In Situ Sustained Macrophage-Targeted Nanomicelle-Hydrogel Microspheres for Inhibiting Osteoarthritis.

There are still challenges in applying drug nanocarriers for in situ sustained macrophage targeting and regulation, due to the rapid clearance of nanocarriers and burst drug release in vivo. Herein, a nanomicelle-hydrogel microsphere, characterized by its macrophage-targeted nanosized secondary structure that allows it to accurately bind to M1 macrophages through active endocytosis, is employed for in situ sustained macrophage targeting and regulation, and addresses the insufficient osteoarthritis therapeutic efficacy caused by rapid clearance of drug nanocarriers. The 3-dimensional structure of a microsphere can prevent the rapid escape and clearance of a nanomicelle, thus keeping it in joints, while the ligand-guided secondary structure can carry drugs to accurately target and enter M1 macrophages, and release drugs via the transition from hydrophobicity to hydrophilicity of nanomicelles under inflammatory stimulation inside the macrophages. The experiments show that the nanomicelle-hydrogel microsphere can in situ sustainably target and regulate M1 macrophages for more than 14 days in joints, and attenuate local "cytokine storm" by continuous M1 macrophage apoptosis promotion and polarization inhibition. This micro/nano-hydrogel system shows excellent ability to sustainably target and regulate macrophage, realizes the improvement of drug utilization and efficacy inside the macrophage, and thereby can be a potential platform for treating macrophage-related diseases.

Living and Injectable Porous Hydrogel Microsphere with Paracrine Activity for Cartilage Regeneration.

Paracrine is an important mechanism in mesenchymal stem cells (MSCs) that promotes tissue regeneration. However, anoikis is attributed to unsuitable adhesion microenvironment hindered this paracrine effect. In this study, a living and injectable porous hydrogel microsphere with long-term paracrine activity is constructed via the freeze-drying microfluidic technology and the incorporation of platelet-derived growth factor-BB (PDGF-BB) and exogenous MSCs. Benefiting from the porous structure and superior mechanical property of methacrylate gelatin (GelMA) hydrogel microspheres (GMs), exogenous stem cells are able to adhere and proliferate on GMs, thereby facilitating cell-to-extracellular matrix (ECM) and cell-to-cell interactions and enhancing paracrine effect. Furthermore, the sustained release of PDGF-BB can recruit endogenous MSCs to prolong the paracrine activity of the living GMs. In vitro and in vivo experiments validated that the living GMs exhibit superior secretion properties and anti-inflammatory efficacy and can attenuate osteoarthritis (OA) progression by favoring the adherent microenvironment and utilizing the synergistic effect of exogenous and endogenous MSCs. Overall, a living injectable porous hydrogel microsphere that can enhance the paracrine activity of stem cells is fabricated and anticipated to hold the potential of future clinical translation in OA and other diseases.

Injectable Double Positively Charged Hydrogel Microspheres for Targeting-Penetration-Phagocytosis.

The localization and accumulation of drugs in the body determine their therapeutic effects; however, the specific microstructure of damaged tissues hinders drug delivery. Currently, there is a shortage of effective drug carriers to breach these barriers and achieve efficient tissue and cellular delivery of drugs. In this study, an injectable double positively charged functional hydrogel microsphere with "targeting cartilage extracellular matrix", "cartilage penetration", and "cellular phagocytosis" is designed for matching the structural characteristics of joints, addressing the difficulties of drug delivery in joints. The microspheres could be adsorbed on the negatively charged cartilage surface because of their positively charged poly-lysine surface. Furthermore, the internally loaded positively charged polyamidoamine contained kartogenin, which helped further the penetration of the cartilage under the guidance of electrical charge. The microspheres could release kartogenin for more than 21 days. In in vivo experiments, the microspheres effectively improve the efficiency of drug delivery, inhibit the degradation of cartilage matrix and subchondral bone, and delay the development of osteoarthritis. As a double positively charged drug delivery system, the versatile microsphere has great potential for treating osteoarthritis and other diseases.

MDH1 and MDH2 Promote Cell Viability of Primary AT2 Cells by Increasing Glucose Uptake.

