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1.
Bone Res ; 11(1): 65, 2023 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-38123549

RESUMEN

The skeleton is a highly innervated organ in which nerve fibers interact with various skeletal cells. Peripheral nerve endings release neurogenic factors and sense skeletal signals, which mediate bone metabolism and skeletal pain. In recent years, bone tissue engineering has increasingly focused on the effects of the nervous system on bone regeneration. Simultaneous regeneration of bone and nerves through the use of materials or by the enhancement of endogenous neurogenic repair signals has been proven to promote functional bone regeneration. Additionally, emerging information on the mechanisms of skeletal interoception and the central nervous system regulation of bone homeostasis provide an opportunity for advancing biomaterials. However, comprehensive reviews of this topic are lacking. Therefore, this review provides an overview of the relationship between nerves and bone regeneration, focusing on tissue engineering applications. We discuss novel regulatory mechanisms and explore innovative approaches based on nerve-bone interactions for bone regeneration. Finally, the challenges and future prospects of this field are briefly discussed.


Asunto(s)
Enfermedades Óseas , Ingeniería de Tejidos , Humanos , Materiales Biocompatibles/metabolismo , Huesos/metabolismo , Neurogénesis
3.
Adv Healthc Mater ; 12(3): e2201349, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36325633

RESUMEN

Repairing infected bone defects is a challenge in the field of orthopedics because of the limited self-healing capacity of bone tissue and the susceptibility of refractory materials to bacterial activity. Innervation is the initiating factor for bone regeneration and plays a key regulatory role in subsequent vascularization, ossification, and mineralization processes. Infection leads to necrosis of local nerve fibers, impeding the repair of infected bone defects. Herein, a biomaterial that can induce skeletal-associated neural network reconstruction and bone regeneration with high antibacterial activity is proposed for the treatment of infected bone defects. A photosensitive conductive hydrogel is prepared by incorporating magnesium-modified black phosphorus (BP@Mg) into gelatin methacrylate (GelMA). The near-infrared irradiation-based photothermal and photodynamic treatment of black phosphorus endows it with strong antibacterial activity, improving the inflammatory microenvironment and reducing bacteria-induced bone tissue damage. The conductive nanosheets and bioactive ions released from BP@Mg synergistically improve the migration and secretion of Schwann cells, promote neurite outgrowth, and facilitate innerved bone regeneration. In an infected skull defect model, the GelMA-BP@Mg hydrogel shows efficient antibacterial activity and promotes bone and CGRP+ nerve fiber regeneration. The phototherapy conductive hydrogel provides a novel strategy based on skeletal-associated innervation for infected bone defect repair.


Asunto(s)
Regeneración Ósea , Hidrogeles , Antibacterianos/farmacología , Gelatina/farmacología , Hidrogeles/farmacología , Osteogénesis , Fósforo/farmacología , Animales
4.
Biomater Adv ; 139: 212979, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35882135

RESUMEN

Cutaneous wound healing, especially diabetic wound healing, is a common clinical problem. Reactive oxygen species (ROS) and bacterial infection are two major factors in the induction of oxidative stress and inflammation, leading to impeded angiogenesis and wound healing. However, it is still very difficult to reverse the harsh microenvironment of chronic inflammation and excessive oxidative stress on diabetic wound. Itaconate, an endogenous metabolite, has recently attracted extensive attention as a critical immune-regulator. In this study, we used 4-octyl itaconate (4OI), a cell-permeable itaconate derivative, to have antioxidative and anti-inflammatory functions for diabetic wound regeneration. Simultaneously, an injectable, self-healing, and antibacterial dynamic coordinative hydrogel was manufactured by binding the 4-arm polyethylene glycol (PEG) with silver nitrate to deliver the bioactive molecule. In vitro experiments confirmed that 4OI@PEG hydrogel could inhibit bacterial growth, protect human umbilical vein endothelial cells from ROS damage and enhance neovascularization. In addition, the hydrogel increased mitochondrial polarization and reduced mitochondrial fragmentation by activating the Keap1-Nrf2 antioxidant defense system. In vivo experiments proved that this multifunctional hydrogel facilitated diabetic wound healing by inhibiting local inflammation and promoting angiogenesis. Collectively, 4OI-loaded multifunctional materials could reverse various unfavorable microenvironments, such as excessive oxidative stress, inflammation, and infection, and can promote neovascularization; thus, such materials show great promise for the treatment of diabetic ulcers.


