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Random skin flap grafting is the most common skin grafting technique in reconstructive surgery. Despite progress in techniques, the incidence of distal flap necrosis still exceeds 3%, which limits its use in clinical practice. Current methods for treating distal flap necrosis are still lacking. Pinocembrin (Pino) can inhibit reactive oxygen species (ROS) and cell death in a variety of diseases, such as cardiovascular diseases, but the role of Pino in random flaps has not been explored. Therefore, we explore how Pino can enhance flap survival and its specific upstream mechanisms via macroscopic examination, Doppler, immunohistochemistry, and western blot. The results suggested that Pino can enhance the viability of random flaps by inhibiting ROS, pyroptosis and apoptosis. The above effects were reversed by co-administration of Pino with adeno-associated virus-silencing information regulator 2 homolog 3 (SIRT3) shRNA, proving the beneficial effect of Pino on the flaps relied on SIRT3. In addition, we also found that Pino up-regulates SIRT3 expression by activating the AMP-activated protein kinase (AMPK) pathway. This study proved that Pino can improve random flap viability by eliminating ROS, and ROS-induced cell death through the activation of SIRT3, which are triggered by the AMPK/PGC-1α signaling pathway.
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Piroptosis , Sirtuina 3 , Humanos , Especies Reactivas de Oxígeno/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Sirtuina 3/metabolismo , Apoptosis , NecrosisRESUMEN
Surface chemistry and mechanical stability determine the osteogenic capability of bone implants. The development of high-strength bioactive scaffolds for in-situ repair of large bone defects is challenging because of the lack of satisfying biomaterials. In this study, highly bioactive Ca-silicate (CSi) bioceramic scaffolds were fabricated by additive manufacturing and then modified for pore-wall reinforcement. Pure CSi scaffolds were fabricated using a direct ink writing technique, and the pore-wall was modified with 0%, 6%, or 10% Mg-doped CSi slurry (CSi, CSi-Mg6, or CSi-Mg10) through electrostatic interaction. Modified CSi@CSi-Mg6 and CSi@CSi-Mg10 scaffolds with over 60% porosity demonstrated an appreciable compressive strength beyond 20 MPa, which was ~2-fold higher than that of pure CSi scaffolds. CSi-Mg6 and CSi-Mg10 coating layers were specifically favorable for retarding bio-dissolution and mechanical decay of scaffolds in vitro. In-vivo investigation of critical-size femoral bone defects repair revealed that CSi@CSi-Mg6 and CSi@CSi-Mg10 scaffolds displayed limited biodegradation, accelerated new bone ingrowth (4-12 weeks), and elicited a suitable mechanical response. In contrast, CSi scaffolds exhibited fast biodegradation and retarded new bone regeneration after 8 weeks. Thus, tailoring of the chemical composition of pore-wall struts of CSi scaffolds is beneficial for enhancing the biomechanical properties and bone repair efficacy.
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Materiales Biocompatibles/química , Huesos/citología , Compuestos de Calcio/química , Fracturas del Fémur/terapia , Osteogénesis , Silicatos/química , Ingeniería de Tejidos , Andamios del Tejido , Animales , Cerámica/química , Fracturas del Fémur/etiología , Fracturas del Fémur/patología , Fenómenos Mecánicos , Porosidad , ConejosRESUMEN
This study aimed to describe the 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH) status of Southeast Chinese individuals influenced by season. The secondary aim was to determine the cutoff for sufficient 25(OH)D in a four-season region. From January 2011 to June 2014, a total of 17 646 individuals were evaluated in our study. The serum levels of PTH were detected simultaneously in 5579 cases. A total of 25(OH)D and intact PTH were measured by the electrochemiluminescent immunoassay. The distribution of the concentration, prevalence and seasonal variability of 25(OH)D and PTH were studied. The mean 25(OH)D concentration in our study was 43.00(30.40) nmol/L. The prevalence of insufficiency (25(OH)D < 50 nmol/L) was 62.87% and that of deficiency (<30 nmol/L) was 28.54%. Mean serum 25(OH)D levels revealed a limited sinusoidal profile throughout the year and were significantly higher in Autumn. On the other hand, PTH levels showed an opposite response to seasonal effects relative to 25(OH)D. Age, BMI and daylight were not significantly correlated with 25(OH)D and serum PTH reached a plateau at higher values of serum 25(OH)D of 42.86 nmol/L. This study demonstrated that Vitamin D insufficiency is highly prevalent in Southeast China. The concentration of 25(OH)D in the male group was generally higher than that in the female group. Seasonal variation was an important aspect of 25(OH)D and PTH concentration. This study revealed that the optimal serum threshold of 25(OH)D for bone health should be between 40 and 50 nmol/L for Southeast Chinese individuals.
