RESUMO
Tumorous bone defects present significant challenges for surgical bio-reconstruction due to the dual pathological conditions of residual tumor presence and extensive bone loss following excision surgery. To address this challenge, a "thermal switch" smart bone scaffold based on the silicene nanosheet-modified decalcified bone matrix (SNS@DBM) is developed by leveraging the natural affinity between collagen and silicene, which is elucidated by molecular dynamics simulations. Benefitting from its exceptional photothermal ability, biodegradability, and bioactivity, the SNS@DBM "thermal switch" provides an integrated postoperative sequential thermotherapy for tumorous bone loss by exerting three levels of photothermal stimulation (i.e., strong, moderate, and nonstimulation). During the different phases of postoperative bioconstruction, the SNS@DBM scaffold realizes simultaneous residual tumor ablation, tumor recurrence prevention, and bone tissue regeneration. These biological effects are verified in the tumor-bearing nude mice of patient-derived tissue xenografts and critical cranium defect rats. Mechanism research prompts moderate heat stimulus generated by and coordinating with SNSs can upregulate osteogenic genes, promote macrophages M2 polarization, and intensify angiogenesis of H-type vessels. This study introduces a versatile approach to the management of tumorous bone defects.
RESUMO
Background: Recently, a locking plate (LP) combined with a suture button was applied for distal clavicle Neer type IIb fractures. However, to our knowledge, there is limited information on clinical outcomes surrounding locking plates combined with a suture button in the treatment of Neer type IIb distal clavicle fractures. The aim of this study was to compare the outcomes among three different fixation techniques for the treatment of Neer type IIb distal clavicle fractures. Methods: We performed a retrospective cohort study of 53 patients with Neer type IIb distal clavicle fractures who were treated with a hook plate (HP group, 16 patients), a locking plate alone (LP group, 18 patients), or a locking plate with a suture button (LPSB group, 19 patients) in our hospital between March 2014 and August 2019. The clinical and radiological outcomes were evaluated, including union time, postoperative complications, and function of the shoulder joint. Results: The follow-up period was at least 2 years for all patients. All patients in the LPSB group achieved bone healing at the final follow-up. No significant differences were observed, including age, sex, side, time to surgery, duration of surgery, and mean follow-up period among the three groups (p > 0.05). The union time was shorter in the LPSB group than in the other two groups (p < 0.05). Postoperative complications were lower in the LPSB group than in the other two groups (p < 0.05). The visual analog scale score and Constant-Murley score in the LPSB group were better than those in the other groups at 3 and 6 months postoperatively (p < 0.05). Conclusion: Compared with HP and LP alone, LPSB yields better clinical outcomes and lower complication rates in the treatment of Neer type IIb distal clavicle fractures.
RESUMO
Background: Osteoid osteoma is a common benign bone tumor, and clinically there is severe local pain that typically worsens at night. The conventional CT-guided radiofrequency ablation (RFA) was widely used in the treatment of osteoid osteoma (OO), which could result in some radiation-related and imprecise complications due to the overdose of radiation exposure. This study aimed to compare the surgical effect of robot-assisted RFA with O-arm navigation and conventional CT-guided RFA in the treatment of OO. Methods: Sixty-two patients who underwent robot-assisted RFA with O-arm navigation (Robot-RFA, n = 24) or CT-guided RFA (CT-RFA, n = 38) were included in this retrospective cohort study. The mean follow-up time was 23.3 months. The intra-operative data, primary technical success rate, visual analog scale (VAS), and post-operative complications were analyzed. Results: Primary technical success was obtained in 23 patients who had robot-assisted RFA, and 35 patients who had conventional CT-guided RFA. One patient in Robot-RFA group and three patients in CT-RFA group with pain recurrence received repeat-RFA and had a secondary success. Mean operation time and dose of radiation exposure were lower in Robot-RFA group than that in CT-RFA group. The Robot-RFA group took fewer K-wire adjustment times for each patient than the CT-RFA group. There was a statistically significant difference in the mean operation time, dose of radiation exposure, and K-wire adjustment times between the groups (p < 0.05). No complications associated with the procedure were reported in the two groups during the follow-up period. Conclusion: Robot-assisted RFA with O-arm navigation is a safer and more precise strategy in the treatment of osteoid osteoma with less operation time and radiation exposure compared with the conventional CT-guided radiofrequency ablation.
