RESUMO
Medical silks have captured global interest. While silk sutures have a long track record in humans, silk bioconjugates are still in preclinical development. This perspective examines key advances in silk bioconjugation, including the fabrication of silk-protein conjugates, bioconjugated silk particles, and bioconjugated substrates to enhance cell-material interactions in two and three dimensions. Many of these systems rely on chemical modification of the silk biopolymer, often using carbodiimide and reactive ester chemistries. However, recent progress in enzyme-mediated and click chemistries has expanded the molecular toolbox to enable biorthogonal, site-specific conjugation in a single step when combined with recombinant silk fibroin tagged with noncanonical amino acids. This perspective outlines key strategies available for chemical modification, compares the resulting silk conjugates to clinical benchmarks, and outlines open questions and areas that require more work. Overall, this assessment highlights a domain of new sunrise capabilities and development opportunities for silk bioconjugates that may ultimately offer new ways of delivering improved healthcare.
Assuntos
Seda , Animais , Humanos , Fibroínas , Seda/química , Seda/uso terapêuticoRESUMO
Introduction: The pathogenesis of diabetic nephropathy (DN) is complex, inflammation is the central link among the inducing factors in the existing research, and the gutkidney axis could scientifically explain the reasons for the accumulation of chronic low-grade inflammation. As both a medicine and food, corn silk contains abundant polysaccharides. Historical studies and modern research have both confirmed its intervention effect on diabetes and DN, but the mechanism of action is unclear. Methods: In this study, a DN rat model was generated, and the therapeutic effect of corn silk polysaccharides (CSPs) was evaluated based on behavioral, histopathological and biochemical indicators. We attempted to fully understand the interactions between CSPs, the gut microbiota and the host at the systemic level from a gut microbiota metabolomics perspective to fundamentally elucidate the mechanisms of action that can be used to intervene in DN. Results: Research has found that the metabolic pathways with a strong correlation with CSPs were initially identified as glycerophosphate, fatty acid, bile acid, tyrosine, tryptophan and phenylalanine metabolism and involved Firmicutes, Bacteroides, Lachnospiraceae-NK4A136- group and Dubosiella, suggesting that the effect of CSPs on improving DN is related to changes in metabolite profiles and gut microbiota characteristics. Discussion: CSPs could be harnessed to treat the abnormal metabolism of endogenous substances such as bile acids and uremic toxins caused by changes in gut microbiota, thus alleviating kidney damage caused by inflammation. In view of its natural abundance, corn silk is safe and nontoxic and can be used for the prevention and treatment of diabetes and DN.
Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Microbioma Gastrointestinal , Ratos , Animais , Nefropatias Diabéticas/patologia , Zea mays , Ecossistema , Inflamação , Homeostase , Polissacarídeos/uso terapêutico , Polissacarídeos/farmacologia , Seda/farmacologia , Seda/uso terapêuticoRESUMO
The use of cyanoacrylate tissue adhesive for surgical wound closure has become increasingly popular in recent years and has shown efficacy. Therefore, the aim of this systematic review was to compare the effectiveness of cyanoacrylate adhesive as a substitute for conventional suture placement after extraction of impacted third molars. The PubMed/MEDLINE, Scopus, Cochrane, and gray literature databases were searched for randomized or controlled prospective clinical trials published up to October 2022 that compared the use of cyanoacrylate adhesive and conventional silk suture in third molar surgeries. The risk of bias of each study was assessed using the RoB 2 tool (revised Cochrane risk of bias tool for randomized trials). Five randomized clinical trials with a total of 236 patients were included. The most commonly evaluated outcomes were pain and bleeding. The type of adhesive used varied and included ethyl-2-cyanoacrylate, isoamyl 2-cyanoacrylate, and a mixture of n-butyl cyanoacrylate and 2-octyl cyanoacrylate. Compared with 3-0 silk suture, cyanoacrylate tissue adhesive resulted in lower levels of postoperative pain in 3 studies and lower rates of bleeding in all 5 studies. Thus, cyanoacrylate can be a good substitute for silk sutures for wound closure in intraoral surgeries.