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Hormona Paratiroidea/sangre , Estaciones del Año , Vitamina D/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , China/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Vitamina D/análogos & derivados , Adulto JovenRESUMEN
BACKGROUND: Spinal cord injury (SCI) is a severe central nervous system trauma. The present study aimed to evaluate the effect of HIF-1α on inflammation in spinal cord injury (SCI) to uncover the molecular mechanisms of anti-inflammation. RESULTS: HIF-1α was reduced in SCI model rats and HIF-1α activation reduced TNF-α, IL-1ß, IL-6 and IL-18 levels in SCI model rats. Meanwhile, Circ 0001723 expression was down-regulated and miR-380-3p expression was up-regulated in SCI model rats. In vitro model, down-regulation of Circ 0001723 promoted TNF-α, IL-1ß, IL-6 and IL-18 levels, compared with control negative group. However, over-expression of Circ 0001723 reduced TNF-α, IL-1ß, IL-6 and IL-18 levels in vitro model. Down-regulation of Circ 0001723 suppressed HIF-1α protein expressions and induced NLRP3 and Caspase-1 protein expressions in vitro model by up-regulation of miR-380-3p. Next, inactivation of HIF-1α reduced the pro-inflammation effects of Circ 0001723 in vitro model. Then, si-NLRP3 also inhibited the pro-inflammation effects of Circ 0001723 in vitro model via promotion of autophagy. CONCLUSIONS: We concluded that HIF-1α reduced inflammation in spinal cord injury via miR-380-3p/ NLRP3 by Circ 0001723.
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Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Inflamación/metabolismo , MicroARNs/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , ARN Circular/genética , Traumatismos de la Médula Espinal/metabolismo , Animales , Citocinas/sangre , Regulación de la Expresión Génica , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Osteoporosis is a severe skeletal disorder. Patients have a low bone mineral density and bone structural deterioration. Mounting lines of evidence suggest that inappropriate apoptosis of osteoblasts/osteocytes leads to maladaptive bone remodelling in osteoporosis. It has been suggested that transplantation of stem cells, including mesenchymal stem cells, may alter the trajectory of bone remoulding and mitigate osteoporosis in animal models. However, stem cells needed to be carefully stored and characterized before usage. In addition, there is great batch-to-batch variation in stem cell production. Here, we fabricated therapeutic polymer microparticles from the secretome and membranes of mesenchymal stem cells (MSCs). These synthetic MSCs contain growth factors secreted by MSCs. In addition, these particles display MSC surface molecules. In vitro, co-culture with synthetic MSCs increases the viability of osteoblast cells. In a rat model of ovariectomy-induced osteoporosis, injection of synthetic MSCs mitigated osteoporosis by reducing cell apoptosis and systemic inflammation, but increasing osteoblast numbers. Synthetic MSC offers a promising therapy to manage osteoporosis.
