Oxidized Dextran/Chitosan Hydrogel Engineered with Tetrasulfide-Bridged Silica Nanoparticles for Postsurgical Treatment.

Tumor recurrence and wound microbial infection after tumor excision are serious threats to patients. Thus, the strategy to supply a sufficient and sustained release of cancer drugs and simultaneously engineer antibacterial properties and satisfactory mechanical strength is highly desired for tumor postsurgical treatment. Herein, A novel double-sensitive composite hydrogel embedded with tetrasulfide-bridged mesoporous silica (4S-MSNs) is developed. The incorporation of 4S-MSNs into oxidized dextran/chitosan hydrogel network, not only enhances the mechanical properties of hydrogels, but also can increase the specificity of drug with dual pH/redox sensitivity, thereby allowing more efficient and safer therapy. Besides, 4S-MSNs hydrogel preserves the favorable physicochemical properties of polysaccharide hydrogel, such as high hydrophilicity, satisfactory antibacterial activity, and excellent biocompatibility. Thus, the prepared 4S-MSNs hydrogel can be served as an efficient strategy for postsurgical bacterial infection and inhibition of tumor recurrence.

Prolonged Anesthesia Effects of Locally Administered Ropivacaine via Electrospun Poly(caprolactone) Fibrous Membranes.

Prolonged analgesia is important to safeguard the patient's comfort and safety during and after surgery in clinical practice. To meet the demand for prolonged analgesia, medical professionals often resort to increasing drug frequency, which may lead to poor patient compliance and serious complications due to drug overdose. Therefore, it is of great interest to develop controlled-release drug delivery systems for local anesthetics, enabling slow and controlled drug release to prolong the analgesic effect and minimize systemic toxicity. In this study, we utilized an electrospinning technique to fabricate nonwoven poly(caprolactone) (PCL) fibrous membranes loaded with Ropivacaine and performed proof-of-principle experiments on both in vitro drug release tests and in vivo animal tests, to further prolong the analgesic effect of Ropivacaine and improve postoperative local pain management and chronic pain treatment. Material characterization and in vitro drug release studies confirmed the feasibility of the Ropivacaine-loaded PCL fibrous membranes for sustained release. The drug loading content and drug loading efficiency of Ropivacaine-loaded fibrous membrane are 8.7 ± 0.3 wt% and 96 ± 3 wt%, respectively. Evaluation in an animal model demonstrated prolonged anesthesia effects along with excellent biocompatibility and stability. At 72 h, the cumulative release accounted for approximately 50% of the drug loading content. This study offers novel approaches and strategies for clinical postoperative pain management and chronic pain treatment, while providing new insights and directions for the design of local anesthetic controlled-release delivery systems.

Overcoming the immune suppressive nature of glioblastoma by leveraging the surgical intervention - current status and future perspectives.

Despite relentless efforts to improve outcome, the prognosis of glioblastoma (GBM) remains poor. Standard therapy at first diagnosis consists of maximal safe surgical resection followed by radiochemotherapy, but treatment options at recurrence are scarce and have limited efficacy. Immunotherapy is a broad term that covers several treatment strategies, including immune checkpoint inhibition (ICI). The successes of systemically administered therapeutic monoclonal antibodies that block the Programmed death receptor or ligand (PD-(L)1) and Cytotoxic T-Lymphocyte associated protein (CTLA)-4 immune checkpoints in other cancer types could not be reproduced in glioblastoma. This is considered to be related to the intrinsic low immunogenicity and strong immunosuppressive tumor microenvironment of glioblastoma, in addition to the presence of a blood-glioma and blood-brain barrier that limits many systemically administered therapeutic agents from reaching their target. In this mini-review, we address the specific aspects of immune suppression in glioblastoma and discuss potential strategies that could help to overcome it. The potential advantages of incorporating surgical resection in clinical trials of immunotherapy for glioblastoma, including window-of-opportunity studies, are highlighted. Combination strategies that include surgical resection, as well as local administration of therapeutic agents in the brain are discussed as a potential strategy to achieve an effective immunological response against glioblastoma.

Prospects for the Use of Metal-Based Nanoparticles as Adjuvants for Local Cancer Immunotherapy.