Assuntos
Adesivos Teciduais , Humanos , Adesivos Teciduais/uso terapêutico , Dente Serotino/cirurgia , Estudos Prospectivos , Cianoacrilatos/uso terapêutico , Suturas , Seda/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Silk sutures with antibacterial and anti-inflammatory functions were developed for sustained dual-drug delivery to prevent surgical site infections (SSIs). The silk sutures were prepared with core-shell structures braided from degummed silk filaments and then coated with a silk fibroin (SF) layer loaded with berberine (BB) and artemisinin (ART). Both the rapid release of drugs to prevent initial biofilm formation and the following sustained release to maintain effective concentrations for more than 42 days were demonstrated. In vitro assays using human fibroblasts (Hs 865.Sk) demonstrated cell proliferation on the materials, and hemolysis was 2.4 ± 0.8%, lower than that required by ISO 10993-4 standard. The sutures inhibited platelet adhesion and promoted collagen deposition and blood vessel formation. In vivo assessments using Sprague-Dawley (SD) rats indicated that the coating reduced the expression of pro-inflammatory cytokines interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α), shortening the inflammatory period and promoting angiogenesis. The results demonstrated that these new sutures exhibited stable structures, favorable biocompatibility, and sustainable antibacterial and anti-inflammatory functions with potential for surgical applications.
Assuntos
Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Seda/química , Seda/farmacologia , Infecção da Ferida Cirúrgica/prevenção & controle , Suturas , Animais , Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Artemisininas/química , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Berberina/química , Berberina/farmacologia , Berberina/uso terapêutico , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Materiais Revestidos Biocompatíveis/uso terapêutico , Modelos Animais de Doenças , Liberação Controlada de Fármacos , Quimioterapia Combinada/métodos , Escherichia coli/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Humanos , Masculino , Fenômenos Físicos , Ratos Sprague-Dawley , Seda/uso terapêutico , Staphylococcus aureus/efeitos dos fármacos , Infecção da Ferida Cirúrgica/metabolismo , Infecção da Ferida Cirúrgica/patologiaRESUMO
BACKGROUND: To investigate osteointegration at the graft-bone interface and the prevention of osteoarthritis after anterior cruciate ligament (ACL) reconstruction using a silk-collagen scaffold with both ends modified by hydroxyapatite (HA) in a rabbit model. METHODS: The HA/silk-collagen scaffold was fabricated using a degummed, knitted silk scaffold, collagen I matrix, and simulated body fluid (SBF). The HA/silk-collagen scaffold was rolled up to make a graft for replacing the native ACL in the experimental group (HA group), and the silk-collagen scaffold was used in the control (S group). All specimens were harvested at 16 weeks postoperatively to evaluate graft-bone healing and osteoarthritis prevention. RESULTS: Histological staining revealed the massive formation of more mature bone at the tendon-bone interface, and immunohistochemistry staining revealed more collagen I and osteocalcin deposition in the HA group than in the S group. Higher signals indicating more bone mineral formation were detected in the HA group than in the S group, which was consistent with the results of biomechanical testing. Better osteoarthritis prevention was also observed in the HA group, indicating a more stable knee joint in the HA group than in the S group. CONCLUSION: The HA/silk-collagen scaffold promotes osteointegration at the tendon-bone interface after ACL reconstruction and has great potential for clinical applications.
Assuntos
Reconstrução do Ligamento Cruzado Anterior/métodos , Ligamento Cruzado Anterior/cirurgia , Colágeno/uso terapêutico , Durapatita/uso terapêutico , Seda/uso terapêutico , Animais , Ligamento Cruzado Anterior/fisiopatologia , Reconstrução do Ligamento Cruzado Anterior/efeitos adversos , Fenômenos Biomecânicos , Interface Osso-Implante/fisiopatologia , Modelos Animais de Doenças , Osteoartrite/etiologia , Osteoartrite/prevenção & controle , Osteogênese , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Coelhos , CicatrizaçãoRESUMO
Purpose: The authors compare the outcomes and revision rates for external levator aponeurotic advancement for the treatment of involutional ptosis using non-absorbable silk and absorbable polyglactin sutures.Methods: An IRB-approved retrospective chart review identified 121 patients who underwent external levator advancement for involutional ptosis between 2015 and 2016 by the senior author (JBH). All patients underwent ptosis repair using either 5-0 polyglactin 910 on a S-14 spatulated needle or 6-0 silk on a G-1 reverse cutting needle for the aponeurotic advancement. Ptosis etiologies other than involutional ptosis were excluded. Patients with >0.5 mm of upper lid height asymmetry post-operatively underwent surgical adjustment. Demographics, clinical findings and revision rates were collected and analyzed from follow-up visits.Results: 116 patients (190 eyelids) met inclusion criteria. Fewer ptosis repairs performed using silk sutures necessitated adjustment when compared to those using polyglactin (1/73 [1.4%] vs. 14/117 [12.0%], p = 0.010). Silk direct connection sutures had no better stability than polyglactin direct connection sutures (p = 0.16), but silk hang-back sutures were significantly superior to polyglactin hang-back sutures (p = 0.035). Thirteen out of fifteen (86.7%) revisions were advancements to raise the eyelid, while two (13.3%) were recessions.Conclusion: Non-absorbable silk suture may be superior to absorbable polyglactin, necessitating fewer surgical revisions. Silk demonstrated superiority to polyglactin when a hang-back suture was employed. Since the need to place direct or hang-back sutures cannot be made pre-operatively, the authors modified their technique to utilize silk sutures for external aponeurotic ptosis repair.