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BACKGROUND: Chronic Achilles tendinopathy is common in the general population, and platelet-rich plasma (PRP) is seeing increased use to treat this problem. However, studies disagree as to whether PRP confers a beneficial effect for chronic Achilles tendinopathy, and no one to our knowledge has pooled the available randomized trials in a formal meta-analysis to try to reconcile those differences. QUESTIONS/PURPOSES: In the setting of a systematic review and meta-analysis of randomized controlled trials (RCTs), we asked: Does PRP plus eccentric strength training result in (1) greater improvements in Victorian Institute of Sports Assessment-Achilles (VISA-A) scores; (2) differences in tendon thickness; or (3) differences in color Doppler activity compared with placebo (saline) injections plus eccentric strength training in patients with chronic Achilles tendinopathy? METHODS: A search of peer-reviewed articles was conducted to identify all RCTs using PRP injection with eccentric training for chronic Achilles tendinopathy in the electronic databases of PubMed, Web of Science (SCI-E/SSCI/A&HCI), and EMBASE from January 1981 to August 2017. Results were limited to human RCTs and published in all languages. Two reviewers assessed study quality using the Cochrane Collaboration risk-of-bias tool. All the included studies had low risk of bias. The primary endpoint was improvement in the VISA-A score, which ranges from 0 to 100 points, with higher scores representing increased activity and less pain; we considered the minimum clinically important difference on the VISA-A to be 12 points. Secondary outcomes were tendon thickness change (with a thicker tendon representing more severe disease), color Doppler activity (with more activity representing a poorer result), and other functional measures (such as pain and return to sports activity). Four RCTs involving 170 participants were eligible and included 85 participants treated with PRP injection and eccentric training and 85 treated with saline injection and eccentric training. The patients in both PRP and placebo (saline) groups seemed comparable at baseline. We assessed for publication bias using a funnel plot and saw no evidence of publication bias. Based on previous studies, we had 80% power to detect a 12-point difference on the VISA-A score with the available sample size in each group. RESULTS: With the numbers available, there was no difference between the PRP and saline groups regarding the primary outcome (VISA-A score: mean difference [MD], 5.3; 95% confidence interval [CI], -0.7 to 11.3; p = 0.085). Likewise, we found no difference between the PRP and saline groups in terms of our secondary outcomes of tendon thickness change (MD, 0.2 mm; 95% CI, 0.6-1.0 mm; p = 0.663) and color Doppler activity (MD, 0.1; 95% CI, -0.7 to 0.4; p = 0.695). CONCLUSIONS: PRP injection with eccentric training did not improve VISA-A scores, reduce tendon thickness, or reduce color Doppler activity in patients with chronic Achilles tendinopathy compared with saline injection. Larger randomized trials are needed to confirm these results, but until or unless a clear benefit has been demonstrated in favor of the new treatment, we cannot recommend it for general use. LEVEL OF EVIDENCE: Level I, therapeutic study.
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Tendón Calcáneo , Plasma Rico en Plaquetas , Tendinopatía/terapia , Adulto , Enfermedad Crónica , Terapia por Ejercicio/métodos , Femenino , Humanos , Inyecciones , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
The chitosan/alginate-trace element-codoped octacalcium phosphate/nano-sized bioactive glass (CS/ALG-teOCP/nBG) composite membranes were prepared by a layer-by-layer coating method for the functional requirement of guided bone regeneration (GBR). The morphology, mechanical properties and moisture content of the membranes was studied by scanning electron microscopy (SEM) observation, mechanical and swelling test. The results showed that the teOCP/nBG distributed uniformly in the composite membranes, and such as-prepared composite membrane exhibited an excellent tensile strength, accompanying with mechanical decay with immersion in aqueous medium. Cell culture and MTT assays showed that the surface microstructure and the ion dissolution products from teOCP/nBG components could enhance the cell proliferation, and especially the composite membranes was suitable for supporting the adhesion and growth behavior of human bone marrow mesenchymal stem cells (hBMSCs) in comparison with the CS/ALG pure polymer membranes. These results suggest that the new CS/ALG-teOCP/nBG composite membrane is highly bioactive and biodegradable, and favorable for guiding bone regeneration.
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Alginatos/química , Regeneración Ósea/efectos de los fármacos , Fosfatos de Calcio/química , Quitosano/química , Vidrio/química , Regeneración Tisular Dirigida/métodos , Membranas Artificiales , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Supervivencia Celular/efectos de los fármacos , Ácido Glucurónico/química , Ácidos Hexurónicos/química , Humanos , Fenómenos Mecánicos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Nanoestructuras/química , Agua/químicaRESUMEN
Osteoporosis is a common disease characterized by low bone mineral density (BMD) and low trauma fractures, mainly resulting from exceeding bone resorption by osteoclasts over bone formation by osteoblasts. Circulating monocytes are directly involved in osteoclastogenesis, and lncRNAs are believed to be involved in the osteoblast differentiation. However, no study has been conducted to identify the roles of lncRNA in circulating monocytes associated with human osteoporosis. In this study, we found significant upregulation of DANCR in the blood mononuclear cells (MNCs) from low-BMD patients with the qRT-PCR analyses. We further found that DANCR promoted the expression of IL6 and TNF-α at both mRNA level and protein level in MNCs. After deletion of DANCR with siRNAs, the levels of IL6 and TNF-α are decreased in the MNCs from low-BMD postmenopausal women. Moreover, DANCR level was correlated with IL6 and TNF-α in postmenopausal women with low BMD. Furthermore, we found that DANCR-induced IL6 and TNF-α in MNCs had bone-resorbing activity. These results indicate that DANCR is involved in the pathology of osteoporosis and may be as a biomarker for postmenopausal osteoporosis.