Asunto(s)
Diabetes Mellitus , Hidrogeles , Antibacterianos/farmacología , Antioxidantes/farmacología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Hidrogeles/farmacología , Inflamación , Proteína 1 Asociada A ECH Tipo Kelch , Factor 2 Relacionado con NF-E2 , Especies Reactivas de Oxígeno , Succinatos , Cicatrización de Heridas
5.
Orthop Surg ; 14(8): 1583-1592, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35706090

RESUMEN

OBJECTIVES: In geriatric acetabular fractures, the quadrilateral surface (QLS) was frequently involved in acetabular fracture patterns and accompanied by medial displacement. It was important to buttress the medial displaced QLS and reconstruct the congruity of the affected acetabulum. To evaluate the clinical effectiveness of the novel infra-pectineal quadrilateral surface buttress plates for the treatment of geriatric acetabular fractures. METHODS: Twenty-three geriatric patients who were treated for acetabular fractures involving QLS with the novel infra-pectineal buttress plates (NIBP) through a single supra-ilioinguinal approach between January 2015 and June 2019 were retrospectively analyzed; all patients received at least 1 year's follow-up. All patients were aged ≥60 years old and including 18 males and five females. Radiologic and clinical outcomes of patients involved in the study were collated and analyzed according to the Matta scoring system and the Merle D'Aubigné-Postel scoring system. The functional recovery scoring was compared using q-test. RESULTS: All 23 consecutive patients had relatively satisfactory clinical treatment effectiveness. Average ages, length of incision, operation time, and intraoperative blood loss were 69.8 ± 6.1 years, 12.1 ± 2.6 cm, 166.5 ± 43.5 min, and 500 (500,700) ml, respectively. According to the Matta scoring system, 14 cases of reduction were graded as excellent, five as good, and four as fair. At the last follow-up, the clinical outcome evaluation was excellent in 13 cases, good in seven cases, and poor in three cases with the use of the Merle D'Aubigné-Postel scoring system. The difference of modified Merle D'Aubigne-Postel score at 3 months, 6 months and last follow up was statistically significant (F = 21.56, p < 0.05). Postoperative lateral femoral cutaneous nerve injury occurred in three patients and heterotopic ossification occurred in one patient. CONCLUSIONS: For the treatment of geriatric acetabular fractures, the NIBP could provide stable and effective fixation to the QLS involved acetabular fractures, and related satisfactory clinical results with few complications were noted.


Asunto(s)
Fracturas Óseas , Fracturas de Cadera , Fracturas de la Columna Vertebral , Acetábulo/lesiones , Acetábulo/cirugía , Anciano , Placas Óseas , Femenino , Fijación Interna de Fracturas/métodos , Fracturas Óseas/cirugía , Fracturas de Cadera/cirugía , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Fracturas de la Columna Vertebral/cirugía , Resultado del Tratamiento
7.
Bioact Mater ; 16: 271-284, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35386320