Immunotherapy is among the most effective approaches for treating cancer. One of the key aspects for successful immunotherapy is to achieve a strong and stable antitumor immune response. Modern immune checkpoint therapy demonstrates that cancer can be defeated. However, it also points out the weaknesses of immunotherapy, as not all tumors respond to therapy and the co-administration of different immunomodulators may be severely limited due to their systemic toxicity. Nevertheless, there is an established way through which to increase the immunogenicity of immunotherapy-by the use of adjuvants. These enhance the immune response without inducing such severe adverse effects. One of the most well-known and studied adjuvant strategies to improve immunotherapy efficacy is the use of metal-based compounds, in more modern implementation-metal-based nanoparticles (MNPs), which are exogenous agents that act as danger signals. Adding innate immune activation to the main action of an immunomodulator makes it capable of eliciting a robust anti-cancer immune response. The use of an adjuvant has the peculiarity of a local administration of the drug, which positively affects its safety. In this review, we will consider the use of MNPs as low-toxicity adjuvants for cancer immunotherapy, which could provide an abscopal effect when administered locally.

Optimization strategies of mesenchymal stem cell-based therapy for acute kidney injury.

Considering the high prevalence and the lack of targeted pharmacological management of acute kidney injury (AKI), the search for new therapeutic approaches for it is in urgent demand. Mesenchymal stem cells (MSCs) have been increasingly recognized as a promising candidate for the treatment of AKI. However, clinical translation of MSCs-based therapies is hindered due to the poor retention and survival rates as well as the impaired paracrine ability of MSCs post-delivery. To address these issues, a series of strategies including local administration, three-dimensional culture, and preconditioning have been applied. Owing to the emergence and development of these novel biotechnologies, the effectiveness of MSCs in experimental AKI models is greatly improved. Here, we summarize the different approaches suggested to optimize the efficacy of MSCs therapy, aiming at promoting the therapeutic effects of MSCs on AKI patients.

Self-intensified synergy of a versatile biomimetic nanozyme and doxorubicin on electrospun fibers to inhibit postsurgical tumor recurrence and metastasis.

Tumor-positive resection margins after surgery can result in tumor recurrence and metastasis. Although adjuvant postoperative radiotherapy and chemotherapy have been adopted in clinical practice, they lack efficacy and result in unavoidable side effects. Herein, a self-intensified in-situ therapy approach using electrospun fibers loaded with a biomimetic nanozyme and doxorubicin (DOX) is developed. The fabricated PEG-coated zeolite imidazole framework-67 (PZIF67) is demonstrated as a versatile nanozyme triggering reactions in cancer cells based on endogenous H2O2 and •O2-. The PZIF67-generated •OH induces reactive oxygen species (ROS) overload, implementing chemodynamic therapy (CDT). The O2 produced by PZIF67 inhibits the expression of hypoxia-up-regulated proteins, thereby suppressing tumor progression. PZIF67 also catalyzes the degradation of glutathione, further disturbing the intracellular redox homeostasis and enhancing CDT. Furthermore, the introduced DOX not only kills cancer cells individually, but also replenishes the continuously consumed substrates for PZIF67-catalyzed reactions. The PZIF67-weakened drug resistance strengthens the cytotoxicity of DOX. The combined application of PZIF67 and DOX also suppresses metastasis-associated genes. Both in vitro and in vivo results demonstrate that the self-intensified synergy of PZIF67 and DOX on electrospun fibers efficiently prevents postsurgical tumor recurrence and metastasis, offering a feasible therapeutic regimen for operable malignant tumors.

Progress of research on oral mucosal adhesive agents.

Oral mucosal administration is extensively used to treat systemic diseases and oral mucosal diseases owing to unique oral mucosal structure and convenient administration. However, the special microenvironment of the oral cavity being open, moving, and humid causes oral mucosal drug delivery to face great challenges. To address this dilemma, local adhesive agents have been widely studied for sustained drug delivery and improved bioavailability, showing broad prospects. Recently, the author has performed studies on oral mucosal adhesive agents. In this paper, the progress of research on oral mucosal adhesive materials is reviewed.

A Comparative Study of Mesenchymal Stem Cell-Derived Extracellular Vesicles' Local and Systemic Dose-Dependent Administration in Rat Spinal Cord Injury.

Spinal cord injury (SCI) is a serious neurological condition that causes severe disability. One of the approaches to overcoming the complications of SCI is stem cell-derived extracellular vesicle (EV) therapy. In this research, we performed a comparative evaluation of rat spinal cord post-traumatic regeneration efficacy using different methods of mesenchymal stem cell-derived EV transplantation (local vs. systemic) followed by evaluation of their minimal therapeutic dose. The results suggested that MSC-EV therapy could improve locomotor activity over 60 days after the SCI, showing a dose-dependent effect on the recovery of spinal cord motor pathways. We also established the possibility of maintaining a population of mature oligodendrocytes by MSC-EVs. It was observed that in the spinal cord injury area, intravenous transplantation of MSC-EVs showed more pronounced therapeutic effects compared to the treatment of fibrin matrix-encapsulated MSC-EVs.