Background: Acute lung injury (ALI) is a clinical disease with high morbidity and mortality, with limited treatment means. For primary alveolar epithelial type II (AT2) cells, glycolysis is an essential bioenergetic process. However, the significance of AT2 cell glycolysis in sepsis ALI remains unknown. Methods and Results: In the current study, based on microarray analysis, real-time quantitative PCR, and Western blotting, we found that the hsa00020: citrate cycle pathway was inactivated, specifically its downstream gene: malate dehydrogenase 1 (MDH1) and MDH2 in ALI. In this context, lipopolysaccharides (LPS) were used to construct the septic-ALI mouse model and the biological function of MDH1 and MDH2 in primary alveolar epithelial type II (AT2) cells was explored. Through CCK-8, EdU, transwell, and apoptosis assays, we found that MDH1 and MDH2 promoted the cell vitality of AT2 cells, which relied on MDH1 and MDH2 to promote the glucose intake of AT2 cells. Conclusion: Overall, these findings suggest that targeting MDH1/MDH2-mediated AT2 cell glycolysis may be a potential strategy for ALI patients.

Effect of α-tocopherol in alleviating the lipopolysaccharide-induced acute lung injury via inhibiting nuclear factor kappa-B signaling pathways.

Acute respiratory distress syndrome (ARDS) leads to the acute lung injury (ALI), a form of diffused alveolars injury, accompanied by severe inflammation and oxidative damage of alveolar epithelial cells. α-Tocopherol (α-TOH), one of the eight isoforms of vitamin E, is a natural antioxidant-free radical. We aimed to understand the effect of α-TOH and mechanism involved in inducing the ALI. Lipopolysaccharide (LPS) is injected into the trachea of mice to generate ALI mouse models. α-TOH was used to administrate the mice intragastrically to detect the expression of inflammatory factors and antioxidant molecules by enzyme linked immunosorbent assay, hematoxylin-eosin staining and immunohistochemical staining. Mouse alveolar epithelial cell line (MLE-12 cells) was used to determine the effect of α-TOH on alveolar epithelial cells. Inflammatory factors such as, interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α shows significant increase in the lung tissues of the mice induced by LPS and reduction in the expressions of superoxide dismutase (SOD)1/2 and glutathione peroxidase (GSH-Px). After treatment with α-TOH, the inflammation and oxidative stress levels shows substantial reduction in the lung tissues of the mice. Moreover, α-TOH also increases the proliferation ability of MLE-12 cells in vitro and reduces apoptosis level. In addition, α-TOH reduces p65 phosphorylation and nuclear translocation in alveolar epithelial cells in vivo and in vitro, thus, inhibiting the activity of the nuclear factor kappa-B (NF-κB) signaling pathway. α-TOH reduces the inflammation and oxidative stress of lung tissue by inhibiting the NF-κB signaling pathway, thereby alleviating the LPS-induced ALI.

Isoorientin suppresses sepsis-induced acute lung injury in mice by activating an EPCR-dependent JAK2/STAT3 pathway.

Sepsis is a systemic inflammatory syndrome, and acute lung injury (ALI) is one of the most common fatal complications of sepsis. Isoorientin (ISO) exerts a momentous role in the regulation of inflammation. However, whether ISO has a protective effect on sepsis-induced ALI remains unknown. This research aimed to elucidate the function of ISO on sepsis-induced ALI and its mechanism. In this study, the sepsis-induced ALI was established in the male C57BL/6 J mice. Functionally, ISO reduced the total protein concentration in BALF, lung wet/dry ratio and the numbers of neutrophils and macrophages in BALF as well as ameliorated lung injury. Besides, ISO treatment decreased the cytokine expressions and oxidative stress, and repressed the adhesion and migration of inflammatory cells induced by CLP. Mechanistically, ISO reduced the shedding of EPCR in the endothelial cell membrane; ISO treatment activated the JAK2/STAT3 signaling pathway through EPCR and the JAK2/STAT3 pathway inhibitors repressed the anti-inflammatory and antioxidant effects of ISO. In general, ISO suppressed sepsis-induced ALI in mice by activating an EPCR-dependent JAK2/STAT3 pathway.

Fullerol-hydrogel microfluidic spheres for in situ redox regulation of stem cell fate and refractory bone healing.

