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BACKGROUND: Free tissue transfer to cover complex wounds with exposed critical structures results in donor-site morbidity. Perfusion decellularization and recellularization of vascularized composite tissues is an active area of research to fabricate complex constructs without a donor site. Sodium dodecyl sulfate (SDS)-based protocols remain the predominant choice for decellularization despite the deleterious effects on tissue ultrastructure and capillary networks. We aimed to develop an automated decellularization process and compare different SDS perfusion times to optimize the protocol. METHODS: A three-dimensional-printed closed-system bioreactor capable of continuously perfusing fluid through the vasculature was used for decellularization. The artery and vein of rat epigastric fasciocutaneous free flaps were cannulated and connected to the bioreactor. Protocols had varying durations of 1% SDS solution (3, 5, and 10 days) followed by 1 day of 1% Triton X-100 and 1 day of 1x phosphate-buffered saline. The residual DNA was quantified. Microarchitecture of the constructs was assessed with histology, and the vascular network was visualized for qualitative assessment. RESULTS: The structural integrity and the microarchitecture of the extracellular matrix was preserved in the 3- and 5-day SDS perfusion groups; however, the subcutaneous tissue of the 10-day protocol lost its structure. Collagen and elastin structures of the pedicle vessels were not compromised by the decellularization process. Five-day SDS exposure group had the least residual DNA content (p < 0.001). Across all protocols, skin consistently had twice as much residual DNA over the subcutaneous tissues. CONCLUSION: A compact and integrated bioreactor can automate decellularization of free flaps to bioengineer regenerative constructs for future use in reconstruction of complex defects. A decellularization protocol with 5 days of 1% SDS exposure was the most successful to keep the residual DNA content at a minimum while preserving the structural integrity of the tissues.
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Retalhos de Tecido Biológico , Ratos , Animais , Dodecilsulfato de Sódio/farmacologia , Dodecilsulfato de Sódio/análise , Dodecilsulfato de Sódio/química , Roedores , Matriz Extracelular/química , Matriz Extracelular/ultraestrutura , DNA/análise , DNA/farmacologia , Engenharia Tecidual/métodos , Alicerces TeciduaisRESUMO
OBJECTIVE: This study aimed to prospectively assess outcomes for surgical autologous fat transfer (AFT) applied for traumatic and postsurgical craniofacial deformities. The minimally invasive nature of AFT has potential for reduced risk and superior outcomes compared with current reconstructive options. BACKGROUND: Craniofacial deformities have functional and psychosocial sequelae and can profoundly affect quality of life. Traditional reconstructive options are invasive, invasive, complex, and often lack precision in outcomes. Although AFT is safe, effective, and minimally invasive, only anecdotal evidence exists for reconstruction of craniofacial deformities. METHODS: In this Institutional Review Board-approved prospective cohort study, 20 subjects underwent AFT (average volume: 23.9â±â13.2âmL). Volume retention over time was determined using high-resolution computed tomography. Flow cytometry was used to assess cellular subpopulations and viability in the stromal vascular fraction. Quality of life assessments were performed. After the completion of 9-month follow-up, 5 subjects were enrolled for a second treatment. RESULTS: No serious adverse events occurred. Volume retention averaged 63â±â17% at 9 months. Three-month retention strongly predicted 9-month retention (r=0.996, P < 0.0001). There was no correlation between the total volume injected and retention. Patients undergoing a second procedure had similar volume retention as the first (P = 0.05). Age, sex, body mass index, and stromal vascular fraction cellular composition did not impact retention. Surprisingly, former smokers had greater volume retention at 9 months compared with nonsmokers (74.4% vs 56.2%, P = 0.009). Satisfaction with physical appearance (P = 0.002), social relationships (P = 0.02), and social functioning quality of life (P = 0.05) improved from baseline to 9 months. CONCLUSIONS: For craniofacial defects, AFT is less invasive and safer than traditional reconstructive options. It is effective, predictable, and reaches volume stability at 3 months. Patient-reported outcomes demonstrate a positive life-changing impact.