Thermosensitive Hydrogels and Advances in Their Application in Disease Therapy.

Thermosensitive hydrogels, having unique sol-gel transition properties, have recently received special research attention. These hydrogels exhibit a phase transition near body temperature. This feature is the key to their applications in human medicine. In addition, hydrogels can quickly gel at the application site with simple temperature stimulation and without additional organic solvents, cross-linking agents, or external equipment, and the loaded drugs can be retained locally to improve the local drug concentration and avoid unexpected toxicity or side effects caused by systemic administration. All of these features have led to thermosensitive hydrogels being some of the most promising and practical drug delivery systems. In this paper, we review thermosensitive hydrogel materials with biomedical application potential, including natural and synthetic materials. We describe their structural characteristics and gelation mechanism and briefly summarize the mechanism of drug release from thermosensitive hydrogels. Our focus in this review was to summarize the application of thermosensitive hydrogels in disease treatment, including the postoperative recurrence of tumors, the delivery of vaccines, the prevention of postoperative adhesions, the treatment of nervous system diseases via nasal brain targeting, wound healing, and osteoarthritis treatment.

Methodological Considerations in Development of UV Imaging for Characterization of Intra-Tumoral Injectables Using cAMP as a Model Substance.

A UV imaging release-testing setup comprising an agarose gel as a model for tumorous tissue was developed. The setup was optimized with respect to agarose concentration (0.5% (w/v)), injection procedure, and temperature control. A repeatable injection protocol was established allowing injection into cavities with well-defined geometries. The effective resolution of the SDi2 UV imaging system is 30-80 µm. The linear range of the imaging system is less than that of typical spectrophotometers. Consequently, non-linear cAMP calibration curves were applied for quantification at 280 nm. The degree of deviation from Beer's law was affected by the background absorbance of the gel matrix. MATLAB scripts provided hitherto missing flexibility with respect to definition and utilization of quantification zones, contour lines facilitating visualization, and automated, continuous data analysis. Various release patterns were observed for an aqueous solution and in situ forming Pluronic F127 hydrogel and PLGA implants containing cAMP as a model for STING ligands. The UV imaging and MATLAB data analysis setup constituted a significant technical development in terms of visualizing behavior for injectable formulations intended for intra-tumoral delivery, and, thereby, a step toward establishment of a bio-predictive in vitro release-testing method.

Topical administration of tranexamic acid in elderly patients undergoing short femoral nailing for intertrochanteric fracture: A randomised controlled trial.

INTRODUCTION: Topical application of tranexamic acid (TXA) has been proposed as an alternative to intravenous administration to reduce perioperative bleeding in orthopaedic surgery. The purpose of this randomised controlled trial was to evaluate the efficacy and safety of 1 g topically applied TXA in patients undergoing fixation of intertrochanteric hip fractures by short femoral nailing. METHODS: A total of 121 patients were enrolled between May 2018 and January 2020. Patients were randomly allocated (1:1) to receive either 10 mL (1 g) of TXA or 10 mL of normal saline (NS) injected through the subfascial drain following wound closure. Total blood loss, total drain output and blood transfusion requirements up to postoperative day 3 were recorded. Rates of thromboembolic complications and mortality up to 90 days postoperatively were also compared. RESULTS: There was no statistically significant difference in total blood loss, total drain output or proportion of patients requiring transfusions. Median total blood loss was 1.088 L (IQR: 0.760-1.795) in the TXA group and 1.078 L (IQR: 0.797-1.722) in the NS group (P = .703). Median total drain output was 60 mL (IQR: 40-140) in the TXA group and 70 mL (IQR: 30-168) in the NS group (P = .696). Blood transfusions were administered in 29 patients (47.5%) in the TXA group and 27 patients (45.0%) in the NS group (P = .782). There was also no difference in frequency of thrombotic complications or mortality within 90 days. There were five thrombotic events in the TXA group and four in the NS group (P = .751). The 90-day mortality rate was 6.6% (4 patients) in the TXA group and 3.3% (2 patients) in the NS group (P = .680). CONCLUSION: A 1 g dose of topically administered TXA did not produce any difference in blood loss, transfusion requirements, thromboembolic complications, or 90-day mortality. Future trials may consider the effect of larger doses in patients undergoing hip fracture fixation surgery.

