Hmga1-overexpressing lentivirus protects against osteoporosis by activating the Wnt/ß-catenin pathway in the osteogenic differentiation of BMSCs.

Postmenopausal osteoporosis is associated with bone formation inhibition mediated by the impaired osteogenic differentiation potential of bone marrow mesenchymal stem cells (BMSCs). However, identifying and confirming the essential genes in the osteogenic differentiation of BMSCs and osteoporosis remain challenging. The study aimed at revealing the key gene that regulated osteogenic differentiation of BMSCs and led to osteoporosis, thus exploring its therapeutic effect in osteoporosis. In the present study, six essential genes related to the osteogenic differentiation of BMSCs and osteoporosis were identified, namely, fibrillin 2 (Fbn2), leucine-rich repeat-containing 17 (Lrrc17), heat shock protein b7 (Hspb7), high mobility group AT-hook 1 (Hmga1), nexilin F-actin-binding protein (Nexn), and endothelial cell-specific molecule 1 (Esm1). Furthermore, the in vivo and in vitro experiments showed that Hmga1 expression was increased during the osteogenic differentiation of rat BMSCs, while Hmga1 expression was decreased in the bone tissue of ovariectomized (OVX) rats. Moreover, the expression of osteogenic differentiation-related genes, the activity of alkaline phosphatase (ALP), and the number of mineralized nodules were increased after Hmga1 overexpression, which was partially reversed by a Wnt signaling inhibitor (DKK1). In addition, after injecting Hmga1-overexpressing lentivirus into the bone marrow cavity of OVX rats, the bone loss, and osteogenic differentiation inhibition of BMSCs in OVX rats were partially reversed, while osteoclast differentiation promotion of BMSCs in OVX rats was unaffected. Taken together, the present study confirms that Hmga1 prevents OVX-induced bone loss by the Wnt signaling pathway and reveals that Hmga1 is a potential gene therapeutic target for postmenopausal osteoporosis.

GAPDH-Silence Microsphere via Reprogramming Macrophage Metabolism and eradicating Bacteria for Diabetic infection bone regeneration.

Macrophage metabolism dysregulation, which is exacerbated by persistent stimulation in infectious and inflammatory diseases, such as diabetic infectious bone defects (DIBD), eventually leads to the failure of bone repair. Here, we have developed an injectable, macrophage-modulated GAPDH-Silence drug delivery system. This microsphere comprises chondroitin sulfate methacrylate (CM) and methacrylated gelatin (GM), while the dimethyl fumarate (DMF)-loaded liposome (D-lip) is encapsulated within the microsphere (CM@GM), named D-lip/CM@GM. Triggered by the over-expressed collagenase in DIBD, the microspheres degrade and release the encapsulated D-lip. D-lip could modulate metabolism by inhibiting GAPDH, which suppresses the over-activation of glycolysis, thus preventing the inflammatory response of macrophages in vitro. While beneficial for macrophages, D-lip/CM@GM is harmful to bacteria. GAPDH, while crucial for glycolysis of staphylococcal species (S. aureus), can be effectively countered by D-lip/CM@GM. We are utilizing existing drugs in innovative ways to target central metabolism for effective eradication of bacteria. In the DIBD model, our results confirmed that the D-lip/CM@GM enhanced bacteria clearance and reprogrammed dysregulated metabolism, thereby significantly improving bone regeneration. In conclusion, this GAPDH-Silence microsphere system may provide a viable strategy to promote diabetic infection bone regeneration.

A new dressing system for accelerating wound recovery after primary total knee arthroplasty: a feasibility study.