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Monocitos/fisiología , Osteoporosis Posmenopáusica/genética , ARN Largo no Codificante/fisiología , Anciano , Densidad Ósea , Resorción Ósea/genética , Femenino , Regulación de la Expresión Génica , Marcadores Genéticos , Humanos , Interleucina-6/sangre , Interleucina-6/metabolismo , Persona de Mediana Edad , Osteoporosis Posmenopáusica/sangre , ARN Largo no Codificante/análisis , ARN Largo no Codificante/sangre , ARN Largo no Codificante/genética , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/metabolismo , Regulación hacia ArribaRESUMEN
Anterior cruciate ligament (ACL) tears are prevalent knee injures, particularly among active individuals. Accurate and timely diagnosis is essential for determining the optimal treatment strategy and assessing patient prognosis. Various previous studies have demonstrated the successful application of deep learning techniques in the field of medical image analysis. This study aimed to develop a deep learning model for detecting ACL tears in knee magnetic resonance Imaging (MRI) to enhance diagnostic accuracy and efficiency. The proposed model consists of three main modules: a Dual-Scale Data Augmentation module (DDA) to enrich the training data on both the spatial and layer scales; a selective group attention module (SG) to capture relationships across the layer, channel, and space scales; and a fusion module to explore the inter-relationships among various perspectives to achieve the final classification. To ensure a fair comparison, the study utilized a public dataset from MRNet, comprising knee MRI scans from 1250 exams, with a focus on three distinct views: axial, coronal, and sagittal. The experimental results demonstrate the superior performance of the proposed model, termed SGNET, in ACL tear detection compared with other comparison models, achieving an accuracy of 0.9250, a sensitivity of 0.9259, a specificity of 0.9242, and an AUC of 0.9747.
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Lesiones del Ligamento Cruzado Anterior , Aprendizaje Profundo , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Lesiones del Ligamento Cruzado Anterior/diagnóstico por imagen , Masculino , Adulto , Femenino , Ligamento Cruzado Anterior/diagnóstico por imagen , Ligamento Cruzado Anterior/patología , Sensibilidad y Especificidad , Adulto JovenRESUMEN
BACKGROUND: Random skin flap grafting is one of the most commonly used techniques in plastic and orthopedic surgery. However, necrosis resulting from ischemia and ischemia-reperfusion injury in the distal part of the flap can severely limit the clinical application of the flap. Studies have revealed that naringenin reduces pyroptosis, apoptosis, and necroptosis, inhibits oxidative stress, and promotes autophagy. In this study, the effects of Naringenin on flap viability and its underlying mechanism were evaluated. METHODS: Mice with random skin flaps were randomly allocated to control, Naringenin, and Naringenin + 3-methyladenine groups. On postoperative day 7, flap tissues were collected to estimate angiogenesis, necroptosis, apoptosis, pyroptosis, oxidative stress, and autophagy via hematoxylin and eosin staining, immunofluorescence, and immunohistochemistry. RESULTS: The results revealed that naringenin promoted the viability of the random flaps as well as angiogenesis, while inhibiting oxidative stress and decreasing pyroptosis, apoptosis, and necroptosis. These effects were reversed by the autophagy inhibitor 3-methyladenine. CONCLUSIONS: The findings indicated that naringenin treatment could promote flap survival by inhibiting pyroptosis, apoptosis, necroptosis, and alleviating oxidative stress, caused by the activation of autophagy.