RESUMO
An electrical signal is the key basis of normal physiological function of the nerve, and the stimulation of the electric signal also plays a very special role in the repair process of nerve injury. Electric stimulation is shown to be effective in promoting axonal regeneration and myelination, thereby promoting nerve injury repair. At present, it is considered that electric conduction recovery is a key aspect of regeneration and repair of long nerve defects. Conductive neural scaffolds have attracted more and more attention due to their similar electrical properties and good biocompatibility with normal nerves. Herein, PCL and MXene-PCL nerve guidance conduits (NGCs) were prepared; their effect on nerve regeneration was evaluated in vitro and in vivo. The results show that the NGCs have good biocompatibility in vitro. Furthermore, a sciatic nerve defect model (15 mm) of SD rats was made, and then the fabricated NGCs were implanted. MXene-PCL NGCs show similar results with the autograft in the sciatic function index, electrophysiological examination, angiogenesis, and morphological nerve regeneration. It is possible that the conductive MXene-PCL NGC could transmit physiological neural electric signals, induce angiogenesis, and stimulate nerve regeneration. This paper presents a novel design of MXene-PCL NGC that could transmit self-originated electric stimulation. In the future, it can be combined with other features to promote nerve regeneration.
RESUMO
BACKGROUND: Skin injury and the resultant defects are common clinical problems, and usually lead to chronic skin ulcers and even life-threatening diseases. Copper, an essential trace element of human body, has been reported to promote the regeneration of skin by stimulating proliferation of endothelial cell and enhance angiogenesis. RESULTS: Herein, we have prepared a new donut-like metal-organic frameworks (MOF) of copper-nicotinic acid (CuNA) by a simple solvothermal reaction. The rough surface of CuNA is beneficial for loading/release basic fibroblast growth factor (bFGF). The CuNAs with/without bFGF are easily processed into a light-responsive composite hydrogel with GelMA, which not only show excellent mechanical properties, but also display superior biocompatibility, antibacterial ability and bioactivity. Moreover, in the in vivo full-thickness defect model of skin wound, the resultant CuNA-bFGF@GelMA hydrogels significantly accelerate the wound healing, by simultaneously inhibiting the inflammatory response, promoting the new blood vessels formation and the deposition of collagen and elastic fibers. CONCLUSIONS: Considering the superior biocompatibility, antibacterial ability and bioactivity, the CuNA and its composite light-responsive hydrogel system will be promising in the applications of skin and even other tissue regeneration.
Assuntos
Fator 2 de Crescimento de Fibroblastos/farmacologia , Hidrogéis/química , Estruturas Metalorgânicas/química , Pele/patologia , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Força Compressiva , Cobre/química , Fator 2 de Crescimento de Fibroblastos/genética , Fator 2 de Crescimento de Fibroblastos/metabolismo , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Hidrogéis/farmacologia , Camundongos , Niacina/química , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/farmacologiaRESUMO
Doxorubicin is one of the most frequently used chemotherapy drugs in the treatment of osteosarcoma (OS), but the emergence of chemoresistance often leads to treatment failure. CXC motif chemokine receptor 4 (CXCR4) has been demonstrated to regulate OS progression and metastasis. However, whether CXCR4 is also involved in OS chemoresistance and its molecular mechanisms has yet to be fully elucidated. In the present study, CXCR4mediated autophagy for OS chemotherapy was investigated by western blot analysis, transmission electron microscopy and confocal microscopy. CXCR4 silencing enhanced doxorubicininduced apoptosis by reducing Pglycoprotein in CXCR4+ LM8 cells, while CXCR4 overexpression promoted OS doxorubicin resistance in CXCR4 Dunn cells. Furthermore, CXCR4 silencing with or without doxorubicin increased the expression of beclin 1 and light chain 3B, and the number of autophagosomes and autolysosomes, as well as induced autophagic flux activation by suppressing the PI3K/AKT/mTOR signaling pathway. In addition, pretreatment with the autophagy inhibitor bafilomycin A1 attenuated CXCR4 abrogationinduced cell death. Finally, the CXCR4 antagonist AMD3100 synergistically reinforced the antitumor effect of doxorubicin in an orthotopic OS mouse model. Taken together, the present study revealed that CXCR4 inhibition sensitizes OS to doxorubicin by inducing autophagic cell death. Therefore, targeting the CXCR4/autophagy axis may be a promising therapeutic strategy to overcome OS chemotherapy resistance.