PURPOSE: Currently, postoperative wound infection and poor healing of total knee arthroplasty have been perplexing both doctors and patients. We hereby innovatively invented a new dressing system to reduce the incidence of postoperative wound complications. METHODS: We enrolled 100 patients who received primary unilateral total knee arthroplasty and then applied the new dressing system. The data collected included the number of dressing changes, postoperative hospital stay, Visual Analogue Scale score (VAS), the Knee Society Score (KSS), the Knee Injury and Osteoarthritis Outcome Score (KOOS), ASEPSIS scores, The Stony Brook Scar Evaluation Scale (SBSES), wound complications, dressing cost, the frequency of shower and satisfaction. Subsequently, a statistical analysis of the data was performed. RESULTS: Our findings demonstrated the average number of postoperative dressing changes was 1.09 ± 0.38, and the average postoperative hospital stay was 3.72 ± 0.98 days. The average cost throughout a treatment cycle was 68.97 ± 12.54 US dollars. Collectively, the results of VAS, KSS, and KOOS revealed that the pain and function of patients were continuously improved. The results of the four indexes of the ASEPSIS score were 0, whereas the SBSES score was 3.58 ± 0.52 and 4.69 ± 0.46 at two weeks and one month after the operation, respectively. We observed no wound complications until one month after the operation. Remarkably, the satisfaction rate of the patients was 91.85 ± 4.99% one month after the operation. CONCLUSION: In this study, we invented a new dressing system for surgical wounds after total knee arthroplasty and further confirmed its clinical feasibility and safety. CHINESE CLINICAL TRIAL REGISTRY: ChiCTR2000033814, Registered 13/ June/2020.

A New Dressing System for Wound in Enhanced-Recovery Total Hip Arthroplasty: A Randomized and Controlled Trial.

BACKGROUND: Currently, there is a paucity of recommendations in regards to dressing selection within the enhanced recovery after surgery protocol. We devised a new dressing system to accelerate the recovery after total hip arthroplasty (THA). We aimed to present our experience with this new dressing system as an adjunct to wound management in THA and to evaluate its performance. METHODS: From September 2020 to August 2021, we prospectively enrolled 124 patients who underwent a primary THA. The patients were randomly assigned to the intervention (the new dressing system group) or the control (the traditional gauze dressing) group. The primary outcome measures of this study were numbers of dressing changes, postoperative lengths of stay, wound scores including the Stony Brook Scar Evaluation Scale and ASEPSIS scores and wound-related complications. The secondary outcomes include satisfaction scores, dressing-related costs, and pain and functional recovery scores. RESULTS: The intervention group numbers of dressing changes and postoperative lengths of stay were significantly less than the control group (P < .001, P < .001). During the one-month follow-up, the Stony Brook Scar Evaluation Scale in the intervention group was significantly better than that in the control group (P < .001). The intervention group satisfaction was significantly higher than that in the control group (P < .001). There were no statistically significant differences between the two groups in terms of dressing-related costs and pain and function scores. CONCLUSION: The new dressing system could significantly reduce the number of dressing changes and postoperative lengths of stay and increase patient satisfaction scores, which can be an ideal adjunct to wound management in enhanced-recovery THA.

Are cementation quality and clinical outcomes affected by the use of tourniquet in primary total knee arthroplasty?

INTRODUCTION: Total knee arthroplasty is used to treat end-stage knee osteoarthritis with great results. Tourniquet use has become popular over the years because of its various benefits, but the literature regarding functional outcomes, pain and rehabilitation and comparison between tourniquet use and improvement cement penetration and overall improve fixation is limited. The authors proposed a hypothesis that cementation quality, and clinical outcomes can be influenced by tourniquet technique. METHODS: Fifty patients were allocated randomly in two groups: (1) tourniquet was inflated throughout all the procedure and (2) only during skin incision and cementation. Radiolucent lines were analyzed by two and independent examiners, using the The Knee Society Roentgenographic Evaluation and Scoring System. The functional scores used were the Oxford knee score and improvement in visual pain scale (VAS). RESULTS: After a mean follow-up period of 2.4 ± 0.2 years, no difference was observed regarding partial use of tourniquet in the cementation quality (p value > 0.05). There was no difference between groups regarding gender, age, knee side, Visual VAS, Oxford Score, total range-of-motion (ROM), knee extension and knee flexion (p value > 0.05). CONCLUSIONS: No difference was attained regarding functional outcomes and cementation quality regarding two different tourniquet protocols.