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Tecido Adiposo/transplante , Anormalidades Craniofaciais/cirurgia , Medidas de Resultados Relatados pelo Paciente , Procedimentos de Cirurgia Plástica/métodos , Qualidade de Vida , Adulto , Anormalidades Craniofaciais/diagnóstico , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tomografia Computadorizada por Raios X , Transplante Autólogo , Adulto JovemRESUMO
The trabecular meshwork (TM) is an ocular tissue that maintains intraocular pressure (IOP) within a physiologic range. Glaucoma patients have reduced TM cellularity and, frequently, elevated IOP. To establish a stem cell-based approach to restoring TM function and normalizing IOP, human adipose-derived stem cells (ADSCs) were induced to differentiate to TM cells in vitro. These ADSC-TM cells displayed a TM cell-like genotypic profile, became phagocytic, and responded to dexamethasone stimulation, characteristic of TM cells. After transplantation into naive mouse eyes, ADSCs and ADSC-TM cells integrated into the TM tissue, expressed TM cell markers, and maintained normal IOP, outflow facility, and extracellular matrix. Cell migration and affinity results indicated that the chemokine pair CXCR4/SDF1 may play an important role in ADSC-TM cell homing. Our study demonstrates the possibility of applying autologous or allogeneic ADSCs and ADSC-TM cells as a potential treatment to restore TM structure and function in glaucoma.
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Células-Tronco Adultas/citologia , Células-Tronco Adultas/transplante , Glaucoma/terapia , Malha Trabecular/citologia , Tecido Adiposo/citologia , Células-Tronco Adultas/efeitos dos fármacos , Animais , Câmara Anterior/citologia , Câmara Anterior/imunologia , Apoptose , Humor Aquoso/fisiologia , Diferenciação Celular , Movimento Celular , Células Cultivadas , Quimiotaxia , Dexametasona/farmacologia , Modelos Animais de Doenças , Glaucoma/patologia , Glaucoma/fisiopatologia , Xenoenxertos , Humanos , Técnicas In Vitro , Pressão Intraocular/fisiologia , Camundongos , Fagocitose , Medicina Regenerativa , Malha Trabecular/fisiologiaRESUMO
INTRODUCTION: Injuries to peripheral nerves cause distal muscle atrophy. The effects of adipose-derived stem cell (ASC) injections into a muscle after injury were examined. METHODS: A 1.5 cm defect in the rat sciatic nerve was created, resulting in gastrocnemius muscle atrophy. The nerve defect was repaired with autograft; DiR-labeled ASCs were injected into the gastrocnemius immediately postoperatively. Quantitation of gross musculature and muscle fiber area, cell survival, fibrosis, lipid deposition, inflammation, and reconstructive responses were investigated. RESULTS: ASCs were identified in the muscle at 6 weeks, where injections showed increased muscle mass percentage retained, larger average fiber area, and less overall lipid content accumulated throughout the musculature. Muscles having received ASCs showed increased presence of interlukin-10 and Ki67, and decreased inducible nitric oxide synthase (iNOS). DISCUSSION: This investigation is suggestive that an ASC injection into denervated muscle post-operatively is able to delay the onset of atrophy. Muscle Nerve 59:603-603, 2019.