The balance of redox homeostasis is key to stem cell maintenance and differentiation. However, this balance is disrupted by the overproduced reactive oxygen species (ROS) in pathological conditions, which seriously impair the therapeutic efficacy of stem cells. In the present study, highly dispersed fullerol nanocrystals with enhanced bioreactivity were incorporated into hydrogel microspheres using one-step innovative microfluidic technology to construct fullerol-hydrogel microfluidic spheres (FMSs) for in situ regulating the redox homeostasis of stem cells and promoting refractory bone healing. It was demonstrated that FMSs exhibited excellent antioxidant activity to quench both intracellular and extracellular ROS, sparing stem cells from oxidative stress damage. Furthermore, these could effectively promote the osteogenic differentiation of stem cells with the activation of FoxO1 signaling, indicating the intrinsically osteogenic property of FMSs. By injecting the stem cells-laden FMSs into rat calvarial defects, the formation of new bone was remarkably reinforced, which is a positive synergic effect from modulating the ROS microenvironment and enhancing the osteogenesis of stem cells. Collectively, the antioxidative FMSs, as injectable stem cell carriers, hold enormous promise for refractory bone healing, which can also be expanded to deliver a variety of other cells, targeting diseases that require in situ redox regulation.

Biomimetic injectable hydrogel microspheres with enhanced lubrication and controllable drug release for the treatment of osteoarthritis.

The occurrence of osteoarthritis (OA) is highly associated with the reduced lubrication property of the joint, where a progressive and irreversible damage of the articular cartilage and consecutive inflammatory response dominate the mechanism. In this study, bioinspired by the super-lubrication property of cartilage and catecholamine chemistry of mussel, we successfully developed injectable hydrogel microspheres with enhanced lubrication and controllable drug release for OA treatment. Particularly, the lubricating microspheres (GelMA@DMA-MPC) were fabricated by dip coating a self-adhesive polymer (DMA-MPC, synthesized by free radical copolymerization) on superficial surface of photo-crosslinked methacrylate gelatin hydrogel microspheres (GelMA, prepared via microfluidic technology), and encapsulated with an anti-inflammatory drug of diclofenac sodium (DS) to achieve the dual-functional performance. The tribological test and drug release test showed the enhanced lubrication and sustained drug release of the GelMA@DMA-MPC microspheres. In addition, the functionalized microspheres were intra-articularly injected into the rat knee joint with an OA model, and the biological tests including qRT-PCR, immunofluorescence staining assay, X-ray radiography and histological staining assay all revealed that the biocompatible microspheres provided significant therapeutic effect against the development of OA. In summary, the injectable hydrogel microspheres developed herein greatly improved lubrication and achieved sustained local drug release, therefore representing a facile and promising technique for the treatment of OA.

Structural and biological investigation of chitosan/hyaluronic acid with silanized-hydroxypropyl methylcellulose as an injectable reinforced interpenetrating network hydrogel for cartilage tissue engineering.

Cartilage damage continues to pose a threat to humans, but no treatment is currently available to fully restore cartilage function. In this study, a new class of composite hydrogels derived from water-soluble chitosan (CS)/hyaluronic acid (HA) and silanized-hydroxypropyl methylcellulose (Si-HPMC) (CS/HA/Si-HPMC) has been synthesized and tested as injectable hydrogels for cartilage tissue engineering when combined without the addition of a chemical crosslinking agent. Mechanical studies of CS/HA and CS/HA/Si-HPMC hydrogels showed that as Si-HPMC content increased, swelling rate and rheological properties were higher, compressive strength decreased and degradation was faster. Our results demonstrate that the CS and HA-based hydrogel scaffolds, especially the ones with 3.0% (w/v) Si-HPMC and 2.5/4.0% (w/v) CS/HA, have suitable physical performance and bioactive properties, thus provide a potential opportunity to be used for cartilage tissue engineering. In vitro studies of CS/HA and CS/HA/Si-HPMC hydrogels encapsulated in chondrocytes have shown that the proper amount of Si-HPMC increases the proliferation and deposition of the cartilage extracellular matrix. The regeneration rate of the CS/HA/Si-HPMC (3%) hydrogel reached about 79.5% at 21 days for long retention periods, indicating relatively good in vivo bone regeneration. These CS/HA/Si-HPMC hydrogels are promising candidates for tissue compatibility injectable scaffolds. The data provide proof of the principle that the resulting hydrogel has an excellent ability to repair joint cartilage using a tissue-engineered approach.RESEARCH HIGHLIGHTSAn injectable hydrogel based on CS/HA/Si-HPMC composites was developed.The CS/HA/Si-HPMC hydrogel displays the tunable rheological with mechanical properties.The CS/HA/Si-HPMC hydrogel is highly porous with high swelling and degradation ratio.Increasing concentration of Si-HPMC promote an organized network in CS/HA/Si-HPMC hydrogels.Injectable CS/HA/Si-HPMC hydrogels have a high potential for cartilage tissue engineering.

Ball-Bearing-Inspired Polyampholyte-Modified Microspheres as Bio-Lubricants Attenuate Osteoarthritis.