Ferroptosis-related gene signature associates with immunity and predicts prognosis accurately in patients with osteosarcoma.

Osteosarcoma has been the most common malignant bone tumor in children and adolescents, while the 5-y survival of osteosarcoma patients gained no significant improvement over the past decades. This study aimed to explore the role of ferroptosis-related genes (FRGs) in the development and prognosis of osteosarcoma. The datasets of osteosarcoma patients including RNA sequencing data and clinical information were acquired from the TRGET and Gene Expression Omnibus (GEO) databases. The identification of molecular subgroups with different FRG expression patterns was achieved through nonnegative matrix factorization (NMF) clustering. The prognostic model was constructed using the least absolute shrinkage and selection operator (LASSO) algorithm and multivariate Cox regression analysis. The ESTIMATE algorithm was applied for determining the stromal score, immune score, ESTIMA score, and tumor purity of osteosarcoma patients. Functional analyses including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, Gene Set Enrichment Analysis (GSEA), and Gene Set Variation Analysis (GSVA) were conducted to explore the underlying mechanisms in the development and prognosis of osteosarcoma. Two molecular subgroups with different FRGs expression patterns were identified. The molecular subgroups with higher immune score and more active immune status showed better prognostic survival. On the basis of FRGs, a prognostic model and a nomogram integrating clinical characteristics were constructed and their prediction efficiency for osteosarcoma prognosis were well validated. Gene functional enrichment analysis showed that these differentially expressed FRGs were mainly enriched in immunity-related signaling pathways, indicating that FRGs may affect the development and prognosis of osteosarcoma by regulating the immune microenvironment. The expression profiles of FRGs were closely related to the immunity status and prognostic survival of osteosarcoma patients. The interaction between ferroptosis and immunity in the development of osteosarcoma could provide a new insight into the exploration of molecular mechanisms and targeted therapies of osteosarcoma patients.

Is high flexion total knee arthroplasty a rewarding procedure? An updated meta-analysis of prospective randomized controlled trials.

INTRODUCTION: The aim of this study is to provide an updated meta-analysis comparing the benefits and clinical outcomes between high flexion (HF)-TKA and standard (S)-TKA. MATERIALS AND METHODS: A detailed database analysis was carried out using Web of Science, PubMed, EMBASE, Cochrane Library, MEDLINE and Clinicaltrial.gov, to identify eligible studies. The meta-analysis and sensitivity analysis were performed using Review Manager 5.3 software and STATA 12.0. RESULTS: Twenty-two randomized control trials (RCTs), including 2841 patients and 4268 knees, were eligible for the meta-analysis. The pooled results of subgroup analysis reveal that there was significant difference between HF-TKA and S-TKA in each subgroup in terms of postoperative ROM, with a higher degree of knee flexion for HF-TKA than S-TKA. However, no statistical difference was identified between HF-TKA and S-TKA in other clinical outcomes including various functional scores and complications. CONCLUSIONS: On the basis of this meta-analysis, we can recommended HF-TKA as an alternative choice to S-TKA for patients requiring higher knee flexion in their daily activities.

Lateral augmentation reconstruction system versus modified Brostrom-Gould procedure: A meta-analysis of RCTs.

BACKGROUND: The aim of this study is to compare the clinical efficacy between the ligament augmentation reconstruction system (LARS) and the modified Brostrom-Gould (MBG) operations in the treatment of chronic ankle instability. METHODS: We searched the MEDLINE, EMBASE, PubMed, Web of Science, the Cochrane library, and the Clinicaltrial.gov databases for eligible studies. The Review Manager 5.3 software was applied to compare various postoperative functional scoring, ankle stability and complications between the two groups. RESULTS: Four randomized controlled trials including a total of 209 patients were conducted. No significant difference was found in terms of postoperative FAOS, FAAM, ankle stability and complications between the LARS and MBG group. CONCLUSIONS: The present meta-analysis suggested that there was no clinical superiority for the LARS operation over the MBG operation for patients with chronic ankle instability.