Evaluation of health managers' opinions about decentralization in health services.

OBJECTIVE: It was aimed to determine the opinions of health-care managers on theimplementation of decentralization in health-care services. METHODS: The research is a cross-sectional and descriptive study.Sample of the study included 261 health managers.Research data were collected from health-care managers between June 8 and July 17, 2020, using face-to-face interviews technic by a questionnaire, in an average of 20-25 minutes. The obtained data were transferred to the computer environment and analyzed with the number, percentage, and Chi-square tests. RESULTS: About 52.5% of the health managers stated that health-care services should be provided by the public, 63.2% of them stated that health-care services should be a form of empowered decentralization, 41.8% of them stated that decentralization could be successful in Turkiye, 62.6% stated that decentralization would provide flexibility in health-care management, 70.3% of them said that it could find solutions to the problems, and 73.3% of them stated that it will improve employee performance whereas 44.9% of them stated that it would negatively affect providing services in integrity, 67.2% of them stated that it would cause regional inequalities, 73.2% of them said that local factors will intervene in health-care services, and 57.9% reported that it would weaken the central power. CONCLUSION: The majority of health-care managers prefer that health-care services are provided by the public health-care service and prefer the empowered decentralization of health-care services. More than half of the health-care managers expressed their positive views such as the fact that decentralization provides flexibility in health-care services, improve the performance, and participation in service along with the negative views such as the fact that decentralization negatively affects the service delivery, causes regional inequalities and intervention of local factors, and weakens the central power.

Is CD19-directed chimeric antigen receptor T cell therapy a smart strategy to combat central nervous system lymphoma?

Primary central nervous system lymphoma (PCNSL) is a rare form and aggressive type of diffuse large B-cell lymphoma (DLBCL) that occurs in both immunocompetent and immunocompromised adults. While adding rituximab to chemotherapeutic regimens resulted in dramatic improvement in both progression-free survival and overall survival in patients with non-central nervous system (CNS) DLBCL, the outcomes of PCNSL are generally poor due to the immune-privileged tumor microenvironment or suboptimal delivery of systemic agents into tumor tissues. Therefore, more effective therapy for PCNSL generally requires systemic therapy with sufficient CNS penetration, including high-dose intravenous methotrexate with rituximab or high-dose chemotherapy followed by autologous stem cell transplantation. However, overall survival is usually inferior in comparison to non-CNS lymphomas, and treatment options are limited for elderly patients or patients with relapsed/refractory disease. Chimeric antigen receptor T (CAR-T) cell therapy has emerged as a cutting-edge cancer therapy, which led to recent FDA approvals for patients with B-cell malignancies and multiple myeloma. Although CAR-T cell therapy in patients with PCNSL demonstrated promising results without significant toxicities in some small cohorts, most cases of PCNSL are excluded from the pivotal CAR-T cell trials due to the concerns of neurotoxicity after CAR-T cell infusion. In this review, we will provide an overview of PCNSL and highlight current approaches, resistance mechanisms, and future perspectives of CAR-T cell therapy in patients with PCNSL.

Based on clinical application research progress of thermosensitive gel in different drug delivery sites / 药学学报

The advantages of local administration are as follow: release drugs directly at the lesion, increase the drug concentration in lesion location and reduce the side effects of systemic administration. Thermosensitive gel is one of typical local administration agents. It exhibits the different physical characteristics with the change of temperature. It is sol-gel at low temperature or storage temperature, while when the temperature rises to the transition temperature or near the body temperature, it is semisolid gel with a certain viscoelasticity, and can recover rapidly. It can enhance the local adhesion, which prolongs the local retention time of drugs. As a result, thermosensitive gel can control and display the release of drugs, which can significantly improve the bioavailability of drugs. This review summarizes the characteristics of thermosensitive gel, thermosensitive materials, and its application in different parts: nasal cavity, eye, vagina, periodontal, skin, tumor and joint cavity, based on clinical needs.

Locally Injectable Hydrogels for Tumor Immunotherapy.