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Músculo Esquelético/patologia , Atrofia Muscular/patologia , Traumatismos dos Nervos Periféricos/patologia , Nervo Isquiático/lesões , Transplante de Células-Tronco , Células-Tronco , Animais , Distrofina/metabolismo , Imuno-Histoquímica , Interleucina-10/metabolismo , Antígeno Ki-67/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , RatosRESUMO
Fat grafting was first described in the early 20th century but for many years remained a relatively underused technique due to the unreliability of long-term volume expansion. Significant improvements in reliability have been made in the last 2 decades and there is a large body of literature pertaining to extraction, processing and injection methods to obtain more lasting effects. However, volume loss and graft resorption remain a major challenge in the long term and lead to unpredictability in results. Enriching adipose graft with stromal vascular fraction, ex vivo cultured adipose stem cells and platelet-derived growth factor among others is one method under active investigation which may assist graft survival through a range of mechanisms including increased angiogenesis. Breaking adipose graft into smaller fragments such that engrafted cells have greater access to donor-site oxygenation and nutrition is another method which in theory may promote survival. Presently, adipose grafting in the face is usually for the addition of volume to fill defects. However, the stem-cell containing fraction of adipose grafting (stromal vascular fraction) appears to exert a rejuvenating effect on overlying skin and soft tissue when administered alone. The application of these low-volume injections represents a significant shift in thinking away from mere volume expansion. These techniques have been tested in a range of animal models and some human studies. In this review, the authors provide a broad overview of present research and highlight both limitations in previous research and current areas of investigation.
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Tecido Adiposo , Face , Rejuvenescimento , Tecido Adiposo/citologia , Tecido Adiposo/transplante , Animais , Face/fisiologia , Face/cirurgia , Humanos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologiaRESUMO
INTRODUCTION: Peripheral nerve damage is associated with high long-term morbidity. Because of beneficial secretome, immunomodulatory effects, and ease of clinical translation, transplantation with adipose-derived stem cells (ASC) represents a promising therapeutic modality. METHODS: Effect of ASC delivery in poloxamer hydrogel was assessed in a rat sciatic nerve model of critical-sized (1.5 cm) peripheral nerve injury. Nerve/muscle unit regeneration was assessed via immunostaining explanted nerve, quantitative polymerase chain reaction (qPCR), and histological analysis of reinnervating gastrocnemius muscle. RESULTS: On the basis of viability data, 10% poloxamer hydrogel was selected for in vivo study. Six weeks after transection and repair, the group treated with poloxamer delivered ASCs demonstrated longest axonal regrowth. The qPCR results indicated that the inclusion of ASCs appeared to result in expression of factors that aid in reinnervating muscle tissue. DISCUSSION: Delivery of ASCs in poloxamer addresses multiple facets of the complexity of nerve/muscle unit regeneration, representing a promising avenue for further study. Muscle Nerve 58: 251-260, 2018.
Assuntos
Adipócitos/transplante , Hidrogéis , Regeneração Nervosa/fisiologia , Nervos Periféricos/crescimento & desenvolvimento , Poloxâmero , Transplante de Células-Tronco/métodos , Adulto , Animais , Axônios/ultraestrutura , Feminino , Humanos , Imuno-Histoquímica , Neurônios Motores , Fibras Musculares Esqueléticas , Músculo Esquelético/crescimento & desenvolvimento , Músculo Esquelético/inervação , Ratos , Nervo Isquiático/lesões , Neuropatia Ciática/terapiaRESUMO
Background: The progressive decline in tissue mechanical strength that occurs with aging is hypothesized to be due to a loss of resident stem cell number and function. As such, there is concern regarding use of autologous adult stem cell therapy in older patients. To abrogate this, many patients elect to cryopreserve the adipose stromal-vascular fraction (SVF) of lipoaspirate, which contains resident adipose stem cells (ASC). However, it is not clear yet if there is any clinical benefit from banking cells at a younger age. Objectives: We performed a comparative analysis of SVF composition and ASC function from cells obtained under GMP conditions from the same three patients with time gap of 7 to 12 years. Methods: SVF, cryobanked under good manufacturing practice (GMP) conditions, was thawed and cell yield, viability, and cellular composition were assessed. In parallel, ASC proliferation and efficiency of tri-lineage differentiation were evaluated. Results: The results showed no significant differences existed in cell yield and SVF subpopulation composition within the same patient between harvest procedures 7 to 12 years apart. Further, no change in proliferation rates of cultured ASCs was found, and expanded cells from all patients were capable of tri-lineage differentiation. Conclusions: By harvesting fat from the same patient at two time points, we have shown that despite the natural human aging process, the prevalence and functional activity of ASCs in an adult mesenchymal stem cell, is highly preserved. Level of Evidence: 5.