Successful treatment for bilateral femoral neck insufficiency fractures: a rare lesion case report and an updated review of the literature.

BACKGROUND: The incidence of insufficiency fracture (IF) at femoral neck is low, accounting for about 5% of all insufficiency fractures, and IF at bilateral femoral neck is less common with more occurrence in athlete or serviceman. With the aging of populations, more cases of bilateral femoral neck IF have occurred recently, while the standard clinical treatment still remains lacking due to the complexity of these patients. CASE PRESENTATION: A 55-year-old male patient complained pain in his bilateral hip, with no history of trauma, glucocorticoid hormone consumption or radiotherapy, and imaging examination revealed fracture nonunion and shortening in his left femoral neck, and double fracture line on the right femoral neck. The patient received a cementless THA for the left femoral neck fracture and conservative treatment for the right side, followed by Elcatonin injection and oral administration of Carbonate D3 Granules. After 4 months of fellow-up, the patient presented improved functional scorings in bilateral hip joints, with no signs of prothesis infection or loosening. CONCLUSION: We present a rare case of bilateral femoral neck IF in a middle-aged male and the treatment is successful. The timely CT and MRI examinations of bilateral hip joints for patients was necessary for orthopedists to select proper therapeutic regimen. In addition, the choice for therapeutic regimen of bilateral femoral IF should not only be based on the professional judgement of orthopedists, but also on the wishes of patients.

Application of Self-Made Connection Device in Intractable Intramedullary Device.

BACKGROUND: Intramedullary fixation a standard surgical technique for long bone meta/diaphyseal fractures. There were many difficulties in removal of the intractable intramedullary device. The authors reported a new technique to remove the intractable intramedullary nail by using a self-made connecting device. METHODS: The subject underwent removal of the intramedullary nail using a self-made connecting device, the core components of which were a caudal connecting rod and a sliding hammer in the common intramedullary nail removal device, and the auxiliary device was mainly a clinically commonly used Kirschner wire (K-wire; diameter 1.5-2.5 mm). In technical procedure, the key point was the connection between the k-wire and the intramedullary device, according to the specific conditions of the intramedullary device. RESULTS: From 2012 to 2017, a total of 10 cases of intractable intramedullary devices were taken out using this self-made connection device, including 7 cases of tibial intramedullary nails, 1 case of femoral nail, and 1 case of tibial elastic nail. The technique provided satisfactory results, no infection or re-fracture occurred after the. CONCLUSION: The self-made connecting device may provide new technique for more surgeons in the face of intractable intramedullary device.

Effect of patient-specific instrument on lowering threshold for junior physicians to perform total hip arthroplasty on developmental dysplasia of the hip patients.

PURPOSE: To create a patient-specific instrument (PSI) in lowering the surgical experience requirement for junior physicians to perform total hip arthroplasty (THA) on developmental dysplasia of the hip (DDH) patients. METHODS: Combined with rapid prototyping technology, we created a PSI and established DDH hip model in vitro. We enrolled 48 junior physicians and randomly assigned them into two groups. After creation of the PSI, they performed simulated THA surgery on a full-scale hip model with or without PSI on DDH models. The planned prothesis orientation, post-operative prothesis orientation, and surgery time were recorded. RESULTS: The final cup inclination was 42.0 ± 0.8° in PSI group and 37.8 ± 2.0° in control group, while final cup anteversion was 16.0 ± 0.7° in PSI group and 24.7 ± 3.5° in control group. The △inclination in PSI group was smaller than that in control group (4.2 ± 0.5° vs 9.5 ± 1.4°, P < 0.01), so does △inclination (2.9 ± 0.4° in PSI group vs 15.2 ± 2.5° in control group, P < 0.01). The outlier percent was 8.3% in PSI group and 70.8% in control group (P < 0.01). At the same time, the PSI group did not prolong the operation time (P = 0.551). CONCLUSION: The PSI can greatly increase the accuracy of placing the cup orientation and lower the threshold for junior physicians to perform THA on DDH patients. It could be a training tool for them to increase their THA surgical skills.