Hydrogel-based local delivery systems provide a good delivery platform for cancer immunotherapy. Injectable hydrogels can directly deliver antitumor drugs to the tumor site to reduce systemic toxicity and achieve low-dose amplification immunotherapy. Therefore, it may overcome the problems of low drug utilization rate and the systemic side effects in cancer immunotherapy through systemic immune drugs, and it provides simple operation and little invasion at the same time. This study aimed to review the research progress of injectable hydrogels in tumor immunotherapy in recent years. Moreover, the local delivery of multiple drugs using injectable hydrogels in tumors is introduced to achieve single immunotherapy, combined chemo-immunotherapy, combined radio-immunotherapy, and photo-immunotherapy. Finally, the application of hydrogels in tumor immunotherapy is summarized, and the challenges and prospects for injectable hydrogels in tumor immunotherapy are proposed.

Updates on Wound Infiltration Use for Postoperative Pain Management: A Narrative Review.

Local anesthetic wound infiltration (WI) provides anesthesia for minor surgical procedures and improves postoperative analgesia as part of multimodal analgesia after general or regional anesthesia. Although pre-incisional block is preferable, in practice WI is usually done at the end of surgery. WI performed as a continuous modality reduces analgesics, prolongs the duration of analgesia, and enhances the patient's mobilization in some cases. WI benefits are documented in open abdominal surgeries (Caesarean section, colorectal surgery, abdominal hysterectomy, herniorrhaphy), laparoscopic cholecystectomy, oncological breast surgeries, laminectomy, hallux valgus surgery, and radical prostatectomy. Surgical site infiltration requires knowledge of anatomy and the pain origin for a procedure, systematic extensive infiltration of local anesthetic in various tissue planes under direct visualization before wound closure or subcutaneously along the incision. Because the incidence of local anesthetic systemic toxicity is 11% after subcutaneous WI, appropriate local anesthetic dosing is crucial. The risk of wound infection is related to the infection incidence after each particular surgery. For WI to fully meet patient and physician expectations, mastery of the technique, patient education, appropriate local anesthetic dosing and management of the surgical wound with "aseptic, non-touch" technique are needed.

Enzyme-instructed hybrid nanogel/nanofiber oligopeptide hydrogel for localized protein delivery.

Enzyme-catalysis self-assembled oligopeptide hydrogel holds great interest in drug delivery, which has merits of biocompatibility, biodegradability and mild gelation conditions. However, its application for protein delivery is greatly limited by inevitable degradation of enzyme on the encapsulated proteins leading to loss of protein activity. Moreover, for the intracellularly acted proteins, cell membrane as a primary barrier hinders the transmembrane delivery of proteins. The internalized proteins also suffer from acidic and enzymatic degradation in endosomes and lysosomes. We herein develop a protease-manipulated hybrid nanogel/nanofiber hydrogel for localized delivery of intracellularly acted proteins. The embedded polymeric nanogels (CytoC/aNGs) preserve activity of cytochrome c (CytoC) that is an intracellular activator for cell apoptosis as a model protein against proteolysis, and do not affect the gelation properties of the protease-catalysis assembled hydrogels. The injectable hydrogel (CytoC/aNGs/Gel) serves as a reservoir to enhance intratumoral retention and realize sustainable release of CytoC/aNGs. The released CytoC/aNGs increase cellular uptake of CytoC and enhance its intracellular delivery to its target site, cytoplasm, resulting in favorable apoptosis-inducing and cytotoxic effects. We show that a single local administration of CytoC/aNGs/Gel efficiently inhibit the tumor growth in the breast tumor mouse model.

Tramas en la construcción de la intersectorialidad para atender la primera infancia / Framework of intersectionality construction for early childhood assistance / Tramas na construção da intersetorialidade para atender a primeira infância

Resumen (analítico) Se presentan los resultados de una investigación cualitativa realizada desde una perspectiva interpretativa-histórica, para comprender la construcción de relaciones intersectoriales en el programa de atención a la primera infancia de Medellín entre el 2004 y el 2014. Se recurrió al análisis documental y a la observación participante en espacios de gestión de políticas públicas y se implementaron entrevistas semiestructuradas a funcionarios gubernamentales y no gubernamentales. La información se analizó desde tres dimensiones interdependientes: ideológica, política y administrativa. Según los resultados, las acciones intersectoriales se ven favorecidas por la adopción del enfoque de derechos, la implementación de instrumentos de política pública y la búsqueda del posicionamiento de los servicios en la comunidad; sin embargo, estos aspectos están atravesados por tensiones derivadas del intento de articular diferentes miradas, relaciones de poder y acciones administrativas.