RESUMEN

Angiogenesis and neurogenesis play irreplaceable roles in bone repair. Although biomaterial implantation that mimics native skeletal tissue is extensively studied, the nerve-vascular network reconstruction is neglected in the design of biomaterials. Our goal here is to establish a periosteum-simulating bilayer hydrogel and explore the efficiency of bone repair via enhancement of angiogenesis and neurogenesis. In this contribution, we designed a bilayer hydrogel platform incorporated with magnesium-ion-modified black phosphorus (BP) nanosheets for promoting neuro-vascularized bone regeneration. Specifically, we incorporated magnesium-ion-modified black phosphorus (BP@Mg) nanosheets into gelatin methacryloyl (GelMA) hydrogel to prepare the upper hydrogel, whereas the bottom hydrogel was designed as a double-network hydrogel system, consisting of two interpenetrating polymer networks composed of GelMA, PEGDA, and ß-TCP nanocrystals. The magnesium ion modification process was developed to enhance BP nanosheet stability and provide a sustained release platform for bioactive ions. Our results demonstrated that the upper layer of hydrogel provided a bionic periosteal structure, which significantly facilitated angiogenesis via induction of endothelial cell migration and presented multiple advantages for the upregulation of nerve-related protein expression in neural stem cells (NSCs). Moreover, the bottom layer of the hydrogel significantly promoted bone marrow mesenchymal stem cells (BMSCs) activity and osteogenic differentiation. We next employed the bilayer hydrogel structure to correct rat skull defects. Based on our radiological and histological examinations, the bilayer hydrogel scaffolds markedly enhanced early vascularization and neurogenesis, which prompted eventual bone regeneration and remodeling. Our current strategy paves way for designing nerve-vascular network biomaterials for bone regeneration.

8.
BMC Musculoskelet Disord ; 23(1): 350, 2022 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-35410232

RESUMEN

BACKGROUND: We aimed to compare the intraoperative and early postoperative clinical outcomes of using an acromioclavicular joint hook plate (AJHP) versus a locking plate (LP) in the treatment of anterior sternoclavicular joint dislocation. METHODS: Seventeen patients with anterior sternoclavicular joint dislocation were retrospectively analyzed from May 2014 to September 2019. Six patients were surgically treated with an AJHP, and 11 were surgically treated with an LP. Five male and one female patients composed the AJHP group, and nine male and two female patients composed the LP group. The mean age of all patients was 49.5 years. RESULTS: Reduction and fixation were performed with AJHP or LP in all 17 patients. The mean operative blood loss, operative time, and length of incision in the AJHP group were significantly better than those in the LP group. Shoulder girdle movement of the AJHP group was significantly better than that of the LP group. CONCLUSIONS: This study revealed that AJHP facilitated glenohumeral joint motion, reduced the risk of rupture of mediastinal structures, required a shorter incision, and had lesser blood loss and a shorter duration of operation compared with LP. However, some deficiencies require further improvement.


Asunto(s)
Articulación Acromioclavicular , Luxaciones Articulares , Luxación del Hombro , Articulación Esternoclavicular , Traumatismos Torácicos , Articulación Acromioclavicular/diagnóstico por imagen , Articulación Acromioclavicular/cirugía , Femenino , Humanos , Luxaciones Articulares/diagnóstico por imagen , Luxaciones Articulares/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Luxación del Hombro/cirugía , Articulación Esternoclavicular/diagnóstico por imagen , Articulación Esternoclavicular/cirugía , Resultado del Tratamiento
9.
Adv Healthc Mater ; 11(12): e2102791, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35182097

RESUMEN

Cutaneous wound healing, especially diabetic wound healing, is a common clinical challenge. Reactive oxygen species (ROS) and bacterial infection are two major detrimental states that induce oxidative stress and inflammatory responses and impede angiogenesis and wound healing. A derivative of the metabolite itaconate, 4-octyl itaconate (4OI) has attracted increasing research interest in recent years due to its antioxidant and anti-inflammatory properties. In this study, 4OI-modified black phosphorus (BP) nanosheets are incorporated into a photosensitive, multifunctional gelatin methacrylamide hydrogel to produce a new photothermal therapy (PTT) and photodynamic therapy (PDT) system with antibacterial and antioxidant properties for diabetic wound regeneration. Under laser irradiation, the 4OI-BP-entrapped hydrogel enables rapid gelation, forming a membrane on wounds, and offers high PTT and PDT efficacy to eliminate bacterial infection. Without laser irradiation, BP acts as a carrier and controls the release of 4OI, with which it synergistically enhances antioxidant activity, thus alleviating excessive ROS damage to endothelial cells, promoting neovascularization, and facilitating faster diabetic wound closure. These findings indicate that 4OI-BP-entrapped multifunctional hydrogel provides a stepwise countermeasure with antibacterial and antioxidant properties for enhanced diabetic wound healing and may lead to novel therapeutic interventions for diabetic ulcers.