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Tecido Adiposo/citologia , Células-Tronco Adultas/fisiologia , Envelhecimento/fisiologia , Senescência Celular/fisiologia , Células-Tronco Mesenquimais/fisiologia , Transplante de Células-Tronco/métodos , Células Estromais/fisiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Criopreservação , Feminino , Citometria de Fluxo , Humanos , Lipectomia , Masculino , Bancos de Tecidos/normas , Adulto JovemRESUMO
Chondroitin sulfate proteoglycans (CSPGs) are potent inhibitors of neural regeneration in the peripheral nervous system. Following nerve injury, inhibitory CSPGs accumulate within the endoneurium and Schwann cell basal lamina of the distal nerve stump. The utilization of chondroitinase ABC (chABC) has led to a marked increase in the ability of injured axons to regenerate across gaps through the CSPG-laden extracellular matrix. Experimental models have repeatedly shown chABC to be capable of degrading the CSPGs that hinder neurite outgrowth. In this article, the characterization of CSPGs, their upregulation following peripheral nerve injury, and potential mechanisms behind their growth and inhibition are described. To date, the literature supports that the adjunct use of chABC may be beneficial to peripheral nerve repair in digesting inhibitory CSPGs. chABC has also shown some indication of synergism with other therapies, such as stem cell transplantation. Evidence supporting the use of chondroitinase as a treatment modality in nerve repair, either alone or in combination with other agents, is reviewed within. Finally, several shortcomings of chABC are addressed, notably its thermal stability and physiologic longevity - both hindering its widespread clinical adoption. Future studies are warranted in order to optimize the therapeutic benefits of the chondroitinase enzyme.
Assuntos
Adjuvantes Imunológicos/farmacologia , Condroitina ABC Liase/farmacologia , Regeneração Nervosa/efeitos dos fármacos , Traumatismos dos Nervos Periféricos/terapia , Animais , Proteoglicanas de Sulfatos de Condroitina/metabolismo , Humanos , Imunomodulação , Traumatismos dos Nervos Periféricos/fisiopatologiaRESUMO
Since their isolation and characterization nearly a decade ago, adipose-derived stem cells (ASCs) have become one of the most popular adult stem cell populations for soft tissue engineering and regenerative medicine applications. Compared with other stem cell sources, ASCs offer several advantages including abundant autologous source, minor invasive harvesting (liposuction), significant proliferative capacity in culture, and multilineage potential. In this mini review, we focus on some of the more salient published clinical and preclinical data to date regarding ASC treatment for breast and facial soft tissue reconstruction.
Assuntos
Adipócitos/transplante , Mama , Face , Procedimentos de Cirurgia Plástica , Transplante de Células-Tronco , Transplante Autólogo/métodos , Cicatrização , Tecido Adiposo/citologia , Mama/patologia , Face/patologia , Feminino , Sobrevivência de Enxerto , Humanos , Lipectomia , Procedimentos de Cirurgia Plástica/métodos , Medicina Regenerativa , Transplante de Células-Tronco/métodos , Engenharia Tecidual/métodosRESUMO
Autologous fat transplantation has revolutionized soft tissue reconstruction, but conventional methods remain unpredictable as graft resorption rates are high due to lack of vascularization. The advent of adipose-derived stem cells (ASCs) has led to improvement of fat grafting outcomes, in part to their ability to undergo facile differentiation into adipose tissue, their angiogenic properties, and their ability to express and secrete multiple growth factors. This chapter discusses the isolation and characterization of human ASCs, its expansion in vitro, and relevant in vivo models for adipose tissue engineering.
