anisotropy in the transverse and vertical. Moreover, Gr makes these films conductive (up to 5.80 × 10-7S m-1), which is necessary for the conduction of electrical signals between cardiomyocytes and the cardiac tissue. Furthermore, they have good cytocompatibility and can promote cell proliferation in H9c2 rat cardiomyocyte cell lines.In vivotest results indicate that these films have good biocompatibility. Notably, a film with 1 wt% Gr content (PGS-Gr1) significantly affects the recovery of myocardial function in rats after MI. This film effectively decreased the infarct size and degree of myocardial fibrosis and reduced collagen deposition. Echocardiographic evaluation showed that after treatment with this film, the left ventricular internal dimension (LVID) in systole and LVID in diastole of rats exhibited a significant downward trend, whereas the fractional shortening and ejection fraction were significantly increased compared with the control group. These data indicate that this electroactive micropatterned anisotropic elastomer film can be applied in cardiac tissue engineering.

Bioprinted living tissue constructs with layer-specific, growth factor-loaded microspheres for improved enthesis healing of a rotator cuff.

Substantial challenges remain in constructing the native tendon-to-bone interface for rotator cuff healing owing to the enthesis tissues' highly organized structural and compositional gradients. Herein, we propose to bioprint living tissue constructs with layer-specific growth factors (GFs) to promote enthesis regeneration by guiding the zonal differentiation of the loaded stem cells in situ. The sustained release of tenogenic, chondrogenic, and osteogenic GFs was achieved via microsphere-based delivery carriers embedded in the bioprinted constructs. Compared to the basal construct without GFs, the layer-specific tissue analogs realized region-specific differentiation of stem cells in vitro. More importantly, bioprinted living tissue constructs with layer-specific GFs rapidly enhanced the enthesis regeneration in a rabbit rotator cuff tear model in terms of biomechanical restoration, collagen deposition, and alignment, showing gradient interface of fibrocartilage structures with aligned collagen fibrils and an ultimate load failure of 154.3 ± 9.5 N resembling those of native enthesis tissues in 12 weeks. This exploration provides a feasible strategy to engineer living tissue constructions with region-specific differentiation potentials for the functional repair of gradient enthesis tissues. STATEMENT OF SIGNIFICANCE: Previous studies that employed acellular layer-specific scaffolds or stem cells for the reconstruction of the rotator cuff faced challenges due to their insufficient capability to rebuild the anisotropic compositional and structural gradients of native enthesis tissues. This manuscript proposed a living tissue construct with layer-specific, GFs-loaded µS, which can direct in situ and region-specific differentiation of the embedded stem cells to tenogenic, chondrogenic, and osteogenic lineages for functional regeneration of the enthesis tissues. This bioprinted living tissue construct with the unique capability to reduce fibrovascular scar tissue formation and simultaneously facilitate enthesis tissue remodeling might provide a promising strategy to repair complex and gradient tissues in the future.

Imidazolium-Based Ionic Liquid-Assisted Preparation of Nano-Spheres Loaded with Bio-Active Peptides to Decrease Inflammation in an Osteoarthritis Model: Ex Vivo Evaluations.

Osteoarthritis is one of the most prevalent chronic diseases. Cartilage inflammation in osteoarthritis results from pain in articular joints. Anti-inflammatory drugs provide relief by hindering the production of pro-inflammatory cytokines and interleukin-6. Targeted delivery of anti-inflammatory drugs is very effective in the treatment of osteoarthritis. This approach reduces the usage of therapeutic drug dosages and unwanted side effects. Here, we fabricated a non-invasive and efficient targeted drug delivery system to reduce persistent inflammation in an osteoarthritis model. Temperature-sensitive hollow dextran/poly(N-isopropyl acrylamide) nanoparticles were synthesized by the destruction of N,N'-bis(acryloyl)cystamine crosslinked cores in imidazolium-based ionic liquids. The copolymerized 2-acrylamido-2-methylpropane sulfonic acid created sulfur functionalities that increase the loading of therapeutic KAFAK peptides. The chemical structure of the polymer nanoparticles was analyzed with UV-Visible, Fourier transform infrared, and X-ray photoelectron spectroscopy. The thermal responsive characteristics of the nanoparticles were determined with dynamic light scattering, scanning electron microscopy, and transmission electron microscopy analyses. Moreover, the synthesized nanoparticles were used as drug carriers to reduce inflammation in an Ex Vivo osteoarthritis model. The KAFAK-loaded hollow dextran/PNIPAM nanoparticles effectively delivered therapeutic peptides in cartilage explants to suppress inflammation. These thermoresponsive nanoparticles could be an effective drug delivery system to deliver anti-inflammatory therapeutic peptides in a highly osteoarthritic environment.

Synergistic enhancement of tendon-to-bone healing via anti-inflammatory and pro-differentiation effects caused by sustained release of Mg2+/curcumin from injectable self-healing hydrogels.

Poor healing response after rotator cuff reconstruction is multifactorial, with the inflammatory microenvironment and deficiency of stem cell differentiation factors at the lesion site being most relevant. However, there is a lack of effective tissue engineering strategies that can simultaneously exert anti-inflammatory and pro-differentiation effects to promote rotator cuff healing. Methods: In this study, we synthesized and characterized a novel active drug delivery vector that successfully overcame the challenge of simultaneous high-efficiency loading and controlled release of Mg2+ and curcumin. The anti-inflammatory and pro-differentiation effects of the composite hydrogel were evaluated in vitro and in vivo. Moreover, healing of the rotator cuff tendon-to-bone interface was studied by histology, immunofluorescence, and biomechanical tests. Results: The composite hydrogel exhibited excellent biocompatibility and injectability, good adhesiveness, and rapid self-healing. The released curcumin showed obvious anti-inflammatory and antioxidation effects, which protected stem cells and tendon matrix. Furthermore, released Mg2+ promoted stem cell aggregation and chondrogenesis. Moreover, biomechanical tests and histological results of a rat rotator cuff tear model at 8 weeks after surgery indicated that the composite hydrogel significantly enhanced tendon-to-bone healing. Conclusions: The composite hydrogel mediated sustained in situ release of curcumin and Mg2+ to effectively promote rotator cuff tendon-to-bone healing via anti-inflammatory and pro-differentiation effects. Therefore, this composite hydrogel offers significant promise for rotator cuff repair.