Asunto(s)
Infecciones Bacterianas , Diabetes Mellitus , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antioxidantes/farmacología , Infecciones Bacterianas/tratamiento farmacológico , Diabetes Mellitus/tratamiento farmacológico , Células Endoteliales , Humanos , Hidrogeles/farmacología , Hidrogeles/uso terapéutico , Fósforo , Especies Reactivas de Oxígeno , Cicatrización de Heridas
10.
Adv Healthc Mater ; 11(6): e2101911, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34865322

RESUMEN

Natural bone is a highly vascularized tissue that relies on the vasculature for blood and nutrients supply to maintain skeletal integrity. Bioactive nanomaterials with the capability of improving vascularized bone regeneration are highly demanded for bone tissue engineering. In this work, 2D silicon phosphorus (SiP) is explored as a new kind of bioactive and biodegradable nanomaterial with excellent angiogenesis and osteogenesis, and a 3D printed biohybrid hydrogel of GelMA-PEGDA incorporated with photocrosslinkable SiP-nanosheet (GelMA-PEGDA/SiPAC) is developed to apply on bone tissue engineering. Findings show that the GelMA-PEGDA/SiPAC possessess excellent biocompatibility and biodegradability, and can sustainably release Si and P elements. Compared with the biohybrid hydrogel scaffolds incorporated with black phosphorus nanosheets, the GelMA-PEGDA/SiPAC can further enhance the osteogenesis of mesenchymal stem cells, and tubular networking of human umbilical vascular endothelial cells. In a rat calvarial bone defect model, the superior angiogenesis and osteogenesis induced by GelMA-PEGDA/SiPAC have been confirmed in vivo. The current strategy paves a new way to design a multifunctional SiP nanocomposite scaffold on mediating the osteogenesis and angiogenesis in one system, and provides a bioactive and biodegradable alternative nanomaterial for tissue engineering and regenerative medicine.


Asunto(s)
Hidrogeles , Silicio , Animales , Regeneración Ósea , Células Endoteliales , Hidrogeles/farmacología , Osteogénesis , Fósforo , Ratas , Ingeniería de Tejidos , Andamios del Tejido
11.
J Healthc Eng ; 2021: 4562618, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34630987

RESUMEN

Background: The treatment of C1-C2 fractures mainly depends on fracture type and the stability of the atlantoaxial joint. Disruption of the C1-C2 combination is a big challenge, especially in avoiding vertebral artery, nerve, and vein sinus injury during the operation. Purpose: This study aims to show the benefit of using the posterior approach and pedicle screw insertion by nailing technique and direct visualization to treat unstable C1-C2 and, moreover, to determine the advantages of performing early MRI in patients with limited neck movement after trauma. Method: Between Jan 2017-Feb 2019, we present 21 trauma patients who suffered from C1, C2, or unstable atlantoaxial joint. X-ray, computed tomography (CT), and magnetic resonance image (MRI) were performed preoperatively. All the patients underwent our surgical procedure (posterior approach and pedicle screw placement by direct visualization and nailing technique). Result: The mean age was 41.1 years old, 8 females and 14 males. The average follow-up time was 2.6 years. Four patients were with C1 fracture, seven with C2 fracture, six with atlantoaxial dislocation, and four with C1 and C2 fractures. The time of MRI was between 12 hours and 48 hours; neck movement symptoms appeared between 2 days and 2 weeks. Conclusion: The posterior approach to treat the C1 and C2 fractures or dislocation by direct visualization and nailing technique can reduce the risk of the vertebral artery, vein sinus, and nerve root injuries with significant improvement. It can show a better angle view while inserting the pedicle screws. An early MRI (12-48 hours) is essential even if no symptoms appear at the time of admission, and if it is normal, it is necessary to repeat it. The presence of skull bleeding can be associated with upper neck instability.