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Flavanonas , Necroptosis , Piroptosis , Ratones , Animales , Apoptosis , Estrés Oxidativo , AutofagiaRESUMEN
Worldwide, osteoarthritis (OA) is regarded as the most widespread, distressing, and limiting chronic disease that affects degenerative joints. Currently, there is no treatment available to modify the progression of OA. The pathogenesis of OA is significantly linked with oxidative stress and pyroptosis. Astaxanthin (Ast) is a natural ketocarotenoid pigment with potent antioxidant activity and is shown to effectively alleviate cartilage damage in OA. However, its bioavailability is greatly limited due to poor water solubility, high sensitivity to light, temperature, and pH. In this study, Ast-loaded tetrahedral framework nucleic acids (tFNAs) or tFNA/Ast complexes (TAC) for Ast delivery are developed. Compared with free Ast and tFNA alone, TAC exhibits improved drug stability and cellular uptake. Most importantly, TAC effectively protects chondrocytes against oxidative stress-induced pyroptosis while promoting extracellular matrix anabolism by chondrocytes, and ultimately alleviates cartilage damage in a mouse destabilization of the medial meniscus (DMM) model. Thus, TAC holds great promise for the treatment of OA patients.
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It is known that hydroxyapatite-type calcium phosphate cement (CPC) shows appreciable self-curing properties, but the phase transformation products often lead to slow biodegradation and disappointing osteogenic responses. Herein, we developed an innovative strategy to endow invisible micropore networks, which could tune the microstructures and biodegradation of α-tricalcium phosphate (α-TCP)-based CPC by gypsum fibers, and the osteogenic capability of the composite cements could be enhanced in vivo. The gypsum fibers were prepared via extruding the gypsum powder/carboxylated chitosan (CC) slurry through a 22G nozzle (410 µm in diameter) and collecting with a calcium salt solution. Then, the CPCs were prepared by mixing the α-TCP powder with gypsum fibers (0-24 wt %) and an aqueous solution to form self-curing cements. The physicochemical characterizations showed that injectability was decreased with an increase in the fiber contents. The µCT reconstruction demonstrated that the gypsum fiber could be distributed in the CPC substrate and produce long-range micropore architectures. In particular, incorporation of gypsum fibers would tune the ion release, produce tunnel-like pore networks in vitro, and promote new bone tissue regeneration in rabbit femoral bone defects in vivo. Appropriate gypsum fibers (16 and 24 wt %) could enhance bone defect repair and cement biodegradation. These results demonstrate that the highly biodegradable cement fibers could mediate the microstructures of conventional CPC biomaterials, and such a bicomponent composite strategy may be beneficial for expanding clinical CPC-based applications.
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Sulfato de Calcio , Hidroxiapatitas , Osteogénesis , Animales , Conejos , Sulfato de Calcio/farmacología , Polvos , Fosfatos de Calcio/farmacología , Fosfatos de Calcio/química , Cementos para Huesos/farmacología , Cementos para Huesos/químicaRESUMEN
The authors describe a modified double chevron subtrochanteric shortening osteotomy combined with cementless total hip arthroplasty for Crowe type-IV hip dysplasia. Shortening the femur allows to relax the shortened musculature. This operation was performed in 18 patients (22 hips) between January 2000 and February 2006. The mean follow-up period was 5.6 years (range: 3 to 8 years). The mean amount of femoral subtrochanteric shortening was 38 mm (range: 25 to 60 mm). The mean Harris hip score improved from 47 (range: 35 to 65) preoperatively to 88 points (range: 75 to 97) at final follow-up. The Trendelenburg sign was corrected from positive to negative in 12 of 22 hips. No acetabular or femoral components loosened or required revision during the follow-up period. All osteotomy sites healed in 3 to 6 months without complications. Cementless total hip arthroplasty using the modified double chevron subtrochanteric osteotomy provided good short- to midterm results in all 22 Crowe type-IV hip dislocations. Moreover, it restored the anatomic hip center and the limb length, which contributed to correction of the preoperative limp.