Real-time computerised tomography assisted porous tantalum implant in ARCO stage I-II non-traumatic osteonecrosis of the femoral head: minimum five-year follow up.

PURPOSES: This study was established to investigate the medium-term clinical effect of real-time CT assisted porous tantalum implant for the treatment of ARCO stage I-II non-traumatic osteonecrosis of the femoral head (ONFH). METHODS: This study comprised 24 ONFH patients (29 hips) who were treated with intra-operative real-time CT accurate rapid positioning assisted drilling decompression, lesion removal and porous tantalum implant. Harris score, VAS score and imaging in pre-operation and follow-up period were recorded. RESULTS: The average operative time and intra-operative blood loss were 72.6 min and 158.8 ml, respectively. The mean follow-up was 5.4 years. No femoral head penetrating, wound infection, and death occurred. Harris and VAS score improved significantly (73.78 vs. 88.11; 7.13 vs. 2.66) at last follow-up (P < 0.05). The functional improvement and pain relief rate was 100% at six months after operation. The effective rate was 86.21% at 12 months after operation and last follow-up. Five pre-operative ARCO stage I hips had no radiographic progress. Meanwhile, four among the 24 ARCO stage II hips progressed into stage III between eight and 12 months after surgery, among which two progressed into stage IV and two remained in stage III at the last follow-up. The average value of Kerboul combined necrotic angle was 263.24°. There was no progress in Kerboul combined necrotic angle among the grades 2 and 3 patients. However, among the six cases at grade 4, four cases with post-operative progress, two patients converted to THA. CONCLUSIONS: Our technique is safety and effective in the treatment of ARCO stage I-II non-traumatic ONFH.

Prognosis of Advanced Tenosynovial Giant Cell Tumor of the Knee Diagnosed During Total Knee Arthroplasty.

BACKGROUND: Tenosynovial giant cell tumor (TGCT) is a relatively rare disease often misdiagnosed as osteoarthritis. Synovectomy or arthroplasty is the recommended treatment option, but recurrence is common after surgery. This study aimed to determine the prognosis of patients with advanced TGCT that was diagnosed incidentally during total knee arthroplasty (TKA) for osteoarthritis and treated by synovectomy. METHODS: From January 2008 to July 2011, TGCT was diagnosed incidentally in 10 patients (a total of 11 individual knees) undergoing posterior-stabilized TKA for an initial diagnosis of osteoarthritis. TGCT was confirmed by histopathology of biopsy specimens. Partial synovectomy was performed for localized-type TGCT (3 knees, 3 patients) and total synovectomy for diffuse-type TGCT (8 knees, 7 patients). RESULTS: All patients were female with a mean age of 61.7 ± 6.6 (range 50-70) years. No postoperative infection, nerve injury, or deep venous thrombosis occurred. All patients were followed up for a mean period of 60.9 ± 6.6 (39-83) months, and no recurrence of TGCT occurred. X-ray imaging showed no apparent radiolucent lines around the prosthesis, and no prosthetic loosening, subsidence, or osteolysis. The joints were stable, with a significantly improved range of motion following surgery (109.5° ± 8.8° vs 80.5° ± 16.8°, P < .01). The Knee Society scores for knee joint (90.0 ± 4.1 vs 40.5 ± 8.1) and knee function (81.8 ± 7.5 vs 35.0 ± 13.8) were both significantly improved after surgery (P < .01). CONCLUSION: Inactive TGCT could not be diagnosed preoperatively. TKA combined with synovectomy is effective in the treatment of advanced TGCT with degenerative lesions.

Magnetic Seeding of SPIO-BMSCs Into a Biphasic Scaffold Can Promote Tendon-Bone Healing After Rotator Cuff Repair.