Asunto(s)
Articulación Atlantoaxoidea , Médula Cervical , Fijación Intramedular de Fracturas , Tornillos Pediculares , Adulto , Articulación Atlantoaxoidea/diagnóstico por imagen , Articulación Atlantoaxoidea/cirugía , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino
12.
J Healthc Eng ; 2021: 4798927, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34512936

RESUMEN

It is difficult to assess and monitor the spinal cord injury (SCI) because of its pathophysiology after injury, with different degrees of prognosis and various treatment methods, including laminectomy, durotomy, and myelotomy. Medical communication services with different factors such as time of surgical intervention, procedure choice, spinal cord perfusion pressure (SCPP), and intraspinal pressure (ISP) contribute a significant role in improving neurological outcomes. This review aims to show the benefits of communication services and factors such as ISP, SCPP, and surgical intervention time in order to achieve positive long-term outcomes after an appropriate treatment method in SCI patients. The SCPP was found between 90 and 100 mmHg for the best outcome, MAP was found between 110 and 130 mmHg, and mean ISP is ≤20 mmHg after injury. Laminectomy alone cannot reduce the pressure between the dura and swollen cord. Durotomy and duroplasty considered as treatment choices after severe traumatic spinal cord injury (TSCI).


Asunto(s)
Presión del Líquido Cefalorraquídeo , Traumatismos de la Médula Espinal , Comunicación , Humanos , Laminectomía , Traumatismos de la Médula Espinal/terapia
13.
Oxid Med Cell Longev ; 2021: 9674809, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34422211

RESUMEN

Epithelial regeneration is an essential wound healing process, and recent work suggests that different types of exosomes (Exos) can improve wound repair outcomes by promoting such epithelial regeneration. Platelet-rich plasma (PRP) is known to facilitate enhanced wound healing, yet the mechanisms underlying its activity are poorly understood. To explore these mechanisms, we first isolated PRP-derived Exos (PRP-Exos). Using immortalized keratinocytes (HaCaT cells) treated with PBS, PRP, or PRP-Exos, we conducted a series of in vitro Cell Counting Kit-8 (CCK-8), EdU, scratch wound, and transwell assays. We then established a wound defect model in vivo in mice and assessed differences in the mRNA expression within these wounds to better understand the basis for PRP-mediated wound healing. The functions of PRP-Exos and USP15 in the context of wound healing were then confirmed through additional in vitro and in vivo experiments. We found that PRP-Exos effectively promoted the in vitro proliferation, migration, and wound healing activity of HaCaT cells. USP15 was further identified as a key mediator through which these PRP-Exos were able to promote tissue repair both in vitro and in vivo. At a mechanistic level, USP15 enhanced the functional properties of HaCaT cells by promoting EIF4A1 deubiquitination. Thus, PRP-Exos and USP15 represent promising tools that can promote wound healing via enhancing epithelial regeneration.


Asunto(s)
Factor 4A Eucariótico de Iniciación/metabolismo , Exosomas/metabolismo , Queratinocitos/fisiología , Plasma Rico en Plaquetas/química , Proteasas Ubiquitina-Específicas/metabolismo , Ubiquitinación , Cicatrización de Heridas , Animales , Movimiento Celular , Proliferación Celular , Factor 4A Eucariótico de Iniciación/genética , Exosomas/genética , Humanos , Queratinocitos/citología , Masculino , Ratones , Ratones Endogámicos C57BL , Proteasas Ubiquitina-Específicas/genética
14.
BMC Musculoskelet Disord ; 22(1): 203, 2021 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-33602187