Abstract (analytical) His paper presents the results of qualitative research carried out from an interpretative-historical perspective, to understand the construction of intersectoral relationships in the program of early childhood care in Medellin between 2004 and 2014. Documentary analysis and participant observation were used in public policy management spaces, and semi-structured interviews with government and non-government officials were implemented. The data was analyzed from three interdependent dimensions: ideological, political, and administrative. According to the results, intersectoral actions are favored by the adoption of the rights approach, the implementation of public policy instruments, and the search for the positioning of services in the community. However, these aspects are traversed by tensions derived from the attempt to articulate different views, power relations, and administrative actions.

Resumo (analítico) Este artigo apresenta os resultados da pesquisa qualitativa realizada desde uma perspectiva interpretativa-histórica, para entender a construção de relações intersetoriais no programa da atenção à primeira infância de Medellín entre o 2004 e o 2014. Recorreu-se à análise documental e à observação participante em espaços de gestão de políticas públicas e implementaram-se entrevistas semiestruturadas a funcionários governamentais e não governamentais. A informação foi analisada desde três dimensões interdependentes: ideológica, política e administrativa. Segundo os resultados, as ações intersetoriais se veem favorecidas pelo uso do enfoque de direitos, a implementação de instrumentos de política pública e a procura do posicionamento dos serviços na comunidade; mesmo assim, estes aspectos estão atravessados por tensões derivadas da tentativa de articular diferentes olhares, relações de poder e ações administrativas.

Local administration of anti-hepatocyte growth factor-neutralizing antibody reverts naturally occurring periodontitis.

OBJECTIVES: Periodontitis is a chronic inflammatory process associated with the loss of tooth-supporting tissue. The imbalance of epithelial-mesenchymal signaling is considered to drive disease progression, and hepatocyte growth factor (HGF) is one of the main mediators of this interaction. The aim of this study was to validate the role of HGF in the pathogenesis of periodontitis and to evaluate the effects of anti-HGF neutralizing antibodies. METHODS: Gingival tissues from cynomolgus monkeys, which naturally develop severe periodontitis, were isolated to establish an in vitro periodontitis model. Periodontitis-affected monkeys were treated by gingival injection of anti-HGF neutralizing antibodies. The therapeutic effects were documented by clinical examination (probing depth and bleeding on probing), histological examination of tissue, and reevaluation of gingival fibroblasts in the in vitro model. RESULTS: Periodontitis-affected monkeys contain periodontitis-associated fibroblasts (PAFs) with a pro-inflammatory phenotype that induced pronounced collagen degradation in vitro. This degradation was effectively inhibited by anti-HGF-neutralizing antibodies. Locally administered anti-HGF antibody to monkey gingiva clinically improved the severity of periodontitis. This was also reflected in the tissue histology with lower inflammatory cell infiltrates in treated gingiva than in non-treated gingiva. Moreover, fibroblasts isolated from anti-HGF-treated gingiva demonstrated reduced collagen degradation capacity. CONCLUSIONS: Our study confirmed the central role of HGF in the pathogenesis of severe periodontitis in relevant in vitro and in vivo models. The positive effect of anti-HGF treatment provides a strong rationale for the use of anti-HGF-neutralizing antibodies for the treatment of human periodontitis.

Local administration of zoledronic acid prevents traumatic osteonecrosis of the femoral head in rat model.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a refractory disease due to its unclear pathomechanism. Neither conservative treatment nor surgical treatment during the early stage of ONFH achieves satisfactory results. Therefore, this study aims to explore the available evidence on the effect of zoledronic acid on early-stage ONFH. METHODS: For groups were established:the Normal group, model group, Normal saline group(NS group) and zoledronic acid-treated group. The blood supply to the femoral head of animals in the model group and zoledronic acid-treated group was interrupted via a surgical procedure, and zoledronic acid was then locally administered to the femoral head. Four weeks after surgery, all the hips were harvested and evaluated by micro-CT and histopathology(H&E staining, TRAP staining, Toluidine blue staining and masson staining). RESULTS: The values of BMD, BS/BV and Tb.Th in the Normal group and zoledronic acid-treated group were significantly higher than those in the model group and NS group (p â€‹< â€‹0.05). The outcome of H&E staining, Toluidine blue staining and masson staining were consistent with that of micro-CT. CONCLUSION: The local administration of zoledronic acid in the femoral head had positive effects on the bone structure of the femoral head in a modified rat model of traumatic ONFH and offered a promising therapeutic strategy during the early stage of ONFH. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This article could provide a choice for treating patients who have osteonecrosis of femora head and can be the basic research for advanced development over this disease.