BACKGROUND: The tendon-bone interface (TBI) in the rotator cuff has a poor intrinsic capacity for healing, which increases the risk of retear after rotator cuff repair (RCR). However, facilitating regeneration of the TBI still remains a great clinical challenge. Herein, the authors established a novel strategy based on magnetic seeding to enhance the TBI regeneration. HYPOTHESIS: Magnetic seeding bone marrow mesenchymal stem cells labeled with superparamagnetic iron oxide (SPIO-BMSCs) into a biphasic scaffold can promote tendon-bone healing after RCR. STUDY DESIGN: Controlled laboratory study. METHODS: BMSCs were labeled with SPIOs. Prussian blue staining, CCK-8 tests, Western blot, and quantitative reverse transcription polymerase chain reaction (PCR) were used to determine the optimal effect concentration of SPIOs on cell bioactivities and abilities. Then SPIO-BMSCs were magnetically seeded into a biphasic scaffold under a magnetic field. The seeding efficacy was assessed by a scanning electron microscope, and the potential mechanism in chondrogenic differentiation after seeding SPIO-BMSCs into the scaffold was evaluated by Western blot and PCR. Furthermore, the effect of SPIO-BMSC/biphasic scaffold on tendon-bone healing after RCR using a rat model was examined using histological analysis, enzyme-linked immunosorbent assay, and biomechanical evaluation. RESULTS: BMSCs labeled with 100 µg/mL SPIO had no effect on cell bioactivities and the ability of chondrogenic differentiation. SPIO-BMSCs were magnetically seeded into a biphasic scaffold, which offered a high seeding efficacy to enhance chondrogenic differentiation of SPIO-BMSCs via the CDR1as/miR-7/FGF2 pathway for TBI formation in vitro. Furthermore, in vivo application of the biphasic scaffold with magnetically seeded SPIO-BMSCs showed their regenerative potential, indicating that they could significantly accelerate and promote TBI healing with superior biomechanical properties after RCR in a rat rotator cuff tear model. CONCLUSION: Magnetically seeding SPIO-BMSCs into a biphasic scaffold enhanced seeding efficacy to promote cell distribution and condensation. This construct enhanced the chondrogenesis process via the CDR1as/miR-7/FGF2 pathway and further promoted tendon-bone healing after RCR in a rat rotator cuff tear model. CLINICAL RELEVANCE: This study provides an alternative strategy for improving TBI healing after RCR.

Carbomer Hydrogel Composed of Cu2O and Hematoporphyrin Monomethyl Ether Promotes the Healing of Infected Wounds.

Infectious wounds pose a significant challenge in the field of wound healing primarily due to persistent inflammation and the emergence of antibiotic-resistant bacteria. To combat these issues, the development of an effective wound dressing that can prevent infection and promote healing is of the utmost importance. Photodynamic therapy (PDT) has emerged as a promising noninvasive treatment strategy for tackling antibiotic-resistant bacteria. A biodegradable photosensitizer called hematoporphyrin monomethyl ether (HMME) has shown potential in generating reactive oxygen species (ROS) upon laser activation to combat bacteria. However, the insolubility of HMME limits its antibacterial efficacy and its ability to facilitate skin healing. To overcome these limitations, we have synthesized a compound hydrogel by combining carbomer, HMME, and Cu2O nanoparticles. This compound hydrogel exhibits enhanced antimicrobial ability and excellent biocompatibility and promotes angiogenesis, which is crucial for the healing of skin defects. By integrating the benefits of HMME, Cu2O nanoparticles, and the gel-forming properties of carbomer, this compound hydrogel shows great potential as an effective wound dressing material. In summary, the compound hydrogel developed in this study offers a promising solution for infectious wounds by addressing the challenges of infection prevention and promoting skin healing. This innovative approach utilizing PDT and the unique properties of the compound hydrogel could significantly improve the outcomes of wound healing in clinical settings.