Osteoarthritis, a lubrication dysfunction related disorder in joint, is characterized by articular cartilage degradation and joint capsule inflammation. Enhancing joint lubrication, combined with anti-inflammatory therapy, is considered as an effective strategy for osteoarthritis treatment. Herein, based on the ball-bearing-inspired superlubricity and the mussel-inspired adhesion, a superlubricated microsphere, i.e., poly (dopamine methacrylamide-to-sulfobetaine methacrylate)-grafted microfluidic gelatin methacrylate sphere (MGS@DMA-SBMA), is developed by fabricating a monodisperse, size-uniform microsphere using the microfluidic technology, and then a spontaneously modified microsphere with DMA-SBMA copolymer by a one-step biomimetic grafting approach. The microspheres are endowed with enhanced lubrication due to the tenacious hydration layer formed around the charged headgroups (-N+ (CH3 )2 - and -SO3- ) of the grafted poly sulfobetaine methacrylate (pSBMA), and simultaneously are capable of efficient drug loading and release capability due to their porous structure. Importantly, the grafting of pSBMA enables the microspheres with preferable properties (i.e., enhanced lubrication, reduced degradation, and sustained drug release) that are highly desirable for intraarticular treatment of osteoarthritis. In addition, when loaded with diclofenac sodium, the superlubricated microspheres with excellent biocompatibility can inhibit the tumor necrosis factor α (TNF-α)-induced chondrocyte degradation in vitro, and further exert a therapeutic effect toward osteoarthritis in vivo.

Thermo-Sensitive Dual-Functional Nanospheres with Enhanced Lubrication and Drug Delivery for the Treatment of Osteoarthritis.

Osteoarthritis is a typical degenerative joint disease related to a lubrication deficiency of articular cartilage, which is characterized by increased friction at the joint surface and severe inflammation of the joint capsule. Consequently, therapies combining lubrication restoration and drug intervention are regarded as a promising strategy for the treatment of osteoarthritis. In the present study, thermo-sensitive dual-functional nanospheres, poly[N-isopropylacrylamide-2-methacryloyloxyethyl phosphorylcholine] (PNIPAM-PMPC), are developed through emulsion polymerization. The PNIPAM-PMPC nanospheres could enhance lubrication based on the hydration lubrication mechanism by forming a tenacious hydration layer surrounding the zwitterionic headgroups, and achieve local drug delivery by encapsulating the anti-inflammatory drug diclofenac sodium. The lubrication and drug release tests showed improved lubrication and thermo-sensitive drug release of the nanospheres. The in vitro test using cytokines-treated chondrocytes indicated that the PNIPAM-PMPC nanospheres were biocompatible and upregulated anabolic genes and simultaneously downregulated catabolic genes of the articular cartilage. In summary, the developed PNIPAM-PMPC nanospheres, with the property of enhanced lubrication and local drug delivery, can be an effective nanomedicine for the treatment of osteoarthritis.

Bioinspired Hyaluronic Acid/Phosphorylcholine Polymer with Enhanced Lubrication and Anti-Inflammation.

Under pathological conditions, the joint is not well lubricated, which inevitably leads to osteoarthritis. Currently, in clinics injection of hyaluronic acid (HA) as an intra-articular viscosupplement is one of the main methods for alleviation of osteoarthritis. However, the viscosity of HA reduces dramatically under high shear rate due to the shear-thinning effect. Therefore, it is crucial to enhance the lubrication property of HA in order to treat osteoarthritis effectively. In this study, we successfully grafted 2-methacryloyloxyethyl phosphorylcholine (MPC), which is a zwitterionic biomaterial with excellent hydration lubrication, onto the HA with two different molecular weights (HAMPC) to enhance lubrication. The lubrication test performed using an atomic force microscope showed that, compared with HA, the friction coefficient of HAMPC was greatly reduced under various conditions. The in vitro test demonstrated that HAMPC was biocompatible and could upregulate cartilage anabolic genes while simultaneously downregulating cartilage catabolic proteases and pain-related genes. Importantly, high molecular weight HAMPC exhibited improved the capability to regulate these genes compared with low molecular weight HAMPC. In conclusion, the high molecular weight HAMPC developed herein, with enhanced lubrication and anti-inflammation, may be a promising polymer for the treatment of osteoarthritis.

Recent advance of erythrocyte-mimicking nanovehicles: From bench to bedside.