Assuntos
Blefaroplastia/métodos , Blefaroptose/diagnóstico , Blefaroptose/cirurgia , Poliglactina 910/uso terapêutico , Seda/uso terapêutico , Suturas , Adulto , Blefaroplastia/efeitos adversos , Estudos de Coortes , Estética , Pálpebras/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Reoperação , Estudos Retrospectivos , Índice de Gravidade de Doença , Técnicas de Sutura , Resultado do TratamentoRESUMO
Large, superficial burn wounds require many painful dressing changes and, thus, dressings that can stay on the wound and peel off during re-epithelization such as Biobrane® and Suprathel® are preferred, but they are costly. Natural silk has shown good outcomes with respect to wound healing, scarring, and patient satisfaction. This study aimed to evaluate the efficacy of natural silk compared with that of initially used dressings for the treatment of superficial burn wounds greater than 10% of the TBSA. Patients with superficial burns covering >10% of the TBSA were treated with pure silk for the first time (treatment group). Complications during wound healing with respect to the need for further surgery and scarring were compared with those of patients with similar burns of more than 10% TBSA and treated with nylon mesh and collagen instead of silk (treatment group). The treatment and control group comprised 25 and 13 patients, respectively. In total, 88% of patients in the treatment group did not require further treatment, while two patients with chemical burns needed further surgeries. Moreover, patients reported high satisfaction with respect to scarring and aesthetic outcome. Meanwhile, 85% of patients in the control group healed without further surgery and showed higher median hypopigmentation and hyperpigmentation after 12 months. Silk is an effective wound dressing for the treatment of large superficial burn wounds. It avoids painful dressing changes and yields satisfactory aesthetic outcomes. However, especially in large burns, careful initial wound depth assessment is crucial to prevent infection and reoperations.
Assuntos
Bandagens , Queimaduras/terapia , Seda/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Queimaduras/complicações , Queimaduras/patologia , Cicatriz/etiologia , Cicatriz/patologia , Cicatriz/prevenção & controle , Estudos de Viabilidade , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Retrospectivos , Resultado do Tratamento , Cicatrização , Adulto JovemRESUMO
BACKGROUND The study aimed to develop a novel orthopedic surgical scaffold made of collagen and silk to repair the tendon and bone interface, and to investigate its influence on tendon and bone healing in a rabbit model. MATERIAL AND METHODS Four types of surgical scaffold were prepared, including a random collagen scaffold (RCS), an aligned collagen scaffold (ACS), a random collagen scaffold combined with knitted silk (RCSS), and an aligned collagen scaffold combined with knitted silk (ACSS). Rabbit bone marrow stem cells (BMSCs) were cultured and seeded onto the RCS and ACS scaffold. The animal model included four-month-old female New Zealand White rabbits (N=20) that underwent drilling into the rotator cuff of the left supraspinatus muscle tendon, randomized into the ACSS and RCSS groups. RESULTS Rabbit BMSCs adhered to and proliferated on the RCS and ACS in vitro. Transcription levels of the COL I, COL III, and tenascin (TCN) genes were significantly increased in the ACS group compared with the RCS group. Transcription levels of COL I, runt-related transcription factor-2 (RUNX-2) and bone morphogenetic protein-2 (BMP-2) were significantly increased in the RCS group compared with the ACS group. RCSS and ACSS implanted in the rabbit models for eight weeks resulted in more regenerative tissue in the RCSS group compared with the ACSS group, with new cartilage at the tendon and bone interface at 12 weeks. CONCLUSIONS A collagen and silk scaffold improved healing of the tendon and bone interface in a rabbit model.