Precision pore structure optimization of additive manufacturing porous tantalum scaffolds for bone regeneration: A proof-of-concept study.

Currently, the treatment of bone defects in arthroplasty is a challenge in clinical practice. Nonetheless, commercially available orthopaedic scaffolds have shown limited therapeutic effects for large bone defects, especially for massiveand irregular defects. Additively manufactured porous tantalum, in particular, has emerged as a promising material for such scaffolds and is widely used in orthopaedics for its exceptional biocompatibility, osteoinduction, and mechanical properties. Porous tantalum has also exhibited unique advantages in personalised rapid manufacturing, which allows for the creation of customised scaffolds with complex geometric shapes for clinical applications at a low cost and high efficiency. However, studies on the effect of the pore structure of additively manufactured porous tantalum on bone regeneration have been rare. In this study, our group designed and fabricated a batch of precision porous tantalum scaffolds via laser powder bed fusion (LPBF) with pore sizes of 250 µm (Ta 250), 450 µm (Ta 450), 650 µm (Ta 650), and 850 µm (Ta 850). We then performed a series of in vitro experiments and observed that all four groups showed good biocompatibility. In particular, Ta 450 demonstrated the best osteogenic performance. Afterwards, our team used a rat bone defect model to determine the in vivo osteogenic effects. Based on micro-computed tomography and histology, we identified that Ta 450 exhibited the best bone ingrowth performance. Subsequently, sheep femur and hip defect models were used to further confirm the osteogenic effects of Ta 450 scaffolds. Finally, we verified the aforementioned in vitro and in vivo results via clinical application (seven patients waiting for revision total hip arthroplasty) of the Ta 450 scaffold. The clinical results confirmed that Ta 450 had satisfactory clinical outcomes up to the 12-month follow-up. In summary, our findings indicate that 450 µm is the suitable pore size for porous tantalum scaffolds. This study may provide a new therapeutic strategy for the treatment of massive, irreparable, and protracted bone defects in arthroplasty.

Macrophage metabolic reprogramming-based diabetic infected bone defect/bone reconstruction though multi-function silk hydrogel with exosome release.

Diabetic infected bone defects (DIBD) with abnormal immune metabolism are prone to the hard-to-treat bacterial infections and delayed bone regeneration, which present significant challenges in clinic. Control of immune metabolism is believed to be important in regulating fundamental immunological processes. Here, we developed a macrophage metabolic reprogramming hydrogel composed of modified silk fibroin (Silk-6) and poly-l-lysine (ε-PL) and further integrated with M2 Macrophage-derived Exo (M2-Exo), named Silk-6/ε-PL@Exo. This degradable hydrogel showed a broad-spectrum antibacterial performance against both Gram-positive and -negative bacteria. More importantly, the release of M2-Exo from Silk-6/ε-PL@Exo could target M1 macrophages, modulating the activity of the key enzyme hexokinase II (HK2) to control the inflammation-related NF-κB pathway, alleviate lactate accumulation, and inhibit glycolysis to normalize the cycle, thereby promoting M1-to-M2 balance. Using a rat model of DIBD, Silk-6/ε-PL@Exo hydrogel promoted infection control, balanced immune responses and accelerated the bone defect healing. Overall, this study demonstrates that this Silk-6/ε-PL @Exo is a promising filler biomaterial with multi-function to treat DIBD and emphasizes the importance of metabolic reprogramming in bone regeneration.

Current Advances and Applications of Tantalum Element in Infected Bone Defects.