Assuntos
Benzilaminas/administração & dosagem , Neoplasias Ósseas/tratamento farmacológico , Ciclamos/administração & dosagem , Doxorrubicina/administração & dosagem , Osteossarcoma/tratamento farmacológico , Receptores CXCR4/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Morte Celular Autofágica/efeitos dos fármacos , Benzilaminas/farmacologia , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ciclamos/farmacologia , Doxorrubicina/farmacologia , Sinergismo Farmacológico , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores CXCR4/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Preoperative posterior tilt is a risk factor for fixation failure in femoral neck fractures. This study aimed to evaluate the configuration of anterior positioning screw in proximal femoral plating in the treatment of retroverted femoral neck fractures in terms of resisting posterior tilt. METHODS: We retrospectively analyzed patients with retroverted femoral neck fractures who were fixed by proximal femoral plating from January 2014 to August 2019. All patients were divided into two groups according to screw configuration: anterior long-threaded screw (ALTS, n = 36) and normally short-threaded screws (NTS, n = 46). Baseline characteristics were reviewed and radiological and clinical outcomes were analyzed. Logistic regression analysis was used to identify risk factors for developing posterior tilt. RESULTS: Age, gender, Garden classification, posterior comminution, and reduction quality showed no significant difference between the groups. Increased posterior tilt was lower in the ALTS group (3.2°, 2.1-4.3°) than that in the NTS group (5.3°, 4.2-8.3°) (p < 0.001), and the percentage of people with > 5° of posterior tilt was also lower in the ALTS group (5, 13.9% vs. 24, 52.2%; p < 0.001). Femoral neck shortening (FNS) was lower in the ALTS group (3.1 (2.1-4.7) mm vs. 4.3 (3.1-6.3) mm, p = 0.003), though not statistically significant when using 5 mm as the cut-off value. Harris Hip Score in the ALTS group was higher than that in the NTS group (87.0, 84.0-90.0 vs. 82.0, 76.0-84.5; p < 0.001). Postoperative complications including delayed union, nonunion, and avascular necrosis were comparable between the groups. Multivariable analysis identified posterior comminution (OR 15.9, 95% CI 3.6-70.3, p < 0.001), suboptimal reduction quality (OR 12.0, 95% CI 2.6-56.1, p = 0.002), and NTS configuration (reference: ALTS configuration) (OR 21.9, 95% CI 4.1-116.4, p < 0.001) as risk factors for developing posterior tilt. CONCLUSIONS: Configuration of anterior positioning screw in proximal femoral plating provides better resistance against posterior tilt in the fixation of retroverted femoral neck fractures. Also, posterior comminution, suboptimal reduction, and NTS configuration (reference: ALTS) are risk factors for developing posterior tilt. TRIAL REGISTRATION: The trial registration number was ChiCTR2000039482 .
Assuntos
Placas Ósseas , Parafusos Ósseos , Fraturas do Colo Femoral/cirurgia , Fixação Interna de Fraturas/métodos , Complicações Pós-Operatórias/etiologia , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVES: Dual plate fixation has been reported to be effective in the treatment of comminuted distal femur fractures (DFFs). However, optimized use of the medial plate and screws is less studied. This study aimed to evaluate the effect of a hybrid configuration of the medial plate in dual plate fixation of comminuted DFFs in promoting fracture healing. MATERIALS AND METHODS: We retrospectively analyzed 62 patients with comminuted DFFs (AO/OTA 33-A3/33-C2/33-C3) from January 2015 to March 2020, who were either fixed with lateral locked plating augmented with hybrid locked medial plating (LP-HLMP, n = 32) or lateral locked plating (LLP, n = 30) alone. Specifically, compression screws were applied in the middle of the medial plate and flanked by locking ones at both ends. Baseline characteristics, radiological and clinical outcomes were reviewed and analyzed. Multivariate logistic regression analysis was used to identify predictive factors for early fracture healing, and risk factors for delayed union/nonunion. RESULTS: Demographics including age, gender, smoking, diabetes, and injury mechanism were comparable between the two groups. Reduction quality was better in the LP-HLMP group (p < 0.001). Although the LP-HLMP group experienced longer duration of surgery (125 min vs. 100 min, p < 0.001), sign of healing at 3 months was more obvious in this group (75%, 24/32 vs. 30%, 9/30; p < 0.001). The LP-HLMP group also presented with higher union rate (93.8%, 30/32 vs. 56.7%, 17/30; p = 0.001) and lower reoperation rate (0%, 0/32 vs. 13.3%, 4/30; p = 0.049). Kolment score showed no statistical significance between the two groups. Multivariate analysis revealed that younger age (< 60 years) (OR 5.99, 95%CI 1.16 - 31.03; p = 0.001) and LP-HLMP fixation (OR 45.90, 95% CI 4.78 - 440.56; p = 0.001) predict early healing; while smoking (OR 17.80, 95% CI 2.41 - 131.49; p = 0.01) and fracture translation (OR 3.49, 95% CI 1.46 - 8.32; p = 0.01) were identified as risk factors for delayed union/nonunion. CONCLUSION: Hybrid locked medial plating in this study favors the healing of comminuted DFFs and reduces reoperation. Additionally, smoking and suboptimal reduction (translation) predict delayed union/nonunion.