Assuntos
Procedimentos Ortopédicos/métodos , Alicerces Teciduais/química , Cicatrização/fisiologia , Animais , Células da Medula Óssea/metabolismo , Proteína Morfogenética Óssea 2/genética , Osso e Ossos/cirurgia , Colágeno/química , Colágeno/uso terapêutico , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Modelos Animais de Doenças , Feminino , Coelhos , Manguito Rotador/cirurgia , Seda/química , Seda/uso terapêutico , Células-Tronco/metabolismo , Tenascina/genética , Tendões/cirurgiaRESUMO
Stroke, traumatic brain injuries, and other similar conditions often lead to significant loss of functional brain tissue and associated disruption of neuronal signaling. A common strategy for replacing lost neurons is the injection of dissociated neural stem cells or differentiated neurons. However, this method is unlikely to be suitable for replacing large brain cavities, and the resulting distribution of neurons may lack the necessary architecture to support appropriate brain function. Engineered neural tissues may be a viable alternative. Cell death is a prominent concern in neuronal grafting studies, a problem that could be magnified with the transplantation of engineered neural tissues. Here, we examined the effect of one contributor to cell death, acute cerebral inflammation, on neuronal survival after the transplantation of bioengineered constructs based on silk scaffolds. We found evidence of a high degree of inflammation and poor neuronal survival after introducing engineered constructs into the motor cortex of rats. Integrating a corticosteroid (methylprednisolone) into the constructs resulted in significantly improved neuron survival during the acute phase of inflammation. The improved construct survival was associated with decreased markers of inflammation and an anti-inflammatory state of the immune system due to the steroid treatment.
Assuntos
Transplante de Tecido Encefálico/métodos , Inflamação/prevenção & controle , Seda/química , Alicerces Teciduais/química , Animais , Bombyx , Encéfalo/citologia , Transplante de Tecido Encefálico/efeitos adversos , Sobrevivência Celular , Células Cultivadas , Inflamação/etiologia , Masculino , Neurônios/citologia , Ratos , Ratos Sprague-Dawley , Seda/uso terapêutico , Engenharia TecidualRESUMO
Anterior cruciate ligament (ACL) reconstruction is the leading treatment for ACL rupture. Ligament Advanced Reinforcement System (LARS), which is made of polyethylene terephthalate (PET), is the most frequently used artificial ligament for ACL reconstruction. However, PET is hydrophobic, so it is difficult to induce the ingrowth of the autologous tissue. The aim of this study is to explore the effects of silk hybrid on the ligamentization of the PET artificial ligament in a canine ACL reconstruction model. Silk/PET hybrid suspensory ligament was fabricated with silk in the weft yarn and PET in the warp yarn, while PET suspensory ligament was fabricated with PET in both the weft and warp yarns. After fabrication, the micromorphology of the ligaments was observed and mechanical testing was performed. Though the failure loads of the degummed silk/PET hybrid suspensory ligaments were significantly lower than those of the PET suspensory ligaments (P < 0.001), both of them were enough for ACL reconstructions of beagle dogs. In the animal study, 14 beagle dogs were divided into PET suspensory ligament group and silk/PET hybrid suspensory ligament group randomly, with 7 dogs in each. The dogs underwent ACL reconstructions in their right knees. At postoperative 6 months, the dogs were sacrificed, and the specimens were evaluated with gross observation, histology, immunohistochemistry, and mechanical testing. The histological and immunohistochemical results showed that the native ACL of the beagle dog held abundant fibroblasts and collagen. The PET-regenerated ligament was loose, and there was a small amount of autologous tissue and collagen. Compared to the PET-regenerated ligament, the silk/PET hybrid-regenerated ligament had a compact structure, and there was more regenerated autologous tissue and collagen. In conclusion, compared to the PET ligament, the silk/PET hybrid ligament kept greater ability to induce the ingrowth of the autologous tissue, indicating that the silk hybrid had enhanced the ligamentization of the PET artificial ligament.