Infected bone defects (IBDs) cause significant economic and psychological burdens, posing a huge challenge to clinical orthopedic surgeons. Traditional approaches for managing IBDs possess inevitable shortcomings; therefore, it is necessary to develop new functionalized scaffolds. Tantalum (Ta) has been widely used in load-bearing orthopedic implants due to its good biocompatibility and corrosion resistance. However, undecorated Ta could only structurally repair common bone defects, which failed to meet the clinical needs of bacteriostasis for IBDs. Researchers have made great efforts to functionalize Ta scaffolds to enhance their antibacterial activity through various methods, including surface coating, alloying, and micro- and nanostructure modifications. Additionally, several studies have successfully utilized Ta to modify orthopedic scaffolds for enhanced antibacterial function. These studies remarkably extended the application range of Ta. Therefore, this review systematically outlines the advances in the fundamental and clinical application of Ta in the treatment of IBDs, focusing on the antibacterial properties of Ta, its functionalization for bacteriostasis, and its applications in the modification of orthopedic scaffolds. This study provides researchers with an overview of the application of Ta in the treatment of IBDs.

Nano artificial periosteum PCL/Ta/ZnO accelerates repair of periosteum via antibacterial, promoting vascularization and osteogenesis.

The periosteum plays a critical role in bone development, shaping, remodeling, and fracture healing due to its abundance of osteoprogenitor cells, osteoblasts, and capillary network. However, the role of periosteum in bone injury healing has been underestimated, thus there is an urgent need to develop a multifunctional artificial periosteum that mimics the natural one. To tackle this issue, electrospinning technology was employed to fabricate an artificial periosteum composed of Poly-ε-caprolactone (PCL) doped with tantalum (Ta) and zinc oxide (ZnO) nanoparticles to enhance its antibacterial, osteogenic, and angiogenic properties. The in vitro cell experiments have demonstrated that the PCL/Ta/ZnO artificial periosteum exhibits excellent biocompatibility and can effectively facilitate osteogenic differentiation of BMSCs as well as angiogenic differentiation of EPCs. Antibacterial experiments have demonstrated the excellent bactericidal effects of PCL/Ta/ZnO artificial periosteum against both S. aureus and E. coli. The subcutaneous infection and critical-sized skull bone defect models have validated its in vivo properties of antibacterial activity, promotion of osteogenesis, and angiogenic potential. The PCL/Ta/ZnO artificial periosteum demonstrates remarkable efficacy in infection control and favorable immunomodulation, thereby achieving rapid vascularized bone repair. In conclusion, the utilization of PCL/Ta/ZnO tissue-engineered periosteum has been demonstrated to exhibit antibacterial properties, pro-vascularization effects, and promotion of osteogenesis at the site of bone defects. This promising approach could potentially offer effective treatment for bone defects.

Cartilage fragments combined with BMSCs-Derived exosomes can promote tendon-bone healing after ACL reconstruction.

Anterior cruciate ligament reconstruction (ACLR) often fails due to the inability of tendon-bone integration to regenerate normal tissues and formation of fibrous scar tissues in the tendon-bone interface. Cartilage fragments and exosomes derived from bone mesenchymal stromal cells (BMSCs-Exos) can enhance enthesis healing. Nevertheless, the effects on the tendon-bone healing of ACLR remain unknown. This study found that BMSCs-Exos can promote the proliferation of chondrocytes in cartilage fragments, and activated the expression of chondro-related genes SOX9 and Aggrecan. The optimal effect concentration was 1012 events/uL. Besides, BMSCs-Exos could significantly upregulated the expression of BMP7 and Smad5 in cartilage fragments, and further enhanced the expression of chondrogenic genes. Moreover, this study established a rat model of ACLR and implanted the BMSCs-Exos/cartilage fragment complex into the femoral bone tunnel. Results demonstrated that the mean diameters of the femoral bone tunnels were significantly smaller in the BE-CF group than those in the CF group (p = 0.038) and control group (p = 0.007) at 8 weeks after surgery. Besides, more new bone formation was observed in the femoral tunnels in the BE-CF group, as demonstrated by a larger BV/TV ratio based on the reconstructed CT scans. Histological results also revealed the regeneration of tendon-bone structures, especially fibrocartilage. Thus, these findings provide a promising result that BMSCs-Exos/cartilage fragment complex can prevent the enlargement of bone tunnel and promote tendon-bone healing after ACLR, which may have resulted from the regulation of the BMP7/Smad5 signaling axis.