Erythrocyte-mimicking nanovehicles (EM-NVs) are developed by fusing nanoparticle cores with naturally derived erythrocyte membranes. Compared with conventional nanosystems, EM-NVs hold preferable characteristics of prolonged blood circulation time and immune evasion. Due to the cell surface mimetic properties, along with tailored core material, EM-NVs have huge application potential in a large variety of biomedical fields, which are anticipated to revolutionize the present theranostic modalities of diseases in clinic. This review focuses on (I) drug carriers, (II) photosensitizers, (III) antidotes, (IV) vaccines and (V) probes, aiming to present an overall summary of the latest advancement in the application of EM-NVs, and highlight the major challenges and opportunities in this field.

Application of biodegradable 3D-printed cage for cervical diseases via anterior cervical discectomy and fusion (ACDF): an in vitro biomechanical study.

OBJECTIVES: To design and fabricate a 3D-printed cervical cage composite of polylactic acid (PLA)/nano-sized and ß-tricalcium phosphate (ß-TCP). RESULTS: CAD analysis provided a useful platform to design the preliminary cage. In vitro cell culture and in vivo animal results showed promising results in the biocompatibility of the constructs. Endplate matching evaluation showed better matching degree of 3D-printed cages than those of conventional cages. Biomechanical evaluation showed better mechanical properties of 3D-printed cages than those of conventional cages. CONCLUSION: The novel 3D printed PLA/pß-TCP cage showed good application potential, indicating a novel, feasible, and inexpensive method to manufacture cervical fusion cages.

Reconstruct the proximal radius with iliac graft and elastic intramedullary nail fixation after tumor resection.

BACKGROUND: This study aims to introduce a novel technique in treating benign bone tumors of the proximal radius by elastic intramedullary nail fixation and iliac graft after tumor resection. METHOD: In this retrospective case series, the treatment outcomes of 17 patients with benign bone tumor involving the proximal radius were reported from January 2010 to August 2014. All the patients received reconstruction surgery with iliac graft and elastic intramedullary nail fixation after tumor resection. Pain scoring was assessed using the 0 to 10 numerical rating scale. The quality of life scoring was assessed using the SF-30 scoring system. In addition, functional outcome was assessed with the Musculoskeletal Tumor Society score and the Disabilities of the Arm, Shoulder, and Hand score. RESULTS: The mean follow-up was 16 months (range, 10-22). The average bone consolidate time was 19.2 weeks (range, 16-24 weeks). The pre- and postoperative pain scores were 5.47 ± 1.58 and 1.18 ± 0.39, respectively. The pain symptom was significantly ameliorated after the operation (t = 13.50, p < 0.01). The pre- and postoperative and the quality of life scores were 48.29 ± 6.58 and 77.47 ± 5.89, respectively; the quality of life score was dramatically improved (t = -20.11, p < 0.01). The mean Musculoskeletal Tumor Society score was 83.41 % (range, 63-93 %) and the mean Disabilities of the Arm, Shoulder, and Hand score was 14.1 (range, 5.8-38.3). CONCLUSION: Taken together, the application of iliac graft and elastic intramedullary nail fixation after excision of lesions might be associated to a significant reduction of the pain and improvement of QOL (quality of life) and limb function of patients with benign bone tumors of proximal radius.

Chromobox Homolog 4 is Positively Correlated to Tumor Growth, Survival and Activation of HIF-1α Signaling in Human Osteosarcoma under Normoxic Condition.

OBJECTIVES: The clinical significance and tumorigenesis of Chromobox homolog 4 (CBX4) have been reported in hepatocellular carcinoma. The purpose of this study is to confirm the expression, elucidate the biological function and investigate the potential mechanism of CBX4 in osteosarcoma (OS). METHODS: The expression of CBX4 in OS samples and cell lines was measured by RT-PCR and western blot test. Cell cycle, CCK8 and colony-forming assays were used to detect changes of cells growth. Cell apoptosis assay was used to measure cell survival capacity. Trans-well assay was used to test the activities of migration and invasion. The expression of genes regulated by CBX4 was detected by qRT-PCT test. RESULTS: The expression of CBX4 was up-regulated in multiple OS cell lines and clinical samples. Overexpression of CBX4 was correlated with advanced clinical stage, high degree of malignancy and low tumor necrosis rate. Moreover, knockdown of CBX4 resulted in significant inhibition of cell growth and cell survival in OS cells under normoxic condition. In addition, we found that knockdown of CBX4 lead to down-regulating of HIF-1α-targeted genes without changing HIF-1α expression itself. CONCLUSION: Taken together, CBX4 is up-regulated and has a pro-tumor effect in OS with an activation of HIF-1α signaling pathway under normoxic condition. Therefore, targeting CBX4 may provide a new therapeutic method for OS.