Assuntos
Lesões do Ligamento Cruzado Anterior/terapia , Reconstrução do Ligamento Cruzado Anterior/métodos , Materiais Biocompatíveis/uso terapêutico , Polietilenotereftalatos/uso terapêutico , Seda/uso terapêutico , Alicerces Teciduais , Animais , Ligamento Cruzado Anterior/fisiologia , Materiais Biocompatíveis/química , Bombyx/química , Cães , Feminino , Polietilenotereftalatos/química , Regeneração , Seda/química , Alicerces Teciduais/químicaRESUMO
The aim of the present article was to study the healing of wounds using spider silk. Eight New Zealand female rabbits were selected as animal model. First, 3 identical wounds with length of 15 mm and a depth of 4 mm on the back of each rabbit were created. The first group, as standard control, did not receive any special treatment, they were treated only with saline and Vaseline locally. The second group, as positive control, received a thin film of phenytoin 1% ointment locally. The third group, as treated group, received a thin film of spider silk protein. At the end of the study, a biopsy of skin was done. After tissue preparation, all sections were evaluated. Some morphometrical parameters such as counting cells, fibroblasts, blood vessels, determination of the area of the wound closure, necrotic tissue, speed of wound healing, and epidermal thickness were done, and for data statistical analysis, SPSS software and Excel software were used. The results of this study showed that spider silk dressing may benefit as a possible effect of nanoparticles in the test preparation in wound healing.
Assuntos
Curativos Biológicos , Seda/uso terapêutico , Aranhas , Cicatrização/fisiologia , Ferimentos e Lesões/terapia , Animais , Modelos Animais de Doenças , Proteínas de Insetos/uso terapêutico , Coelhos , Resultado do TratamentoRESUMO
The osteochondral defect (OD) comprises the articular cartilage and its subchondral bone. The treatment of these lesions remains as one of the most problematic clinical issues, since these defects include different tissues, requiring distinct healing approaches. Among the growing applications of regenerative medicine, clinical articular cartilage repair has been used for two decades, and it is an effective example of translational medicine; one of the most used cell-based repair strategies includes implantation of autologous cells in degradable scaffolds such as alginate, agarose, collagen, chitosan, chondroitin sulfate, cellulose, silk fibroin, hyaluronic acid, and gelatin, among others. Concerning the repair of osteochondral defects, tissue engineering and regenerative medicine started to design single- or bi-phased scaffold constructs, often containing hydroxyapatite-collagen composites, usually used as a bone substitute. Biomolecules such as natural and synthetic have been explored to recreate the cartilage-bone interface through multilayered biomimetic scaffolds. In this chapter, a succinct description about the most relevant natural and synthetic biomolecules used on cartilage and bone repair, describing the procedures to obtain these biomolecules, their chemical structure, common modifications to improve its characteristics, and also their application in the biomedical fields, is given.
Assuntos
Materiais Biocompatíveis/uso terapêutico , Fatores Biológicos/uso terapêutico , Produtos Biológicos/uso terapêutico , Materiais Biomiméticos/uso terapêutico , Doenças Ósseas/terapia , Doenças das Cartilagens/terapia , Medicina Regenerativa/métodos , Engenharia Tecidual/métodos , Animais , Terapia Biológica/métodos , Configuração de Carboidratos , Cartilagem Articular/lesões , Previsões , Humanos , Polímeros/síntese química , Polímeros/uso terapêutico , Polissacarídeos/uso terapêutico , Seda/uso terapêutico , Terapias em Estudo , Alicerces TeciduaisRESUMO
Timely and spatially-regulated injectable hydrogels, able to suppress growing tumors in response to conformational transitions of proteins, are of great interest in cancer research and treatment. Herein, we report rapidly responsive silk fibroin (SF) hydrogels formed by a horseradish peroxidase (HRP) crosslinking reaction at physiological conditions, and demonstrate their use as an artificial biomimetic three-dimensional (3D) matrix. The proposed SF hydrogels presented a viscoelastic nature of injectable hydrogels and spontaneous conformational changes from random coil to ß-sheet conformation under physiological conditions. A human neuronal glioblastoma (U251) cell line was used for screening cell encapsulation and in vitro evaluation within the SF hydrogels. The transparent random coil SF hydrogels promoted cell viability and proliferation up to 10 days of culturing, while the crystalline SF hydrogels converted into ß-sheet structure induced the formation of TUNEL-positive apoptotic cells. Therefore, this work provides a powerful tool for the investigation of the microenvironment on the programed tumor cells death, by using rapidly responsive SF hydrogels as 3D in vitro tumor models.