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Artroplastia de Reemplazo de Cadera/métodos , Fémur/cirugía , Luxación de la Cadera/cirugía , Osteotomía/métodos , Acetábulo/cirugía , Adulto , Anciano , Femenino , Cuello Femoral/cirugía , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Osteoarthritis (OA) remains a challenging condition due to limited drug bioavailability within the avascular and dense cartilage matrix. This study introduces a pH/redox-responsive nanogel for enhanced delivery of geraniol in OA therapy. We investigated geraniol's role in preventing chondrocyte matrix degradation and designed a pH/redox-responsive nanogel as a delivery platform. Our methods included Western blot, histological staining, and immunohistochemistry. Geraniol treatment reduced Keap1 expression while elevating Nrf2 and HO-1 levels, effectively inhibiting cartilage matrix degradation. The pH/redox-responsive nanogel further enhanced geraniol's therapeutic impact. Our study demonstrates that geraniol encapsulated within a pH/redox-responsive nanogel mitigates OA by regulating oxidative stress and inflammation. This innovative approach holds potential as an effective OA therapeutic strategy.
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Cartílago Articular , Osteoartritis , Humanos , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Nanogeles/uso terapéutico , Cartílago Articular/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Osteoartritis/patología , Inflamación/patología , Condrocitos/metabolismo , Estrés Oxidativo , Oxidación-Reducción , Concentración de Iones de HidrógenoRESUMEN
Silicate-based biomaterials-clinically applied fillers and promising candidates-can act as a highly biocompatible substrate for osteostimulative osteogenic cell growth in vitro and in vivo. These biomaterials have been proven to exhibit a variety of conventional morphologies in bone repair, including scaffolds, granules, coatings and cement pastes. Herein, we aim to develop a series of novel bioceramic fiber-derived granules with core-shell structures which have a hardystonite (HT) shell layer and changeable core components-that is, the chemical compositions of a core layer can be tuned to include a wide range of silicate candidates (e.g., wollastonite (CSi)) with doping of functional ions (e.g., Mg, P, and Sr). Meanwhile, it is versatile to control the biodegradation and bioactive ion release sufficiently for stimulating new bone growth after implantation. Our method employs rapidly gelling ultralong core-shell CSi@HT fibers derived from different polymer hydrosol-loaded inorganic powder slurries through the coaxially aligned bilayer nozzles, followed by cutting and sintering treatments. It was demonstrated that the nonstoichiometric CSi core component could contribute to faster bio-dissolution and biologically active ion release in tris buffer in vitro. The rabbit femoral bone defect repair experiments in vivo indicated that core-shell bioceramic granules with an 8% P-doped CSi-core could significantly stimulate osteogenic potential favorable for bone repair. It is worth concluding that such a tunable component distribution strategy in fiber-type bioceramic implants may develop new-generation composite biomaterials endowed with time-dependent biodegradation and high osteostimulative activities for a range of bone repair applications in situ.
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Materiales Biocompatibles , Regeneración Ósea , Animales , Conejos , Porosidad , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/química , Osteogénesis , Silicatos/farmacología , Silicatos/químicaRESUMEN
The pore architecture of porous scaffolds is a critical factor in osteogenesis, but it is a challenge to precisely configure strut-based scaffolds because of the inevitable filament corner and pore geometry deformation. This study provides a pore architecture tailoring strategy in which a series of Mg-doped wollastonite scaffolds with fully interconnected pore networks and curved pore architectures called triply periodic minimal surfaces (TPMS), which are similar to cancellous bone, are fabricated by a digital light processing technique. The sheet-TPMS pore geometries (s-Diamond, s-Gyroid) contribute to a 3â4-fold higher initial compressive strength and 20%-40% faster Mg-ion-release rate compared to the other-TPMS scaffolds, including Diamond, Gyroid, and the Schoen's I-graph-Wrapped Package (IWP) in vitro. However, we found that Gyroid and Diamond pore scaffolds can significantly induce osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Analyses of rabbit experiments in vivo show that the regeneration of bone tissue in the sheet-TPMS pore geometry is delayed; on the other hand, Diamond and Gyroid pore scaffolds show notable neo-bone tissue in the center pore regions during the early stages (3-5 weeks) and the bone tissue uniformly fills the whole porous network after 7 weeks. Collectively, the design methods in this study provide an important perspective for optimizing the pore architecture design of bioceramic scaffolds to accelerate the rate of osteogenesis and promote the clinical translation of bioceramic scaffolds in the repair of bone defects.