Assuntos
Fraturas do Fêmur , Fraturas Cominutivas , Placas Ósseas , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/cirurgia , Fêmur , Fixação Interna de Fraturas , Consolidação da Fratura , Fraturas Cominutivas/diagnóstico por imagem , Fraturas Cominutivas/cirurgia , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: Pauwels type-3 femoral neck fractures are challenging injuries to manage with high rates of complications after internal fixation and no consensus has been reached regarding the optimal fixation construct. The current study aims to evaluate the effect of dynamic limited axial compression in parallel screws combined with medial buttress plate (SMBP) or lateral compression plate (LCP) fixation of Pauwels type-3 femoral neck fractures. METHODS: We performed a retrospective analysis of 51 cases of Pauwels type-3 femoral neck fractures who were fixed by SMBP or LCP. Specifically, the screw fixing the femoral head in the buttress plate was omitted. Postoperative complications and functional outcomes were mainly studied. RESULTS: With a mean follow-up of 19.9 months, the rate of neck shortening was higher in the LCP group than that in SMBP group (32.1% vs. 8.7%, p = 0.04). Neither nonunion nor avascular necrosis was observed in both groups. Good-to-excellent Harris hip score accounts for 95.2% in SMBP group and 89.3% in LCP group (p = 0.40). Moreover, older age, fracture comminution and compression plate fixation predispose to neck shortening. CONCLUSION: Dynamic limited axial compression by SMBP or LCP fixation was effective to improve the functional outcome of patients with Pauwels type-3 femoral neck fractures.
Assuntos
Fraturas do Colo Femoral , Idoso , Parafusos Ósseos , Fraturas do Colo Femoral/diagnóstico por imagem , Fraturas do Colo Femoral/cirurgia , Fixação Interna de Fraturas , Consolidação da Fratura , Humanos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
One-dimensional hydroxyapatite (HA) particularly mimics the structure of mineralized collagen fibrils and displays superior mechanical properties such as toughness. Herein, we report Se-doped HA/chitosan (Se-HA/CS) biopapers constructed with self-assembled Se-doped HA nanowires and chitosan. The Se-HA/CS biopapers with high flexibility and manufacturability can not only be further processed into arbitrary shapes by folding or using scissors but also display high performances in in vitro/vivo anti-bone tumor studies. The Se-HA/CS biopapers are more inclined to inhibit the growth of tumor cells (HCS 2/8 and SJSA cells) than that of normal human bone marrow stromal cells (hBMSCs). The potential mechanisms of this meaningful anti-tumor effect were investigated, such as reactive oxygen species accumulation and the activation of apoptosis and the underlying signal pathway involved (including caspase family, Bcl-2 family and JNK/STAT3). The results demonstrate that Se-HA/CS biopapers may inhibit the growth of HCS 2/8 and SJSA cells by synchronously inducing JNK activation and STAT3 inhibition and consequently promote the apoptosis of these cells. Furthermore, the in vivo anti-tumor studies confirm that the Se-HA/CS biopapers obviously suppress the growth of patient-derived xenograft tumor models.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Ósseas/patologia , Durapatita/química , Selênio/química , Selênio/farmacologia , Animais , Linhagem Celular Tumoral , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Nanofios/química , Papel , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
In vivo mineralization is a multistep process involving mineral-protein complexes and various metastable compounds in vertebrates. In this complex process, the minerals produced in the mitochondrial matrix play a critical role in initiating extracellular mineralization. However, the functional mechanisms of the mitochondrial minerals are still a mystery. Herein, an in vitro enzymatic reaction strategy is reported for the generation of biomimic amorphous calcium phosphate (EACP) nanominerals by an alkaline phosphatase (ALP)-catalyzed hydrolysis of adenosine triphosphate (ATP) in a weakly alkalescent aqueous condition (pH 8.0-8.5), which is partially similar to the mitochondrial environment. Significantly, the EACP nanomineral obviously promotes autophagy and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by activating an AMPK related pathway, and displays a high performance in promoting bone regeneration. These results provide in vitro evidence for the effect of ATP on the formation and stabilization of the mineral in the mineralization process, demonstrating a potential strategy for the preparation of the biomimic mineral for treating bone related diseases.