Assuntos
Antineoplásicos/uso terapêutico , Fibroínas/uso terapêutico , Hidrogéis/uso terapêutico , Seda/uso terapêutico , Microambiente Tumoral/efeitos dos fármacos , Apoptose , Linhagem Celular , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , HumanosRESUMO
BACKGROUND: The long-term aesthetic appearance of scars is of great importance to patients. Biobrane (Smith and Nephew, Fort Worth, Texas), a biosynthetic skin dressing, is a successfully established dressing for the treatment of superficial wounds. A new silk barrier dressing (Dressilk; Prevor, Moulin de Verville, France) has also shown good results in wound healing. This study evaluated the long-term scar quality of superficial wounds treated with these dressings. METHODS: From February 2012 to May 2013, 11 patients with burns in need of skin grafting received donor site treatment. Study authors dressed 2 adjacent, standardized, partial-thickness skin graft donor sites on each participant with Biobrane or Dressilk. Scar formation on both treated areas was compared 24 months after initial application using subjective and objective assessment methods. RESULTS: Independent of treatment, the majority of the patients described scar quality similar to normal skin using subjective and objective evaluation tools. However, for scar perfusion, significantly lower oxygen saturation was shown in both treated areas compared with untreated skin. CONCLUSIONS: Comparatively, the 2 wound dressings showed similar results, making silk dressings an interesting alternative to biosynthetic ones.
Assuntos
Queimaduras/cirurgia , Cicatriz/prevenção & controle , Materiais Revestidos Biocompatíveis/uso terapêutico , Seda/uso terapêutico , Transplante de Pele/métodos , Adulto , Curativos Biológicos , Queimaduras/complicações , Cicatriz/etiologia , Estudos de Coortes , Estética , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Transplante de Pele/efeitos adversos , Resultado do Tratamento , Cicatrização/fisiologiaRESUMO
The role of biomaterials in tissue engineering and regenerative medicine strategies to treat vision loss associated with damage to tissues in the anterior segment of the eye has been studied for several years. This has mostly involved replacement and support for the cornea and conjunctiva. These are complex tissues with specific functional requirements for different parts of the tissue. Amniotic membrane (AM) is used in clinical practice to transplant autologous or allogenic cells to the corneal surface. Fibrin gels have also progressed to clinical use under specific conditions. Alternatives to AM such as collagen gels, other natural materials, for example keratin and silks, and synthetic polymers have received considerable attention in laboratory and animal studies. This experience is building a body of evidence to demonstrate the potential of tissue engineering and regenerative medicine in corneal and conjunctival reconstruction and can also lead to other applications in the anterior segment of the eye, for example, the trabecular meshwork. There is a real clinical need for new procedures to overcome vision loss but there are also opportunities for developments in ocular applications to lead to biomaterials innovations for use in other clinical areas.
Assuntos
Materiais Biocompatíveis , Doenças da Túnica Conjuntiva/terapia , Doenças da Córnea/terapia , Medicina Regenerativa , Âmnio/química , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/uso terapêutico , Colágeno/química , Colágeno/uso terapêutico , Doenças da Túnica Conjuntiva/patologia , Doenças da Córnea/patologia , Humanos , Queratinas/química , Queratinas/uso terapêutico , Seda/uso terapêuticoRESUMO
Recombinant silk-elastinlike protein polymers (SELPs) combine the biocompatibility and thermoresponsiveness of human tropoelastin with the strength of silk. Direct control over structure of these monodisperse polymers allows for precise correlation of structure with function. This work describes the fabrication of the first SELP nanogels and evaluation of their physicochemical properties and thermoresponsiveness. Self-assembly of dilute concentrations of SELPs results in nanogels with enhanced stability over micelles due to physically crosslinked beta-sheet silk segments. The nanogels respond to thermal stimuli via size changes and aggregation. Modifying the ratio and sequence of silk to elastin in the polymer backbone results in alterations in critical gel formation concentration, stability, aggregation, size contraction temperature, and thermal reversibility. The nanogels sequester hydrophobic compounds and show promise in delivery of bioactive agents.