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Correction for 'Core-shell bioceramic fiber-derived biphasic granules with adjustable core compositions for tuning bone regeneration efficacy' by Zhaonan Bao et al., J. Mater. Chem. B, 2023, 11, 2417-2430, https://doi.org/10.1039/D3TB90052E.
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The pore morphology design of bioceramic scaffolds plays a substantial role in the induction of bone regeneration. Specifically, the effects of different scaffold pore geometry designs on angiogenesis and new bone regeneration remain unclear. Therefore, we fabricated Mg/Sr co-doped wollastonite bioceramic (MS-CSi) scaffolds with three different pore geometries (gyroid, cylindrical, and cubic) and compared their effects on osteogenesis and angiogenesis in vitro and in vivo. The MS-CSi scaffolds were fabricated by digital light processing (DLP) printing technology. The pore structure, mechanical properties, and degradation rate of the scaffolds were investigated. Cell proliferation on the scaffolds was evaluated using CCK-8 assays while angiogenesis was assessed using Transwell migration assays, tube formation assays, and immunofluorescence staining. The underlying mechanism was explored by western blotting. Osteogenic ability of scaffolds was evaluated by alkaline phosphatase (ALP) staining, western blotting, and qRT-PCR. Subsequently, a rabbit femoral defect model was prepared to compare differences in the scaffolds in osteogenesis and angiogenesis in vivo. Cell culture experiments showed that the gyroid pore scaffold downregulated YAP/TAZ phosphorylation and enhanced YAP/TAZ nuclear translocation, thereby promoting proliferation, migration, tube formation, and high expression of CD31 in human umbilical vein endothelial cells (HUVECs) while strut-based (cubic and cylindrical pore) scaffolds promoted osteogenic differentiation in bone marrow mesenchymal stem cells and upregulation of osteogenesis-related genes. The gyroid pore scaffolds were observed to facilitate early angiogenesis in the femoral-defect model rabbits while the strut-based scaffolds promoted the formation of new bone tissue. Our study indicated that the pore geometries and pore curvature characteristics of bioceramic scaffolds can be precisely tuned for enhancing both osteogenesis and angiogenesis. These results may provide new ideas for the design of bioceramic scaffolds for bone regeneration.
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Background: Postoperative non-union of femoral neck fracture often needs secondary operation. We report a case of a postoperative non-union of femoral neck fracture treated with teriparatide. Case presentation: A young male patient with Garden IV femoral neck fracture who showed no obvious signs of healing 3 months after percutaneous hollow nail fixation in which the fracture line was enlarged and the hollow nail was withdrawn. Bone non-union healed after 6 months of continuous subcutaneous injection of teriparatide at a dosage of 20â mg/day after the patient refused a secondary surgery. As far as we know, there have been no relevant reports on this type of fracture yet. Conclusions: Teriparatide is expected to be beneficial in treating young patients with a displaced femoral neck fracture who have difficulty in healing from non-union and who are keen on avoiding secondary surgery.
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The development of injectable cement-like biomaterials via a minimally invasive approach has always attracted considerable clinical interest for modern bone regeneration and repair. Although α-tricalcium phosphate (α-TCP) powders may readily react with water to form hydraulic calcium-deficient hydroxyapatite (CDHA) cement, its long setting time, poor anti-collapse properties, and low biodegradability are suboptimal for a variety of clinical applications. This study aimed to develop new injectable α-TCP-based bone cements via strontium doping, α-calcium sulfate hemihydrate (CSH) addition and liquid phase optimization. A combination of citric acid and chitosan was identified to facilitate the injectable and anti-washout properties, enabling higher resistance to structure collapse. Furthermore, CSH addition (5 %-15 %) was favorable for shortening the setting time (5-20 min) and maintaining the compressive strength (10-14 MPa) during incubation in an aqueous buffer medium. These α-TCP-based composites could also accelerate the biodegradation rate and new bone regeneration in rabbit lateral femoral bone defect models in vivo. Our studies demonstrate that foreign ion doping, secondary phase addition and liquid medium optimization could synergistically improve the physicochemical properties and biological performance of α-TCP-based bone cements, which will be promising biomaterials for repairing bone defects in situations of trauma and diseased bone.