RESUMEN

BACKGROUND: The surgical treatment of acetabular fracture has adverse outcomes and high risk, and minimally invasive method is a good way to reduce complications and improve hip joint function. This study is to investigate the treatment of certain acetabular fractures primarily involving the anterior column and quadrilateral plate using a limited pararectus approach and the anatomical plates. METHODS: A consecutive cohort of 17 patients with anterior displaced acetabular fractures were managed operatively with a limited approach and the anatomical plates. Ten patients had anterior column fractures, 1 patient had anterior wall fracture, 4 patients had transverse fractures and 2 patients had anterior column with posterior hemi-transverse fractures. The inferior half of the pararectus approach was adopted to open the medial window and to access the anterior column and the quadrilateral plate. The anatomical plates were used for internal fixation. Residual displacements were assessed on the postoperative CT scans using a standardized digital method. The surgical details, hip functional outcomes, and complications were noted. RESULTS: All of the patients were operated using the limited pararectus approach and the anatomical plates successfully. The mean operative time and blood loss were 90.9 min and 334.1 ml, respectively. The average postoperative residual gap and step displacement on CT were 2.9 mm and 0.7 mm, respectively. The radiological outcome was estimated according to the Matta score, ten of the cases were graded anatomical, six were graded imperfect, and one was graded poor. Follow up averaged 15 months. Functional outcomes were excellent for nine, good for six, and fair for two. It was noted that one case of peritoneal injury was repaired intraoperatively. CONCLUSIONS: The limited pararectus approach with the advantages of less trauma, direct exposure to the anterior column and quadrilateral plate. The anatomical plates can fit with the surface of the acetabulum, which saves the time of remodeling plates during operation and facilitate fracture reduction. The combination approach can be a good choice for limited surgery of displaced anterior acetabular fractures especially involving the quadrilateral plate.


Asunto(s)
Fracturas Óseas , Fracturas de Cadera , Fracturas de la Columna Vertebral , Acetábulo/diagnóstico por imagen , Acetábulo/lesiones , Acetábulo/cirugía , Placas Óseas , Fijación Interna de Fracturas , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/cirugía , Humanos , Resultado del Tratamiento
15.
Int J Nanomedicine ; 15: 8465-8478, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33149587

RESUMEN

INTRODUCTION: Decellularized matrix from porcine small intestinal submucosa (SIS) endows scaffolds with an ECM-like surface, which enhances stem cell self-renewal, proliferation, and differentiation. Mesoporous bioactive glass (MBG) is extensively recognized as an excellent bio-ceramic for fabricating bone grafts. MATERIALS AND METHODS: In the current study, SIS was doped on an MBG scaffold (MBG/SIS) using polyurethane foam templating and polydopamine chemistry method. To mimic the bony environment of a natural bone matrix, an ECM-inspired delivery system was constructed by coupling the BMP2-related peptide P28 to a heparinized MBG/SIS scaffold (MBG/SIS-H-P28). The release of P28 from MBG/SIS-H-P28 and its effects on the proliferation, viability, and osteogenic differentiation of bone marrow stromal stem cells were investigated in vitro and in vivo. RESULTS: Our research indicated that the novel tissue-derived ECM scaffold MBG/SIS has a hierarchical and interconnected porous architecture, and superior biomechanical properties. MBG/SIS-H-P28 released P28 in a controlled manner, with the long-term release time of 40 d. The results of in vitro experiments showed improvements in cell proliferation, cell viability, alkaline phosphatase activity, and mRNA expression levels of osteogenesis-related genes (Runx-2, OCN, OPN, and ALP) compared to those of MBG/SIS or MBG/SIS-P28 and MBG/SIS-H-P28. The in vivo results demonstrated that MBG/SIS-H-P28 scaffolds evidently increased bone formation in rat calvarial critical-sized defect compared to that in controls. CONCLUSION: MBG/SIS-H-P28 scaffolds show potential as ideal platforms for delivery of P28 and for providing a bony environment for bone regeneration.


Asunto(s)
Ácido Aspártico/química , Materiales Biocompatibles/farmacología , Proteína Morfogenética Ósea 2/farmacología , Huesos/efectos de los fármacos , Cerámica/farmacología , Matriz Extracelular/metabolismo , Osteoblastos/efectos de los fármacos , Péptidos/farmacología , Factor de Crecimiento Transformador beta/farmacología , Animales , Regeneración Ósea/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Línea Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Cinética , Masculino , Ratones , Osteogénesis/efectos de los fármacos , Osteogénesis/genética , Porosidad , Ratas Sprague-Dawley , Proteínas Recombinantes/farmacología , Porcinos , Andamios del Tejido/química
16.
J Cell Mol Med ; 24(23): 13789-13803, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33142041