Efficacy of limb salvage with primary tumor resection simultaneously for solitary bone metastasis in limbs.

BACKGROUND: This study aims to evaluate the efficacy of limb salvage with primary tumor resection on patients with solitary bone metastasis. METHODS: A retrospective treatment outcome review was performed on 20 patients with solitary bone metastasis as the primary clinical symptom who were admitted to the hospital between 2006 and 2010. With primary tumor resection, 18/20 patients received limb salvage surgery simultaneously. Pain scoring was assessed using the 0 to 10 numerical rating scale. The quality of life scoring was performed before and 3 months after surgery using the SF-30 scoring system. In addition, limb function was assessed 3 months after the operation using the Scoring System of American Musculoskeletal Tumor Society system (MSTS). RESULTS: The pain symptom was significantly ameliorated after the operation (t=26.653, P<0.001), and the quality of life dramatically improved (t=-20.581, P<0.001). The postoperative MSTS scores ranged from 18 to 27. The average score was 23.10±2.36. The Kaplan-Meier analysis showed that no significant differences (χ2=1.589, P=0.207) were observed in the tumor-free survival time between the wide and marginal resections. CONCLUSIONS: The application of the wide or marginal excision for the primary lesion and bony metastasis focus, based on the principles of primary bone tumors, can significantly relieve the pain and improve the quality of life and limb function of patients whose solitary bone metastasis was manifested as the first sign.

Overexpression of X-Box Binding Protein 1 (XBP1) Correlates to Poor Prognosis and Up-Regulation of PI3K/mTOR in Human Osteosarcoma.

Increasing evidence demonstrates that dysregulation of XBP1 function contributes to tumorigenesis in some cancers. However, little is known about the role of XBP1 in the progression of osteosarcoma (OS). The expression of XBP1 in OS samples was measured by quantitative RT-PCR and Western blotting assays. Cell cycle analysis and cell counting kit 8 (CCK8) assays were performed to determine the effects of XBP1 expression on cells growth capacity. Cell apoptosis coassay was applied to determine cell survival. The expression of genes affected by XBP1 was examined by quantitative RT-RCR and validated by Western blotting assays. XBP1 was overexpressed in OS clinical samples compared with corresponding non-cancerous tissues. Overexpression of XBP1 was significantly associated with advanced clinical stages, high degree of malignancy and low tumor necrosis rate. Furthermore, hypoxia activated XBP1, and silencing XBP1 significantly enhanced OS cell apoptosis. Knock-down of XBP1 resulted in inhibition of OS growth. Most importantly, knockdown of XBP1 led to down-regulation of PIK3R3 and mTOR. Taken together, XBP1 is up-regulated and has a pro-tumor effect in OS with activation of PI3K/mTOR signaling. Thus, targeting XBP1 may provide a new potential therapeutic method for OS.

The long-term outcomes following the use of inactivated autograft in the treatment of primary malignant musculoskeletal tumor.

BACKGROUND: Biological reconstruction surgery is a tough but alluring option for treating primary malignant musculoskeletal tumors. In this article, we evaluate the clinical outcomes of primary malignant musculoskeletal tumors treated with inactivated autograft using alcohol. METHOD: In this article, we include 58 patients who had primary malignant bone tumors treated with wide resection and recycling autograft reconstruction using alcohol between January 2003 and January 2013. The outcomes were measured by recurrence, functional status, and complications. Functional status was assessed according to the Musculoskeletal Tumor Society Score (MSTSS). The Kaplan-Meier survival curve was used to evaluate the survival rate of the patient. RESULT: The most common tumor was osteosarcoma (31 cases) followed by chondrosarcoma (10 cases). The tibia was the most frequently involved skeletal site (27 cases) followed by femur (26 cases). The median follow-up period was 54 months, ranging from 18 to 96 months. In 58 patients, 12 were with local recurrence (20.7 %), 16 with lung metastasis (27.6 %), and 13 with complications (22.4 %). The main complication was infection (8 cases). The autografts survived in 49 patients (84.5 %). The mean MSTSS score was 78.5 %, ranging from 47 to 98 %. CONCLUSION: Recycling autograft reconstruction using alcohol had favorable clinical outcomes to some degree; however, the recurrence and complication rates seem to be high. Thus, we should apply this method with caution and choose the patients with strict surgical indication.