Assuntos
Biomimética/métodos , Fosfatase Alcalina/metabolismo , Autofagia/fisiologia , Fosfatos de Cálcio/química , Diferenciação Celular/fisiologia , Humanos , Concentração de Íons de Hidrogênio , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Osteogênese/fisiologiaRESUMO
Biocompatibility, biodegradability and bioactivity are significantly important in practical applications of various biomaterials for bone tissue engineering. Herein, we develop a functional inorganic-organic hybrid system of calcium phosphate-phosphorylated adenosine (CPPA). Both calcium phosphate and phosphorylated adenosine molecules in CPPA are fundamental components in mammalians and play important roles in biological metabolism. In this work, we report our three leading research qualities: (1) CPPA hybrid microspheres with hollow and porous structure are synthesized by a facile one-step microwave-assisted solvothermal method; (2) CPPA hybrid microspheres show high doxorubicin loading capacity and pH-responsive drug release properties, and demonstrate positive therapeutic effects on six osteosarcoma cell lines in vitro and a mouse model of 143B osteosarcoma subcutaneous tumor in vivo; (3) CPPA hybrid microspheres are favorable to promote osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs) by activating the AMPK pathway, with satisfactory evidences from cellular alkaline phosphatase staining, alizarin red staining, real time PCR and western analysis. The as-prepared CPPA hybrid microspheres are promising in anti-osteosarcoma and bone regeneration, which simultaneously display excellent properties on drug delivery and osteogenic differentiation of hBMSCs.
Assuntos
Adenosina/administração & dosagem , Fosfatos de Cálcio/administração & dosagem , Cápsulas/síntese química , Doxorrubicina/administração & dosagem , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Osteossarcoma/tratamento farmacológico , Implantes Absorvíveis , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/química , Antineoplásicos/administração & dosagem , Cápsulas/administração & dosagem , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Linhagem Celular Tumoral , Doxorrubicina/química , Feminino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Osteoblastos/citologia , Osteoblastos/fisiologia , Osteogênese/efeitos dos fármacos , Osteogênese/fisiologia , Osteossarcoma/patologia , Fosforilação , Porosidade , Resultado do TratamentoRESUMO
Peripheral nerve injuries represent a great challenge for surgeons. The conductive neural scaffold has experienced increasing interest because of its good biocompatibility and similar electrical properties as compared to those of a normal nerve. Herein, nerve conduits made from poly(d,l-lactide)-co-poly(ethylene glycol) and polypyrrole (20%, 30%, and 50%) (PELA-PPY) were prepared by electrospinning, and used in regeneration of peripheral nerve defects. The results of an in vitro experiment indicated a high biocompatibility for the as-prepared materials, supporting the attachment and proliferation of a rat pheochromocytoma PC-12 cell. Furthermore, the PELA-PPY nerve conduit implanted in the sciatic nerve defects (10 mm) of the Spraguee-Dawley rats for 12 weeks showed similar results with the autograft, while it demonstrated a better outcome than the PELA nerve conduit in electrophysiological examination, sciatic function index, total amount of regenerated myelinated nerve fibers, axon diameter, myelin thickness, and several immunohistochemistry indices (S-100, laminin, neurofilament, bromodeoxyuridine, and glial fibrillary acidic portein). We supposed that the bioactivity is mainly generated by the PPY in composite nanofibers which could transmit self-originated electrical stimulation between cells. Due to the facile preparation and excellent in vivo performance, the PPY-PELA nerve conduit is promising for use as a bioengineered biomaterial for peripheral nerve regeneration.