RESUMEN

Diabetic foot ulcer (DFU) is one of the common ailments of elderly people suffering from diabetes. Exosomes containing various active regulators have been found to play a significant role in apoptosis, cell proliferation and other biological processes. However, the effect and the underlying mechanism of action of diabetes patients derived from circulating exosomes (Dia-Exos) on DFU remain unclear. Herein, we aim to explore the potential regulatory role of Dia-Exos. First, we attempted to demonstrate the harmful effect of Dia-Exos both in vivo and in vitro. miRNA-24-3p (miR-24-3p) was found enriched with Dia-Exos. Hence, inhibition of this miRNA could partially reverse the negative effect of Dia-Exos, thus, in ture, accelerates wound repair. Luciferase assay further verified the binding of miR-24-3p to the 3'-UTR of phosphatidylinositol 3-kinase regulatory subunit gamma (PIK3R3) mRNA and the PIK3R3 expression enhanced human umbilical vein endothelial cells functionality in vitro. Hence, the findings of this study reveal the regulatory role of Dia-Exos in the process of wound healing and provide experimental evidence for the therapeutic effects of knocking down miR-24-3p in DFU treatment.


Asunto(s)
Exosomas/metabolismo , MicroARNs/genética , Neovascularización Fisiológica/genética , Fosfatidilinositol 3-Quinasas/genética , Interferencia de ARN , Cicatrización de Heridas/genética , Animales , Diabetes Mellitus , Exosomas/ultraestructura , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Regulación de la Expresión Génica , Técnicas de Silenciamiento del Gen , Células Endoteliales de la Vena Umbilical Humana , Humanos , Masculino , Ratones , MicroARNs/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo
17.
Aging (Albany NY) ; 12(14): 14978-14989, 2020 07 03.
Artículo en Inglés | MEDLINE | ID: mdl-32620711

RESUMEN

Diabetic foot ulcer (DFU) is a major complication of diabetes in the elderly population. The aim of this study was to investigate the potential mechanism of DFU at the molecular level and explore a feasible therapy for it. Using data from the Gene Expression Omnibus (GEO) database, we found that phosphatase and tensin homolog (PTEN) is differentially expressed between diabetic patients and those without diabetes. We also found that PTEN expression is regulated by glucose stimulation. In addition, decreased function of human umbilical vein endothelial cells (HUVECs) was found to be associated with reduction of PTEN. We identified microRNA-152-3p (miR-152-3p) to be a putative upstream negative regulator of PTEN, and in vivo and in vitro results indicated that miR-152-3p antagonist could restore HUVEC function and accelerate wound repair. Thus, miR-152-3p-induced downregulation of PTEN appears responsible for the delayed wound healing in DFU, and miR-152-3p inhibition may effectively accelerate wound repair, thereby providing a potential target for DFU therapy.


Asunto(s)
Pie Diabético , MicroARNs , Fosfohidrolasa PTEN/metabolismo , Cicatrización de Heridas , Pie Diabético/metabolismo , Pie Diabético/terapia , Descubrimiento de Drogas , Regulación de la Expresión Génica , Células Endoteliales de la Vena Umbilical Humana , Humanos , MicroARNs/antagonistas & inhibidores , MicroARNs/metabolismo , Transducción de Señal , Cicatrización de Heridas/efectos de los fármacos , Cicatrización de Heridas/genética
18.
Chin J Traumatol ; 23(4): 196-201, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32674856

RESUMEN

Outbreak of COVID-19 is ongoing all over the world. Spine trauma is one of the most common types of trauma and will probably be encountered during the fight against COVID-19 and resumption of work and production. Patients with unstable spine fractures or continuous deterioration of neurological function require emergency surgery. The COVID-19 epidemic has brought tremendous challenges to the diagnosis and treatment of such patients. To coordinate the diagnosis and treatment of infectious disease prevention and spine trauma so as to formulate a rigorous diagnosis and treatment plan and to reduce the disability and mortality of the disease, multidisciplinary collaboration is needed. This expert consensus is formulated in order to (1) prevent and control the epidemic, (2) diagnose and treat patients with spine trauma reasonably, and (3) reduce the risk of cross-infection between patients and medical personnel during the treatment.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/epidemiología , Neumonía Viral/epidemiología , Guías de Práctica Clínica como Asunto , Traumatismos Vertebrales/diagnóstico , Traumatismos Vertebrales/terapia , COVID-19 , Infecciones por Coronavirus/prevención & control , Infección Hospitalaria/prevención & control , Servicio de Urgencia en Hospital , Humanos , Pandemias/prevención & control , Grupo de Atención al Paciente , Neumonía Viral/prevención & control , SARS-CoV-2 , Transporte de Pacientes
19.
RSC Adv ; 10(12): 7289-7300, 2020 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-35493905