Assuntos
Sistemas de Liberação de Medicamentos , Elastina/química , Polietilenoglicóis/química , Polietilenoimina/química , Seda/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/uso terapêutico , Elastina/uso terapêutico , Humanos , Nanogéis , Nanopartículas/química , Polietilenoglicóis/uso terapêutico , Polietilenoimina/uso terapêutico , Polímeros/química , Polímeros/uso terapêutico , Agregados Proteicos , Proteínas Recombinantes/química , Proteínas Recombinantes/uso terapêutico , Seda/uso terapêutico , Sensação TérmicaAssuntos
Procedimentos Cirúrgicos Cardíacos/instrumentação , Materiais Revestidos Biocompatíveis , Ciência dos Materiais , Seda , Suturas , Adesivos Teciduais , Animais , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/uso terapêutico , Procedimentos Cirúrgicos Cardíacos/métodos , Materiais Revestidos Biocompatíveis/farmacologia , Materiais Revestidos Biocompatíveis/uso terapêutico , Gastrópodes , Humanos , Ciência dos Materiais/métodos , Ciência dos Materiais/tendências , Teste de Materiais , Seda/farmacologia , Seda/uso terapêutico , Aranhas , Adesivos Teciduais/farmacologia , Adesivos Teciduais/uso terapêuticoRESUMO
In addition to customizing shapes of metal bone substitutes for patients, the 3D printing technique can reduce the modulus of the substitutes through the design and manufacture of interconnected porous structures, achieving the modulus match between substitute and surrounding bone to improve implant longevity. However, the porous bone substitutes take more risks of postoperative infection due to its much larger surface area compared with the traditional casting solid bone substitute. Here, we prepared of gentamicin-loaded silk fibroin coatings on 3D-printed porous cobalt-chromium-molybdenum (CoCrMo) bone substitutes via electrophoretic deposition technique. Through optimization, relatively intact, continuous, homogeneous, and conformal coatings with a thickness of 2.30 ± 0.58 µm were deposited around the struts with few pore blocked. The porous metal structures exhibited no loss in mechanical properties after the anode galvanic corrosion in EPD process. The initial osteoblastic response on coatings was better than that on metal surface, including cell spreading, proliferation and cytotoxicity. Antibacterial efficacy experiments showed that the coatings had an antibacterial effect on both adherent and planktonic bacteria within 1 week. These results suggested that the beneficial properties of anode electrophoretic deposited silk fibroin coatings could be exploited to improve the biological functionality of porous structures made of medical metals.
Assuntos
Substitutos Ósseos/síntese química , Materiais Revestidos Biocompatíveis/síntese química , Eletroforese/métodos , Gentamicinas/síntese química , Próteses e Implantes/microbiologia , Substitutos Ósseos/química , Substitutos Ósseos/uso terapêutico , Cromo/química , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/uso terapêutico , Cobalto/química , Fibroínas/química , Fibroínas/uso terapêutico , Gentamicinas/química , Gentamicinas/uso terapêutico , Humanos , Molibdênio/química , Osteoblastos/efeitos dos fármacos , Osteoblastos/microbiologia , Porosidade , Impressão Tridimensional , Próteses e Implantes/efeitos adversos , Seda/química , Seda/uso terapêutico , Propriedades de SuperfícieRESUMO
Biological self-assembly is a process in which building blocks autonomously organize to form stable supermolecules of higher order and complexity through domination of weak, noncovalent interactions. For silk protein, the effect of high incubating temperature on the induction of secondary structure and self-assembly was well investigated. However, the effect of freezing and thawing on silk solution has not been studied. The present work aimed to investigate a new all-aqueous process to form 3D porous silk fibroin matrices using a freezing-assisted self-assembly method. This study proposes an experimental investigation and optimization of environmental parameters for the self-assembly process such as freezing temperature, thawing process, and concentration of silk solution. The optical images demonstrated the possibility and potential of -80ST48 treatment to initialize the self-assembly of silk fibroin as well as controllably fabricate a porous scaffold. Moreover, the micrograph images illustrate the assembly of silk protein chain in 7 days under the treatment of -80ST48 process. The surface morphology characterization proved that this method could control the pore size of porous scaffolds by control of the concentration of silk solution. The animal test showed the support of silk scaffold for cell adhesion and proliferation, as well as the cell migration process in the 3D implantable scaffold.