RESUMEN

Bone morphogenetic protein 2 (BMP-2) is one of the most important factors for bone tissue formation. However, its use over the past decade has been associated with numerous side effects. This is due to the fact that recombinant human (rh) BMP-2 has several biological functions, as well as that non-physiological high dosages were commonly administered. In this study, we synthesized a novel BMP-2-related peptide (designated P28) and fused a mutant domain in placenta growth factor-2 (PlGF-2123-144*) that allowed for the "super-affinity" of extracellular matrix proteins to P28, effectively controlling the release of low dosage P28 from small intestinal submucosa/polylactic acid (SIS/PLA) scaffolds. These have been shown to be excellent scaffold materials both in vivo and in vitro. The aim of this study was to determine whether these scaffolds could support the controlled release of P28 over time, and whether the composite materials could serve as structurally and functionally superior bone substitutes in vivo. Our results demonstrated that P28 could be released slowly from SIS/PLA to promote the adhesion, proliferation, and differentiation of bone marrow stromal cells (BMSCs) in vitro. In vivo, radiographic and histological examination showed that SIS/PLA/P28/PlGF-2123-144* completely repaired critical-size bone defects, compared to SIS/PLA, SIS/PLA/PlGF-2123-144*, or SIS/PLA/P28 alone. These findings suggest that this controlled release system may have promising clinical applications in bone tissue engineering.

20.
Eur Spine J ; 28(10): 2275-2282, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31440894

RESUMEN

PURPOSE: Treatment options for adult spinal cord injury without radiographic abnormality (ASCIWORA) varied. Compression of ASCIWORA may more likely result from spinal cord lesions such as edema and hemorrhage or contusion. This study aimed to explore the clinical effect of early durotomy with duroplasty decompression in the treatment of severe ASCIWORA. METHODS: Data of 16 patients with ASCIWORA who underwent early ( < 72 h) posterior laminectomy followed by durotomy with duroplasty decompression from June 2015 to January 2017 were retrospectively analyzed. Patients' prognosis was analyzed by American Spinal Injury Association Impairment Scale (AIS) grades and scores. In 3 patients, intraspinal pressure (ISP) was continuously monitored for 1 week. RESULTS: Cervical magnetic resonance imaging (MRI) revealed spinal cord edema in 9 patients and suspected hemorrhage or contusion in 7 cases. Pathological manifestations of spinal cord injury found during the operation were consistent with preoperative MRI findings. Of the 16 cases, AIS grade was improved by 1 grade in 3 cases, 2 grades in 11 cases, and 3 grades in 1 case. The AIS scores at the last follow-up were significantly higher than preoperative scores. There was a high level of ISP after laminectomy, whereas ISP continued to decrease steadily after durotomy. CONCLUSIONS: Durotomy helps thoroughly decompress the spinal cord and improve cerebrospinal fluid circulation in severe ASCIWORA cases. Cervical MRI and pathological investigation of the spinal cord can be used to evaluate and predict the prognosis of ASCIWORA patients. ISP monitoring is an effective method for evaluating intramedullary pressure and decompression. These slides can be retrieved under Electronic Supplementary Material.


Asunto(s)
Descompresión Quirúrgica/métodos , Duramadre/cirugía , Procedimientos Neuroquirúrgicos , Traumatismos de la Médula Espinal/cirugía , Adulto , Anciano , Vértebras Cervicales/diagnóstico por imagen , Femenino , Humanos , Laminectomía , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven
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