Assuntos
Fibroínas/química , Seda/química , Engenharia Tecidual , Alicerces Teciduais/química , Animais , Bombyx/química , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fibroínas/uso terapêutico , Congelamento , Humanos , Estrutura Secundária de Proteína , Seda/uso terapêuticoRESUMO
BACKGROUND: Atopic eczema (AE) is a chronic, itchy, inflammatory skin condition that affects the quality of life of children and their families. The role of specialist clothing in the management of AE is poorly understood. OBJECTIVES: To assess the effectiveness and cost-effectiveness of silk garments for the management of AE in children with moderate to severe disease. DESIGN: Parallel-group, observer-blind, randomised controlled trial of 6 months' duration, followed by a 2-month observational period. A nested qualitative study evaluated the beliefs of trial participants, health-care professionals and health-care commissioners about the use of silk garments for AE. SETTING: Secondary care and the community in five UK centres. PARTICIPANTS: Children aged 1-15 years with moderate or severe AE. INTERVENTIONS: Participants were randomised (1 : 1 using online randomisation) to standard care or standard care plus 100% silk garments made from antimicrobially protected knitted sericin-free silk [DermaSilkTM (AlPreTec Srl, San Donà di Piave, Italy) or DreamSkinTM (DreamSkin Health Ltd, Hatfield, UK)]. Three sets of garments were supplied per participant, to be worn for up to 6 months (day and night). At 6 months the standard care group received the garments to use for the remaining 2-month observational period. MAIN OUTCOME MEASURES: Primary outcome - AE severity using the Eczema Area and Severity Index (EASI) assessed at 2, 4 and 6 months, by nurses blinded to treatment allocation. EASI scores were log-transformed for analysis. Secondary outcomes - patient-reported eczema symptoms (Patient Oriented Eczema Measure); global assessment of severity (Investigator Global Assessment); quality of life of the child (Atopic Dermatitis Quality of Life, Child Health Utility - 9 Dimensions), family (Dermatitis Family Impact Questionnaire) and main carer (EuroQoL-5 Dimensions-3 Levels); use of standard eczema treatments (e.g. emollients, topical corticosteroids); and cost-effectiveness. The acceptability and durability of the clothing, and adherence to wearing the garments, were assessed by parental/carer self-report. Safety outcomes - number of skin infections and hospitalisations for AE. RESULTS: A total of 300 children were randomised (26 November 2013 to 5 May 2015): 42% female, 79% white, mean age 5 years. The primary analysis included 282 out of 300 (94%) children (n = 141 in each group). Garments were worn for at least 50% of the time by 82% of participants. Geometric mean EASI scores at baseline, 2, 4 and 6 months were 8.4, 6.6, 6.0, 5.4 for standard care and 9.2, 6.4, 5.8, 5.4 for silk clothing, respectively. There was no evidence of difference between the groups in EASI score averaged over all follow-up visits adjusted for baseline EASI score, age and centre (ratio of geometric means 0.95, 95% confidence interval 0.85 to 1.07; p = 0.43). This confidence interval is equivalent to a difference of -1.5 to 0.5 in the original EASI scale units. Skin infections occurred in 39 out of 141 (28%) and 36 out of 142 (25%) participants for standard care and silk clothing groups, respectively. The incremental cost per QALY of silk garments for children with moderate to severe eczema was £56,811 from a NHS perspective in the base case. Sensitivity analyses supported the finding that silk garments do not appear to be cost-effective within currently accepted thresholds. LIMITATIONS: Knowledge of treatment allocation may have affected behaviour and outcome reporting for some of the patient-reported outcomes. CONCLUSIONS: The addition of silk garments to standard AE care is unlikely to improve AE severity, or to be cost-effective compared with standard care alone, for children with moderate or severe AE. This trial adds to the evidence base to guide clinical decision-making. FUTURE WORK: Non-pharmacological interventions for the management of AE remain a research priority among patients. TRIAL REGISTRATION: Current Controlled Trials ISRCTN77261365. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 16. See the NIHR Journals Library website for further project information.