Assuntos
Tecido Adiposo , Transplante de Células-Tronco Mesenquimais , Humanos , Adipócitos , Diferenciação Celular , Neovascularização Fisiológica , Engenharia TecidualRESUMO
Background: Microsurgical techniques have revolutionized the field of reconstructive surgery and are the mainstay for complex soft tissue reconstruction. However, their limitations have promoted the development of viable alternatives. This article seeks to explore technologies that have the potential of revolutionizing microsurgical reconstruction as it is currently known, reflect on current and future vascularized composite allotransplantation (VCA) practices, as well as describe the basic science within emerging technologies and their potential translational applications. Methods: A literature review was performed of the technologies that may represent the future of microsurgery: vascularized tissue engineering (VCA) and flap-specific tissue engineering. Results: VCA has shown great promise and has already been employed in the clinical setting (especially in face and limb transplantation). Immunosuppression, logistics, cost, and regulatory pathways remain barriers to overcome to make it freely available. Vascularized and flap-specific tissue engineering remain a laboratory reality but have the potential to supersede VCA. The capability of creating an off-the-shelf free flap matching the required tissue, size, and shape is a significant advantage. However, these technologies are still at the early stage and require significant advancement before they can be translated into the clinical setting. Conclusion: VCA, vascularized tissue engineering, and flap-specific bioengineering represent possible avenues for the evolution of current microsurgical techniques. The next decade will elucidate which of these three strategies will evolve into a tangible translational option and hopefully bring a paradigm shift of reconstructive surgery.
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BACKGROUND: Mechanical emulsification of adipose tissue to concentrate protein and stromal cell components (ie, nanofat) has gained considerable interest in clinical practice. Although the regenerative potential of nanofat has largely been used in aesthetic applications, these effects have considerable potential in reconstruction as well. Here, the authors investigated the therapeutic properties of nanofat injected directly into the denervated gastrocnemius after a sciatic nerve injury in Lewis rats. METHODS: Muscle denervation was induced by transecting and immediately repairing the sciatic nerve. Inguinal and subcutaneous adipose was harvested from donor rodents, processed into nanofat, and then injected intramuscularly into the gastrocnemius. Gait analysis was performed weekly. Rodents were euthanized at 9 and 12 weeks, after which tetanic contraction force was measured, and gene expression, histology, and cytokine multiplexing were performed. RESULTS: Intramuscular injection of nanofat significantly increased maximum tetanic force generation at 9 and 12 weeks. The forces of the nanofat-injected gastrocnemii were better correlated to their contralateral gastrocnemii relative to controls. Muscle repair-associated inflammatory gene expressions were significantly up-regulated in nanofat-injected gastrocnemii. Cytokines interleukin (IL)-1ß, IL-18, vascular endothelial growth factor, granulocyte-macrophage colony-stimulating factor, and tissue inhibitor of metalloproteinase-1 were significantly higher in nanofat-injected gastrocnemii relative to control gastrocnemii, and the tetanic force was linearly and significantly correlated to IL-1ß and IL-18 and their interacting effects. CONCLUSIONS: Intramuscular injection of emulsified adipose tissue (nanofat) significantly increased gastrocnemii contraction force after sciatic nerve injury, with prolonged reconstructive inflammation by means of CD68, inducible nitric oxide synthase, IL-1ß, and IL-18 all being potential mechanisms for this recovery. This application could potentially increase the therapeutic breadth of nanofat to include muscular recovery after nerve injury. CLINICAL RELEVANCE STATEMENT: The authors' study investigates a clinically translatable therapy to mitigate muscle atrophy after nerve injury.
Assuntos
Traumatismos dos Nervos Periféricos , Neuropatia Ciática , Ratos , Animais , Injeções Intramusculares , Interleucina-18 , Inibidor Tecidual de Metaloproteinase-1 , Fator A de Crescimento do Endotélio Vascular , Ratos Endogâmicos Lew , Nervo Isquiático/lesões , Citocinas , Regeneração Nervosa/fisiologiaRESUMO
Background: Bioengineered nerve guides with glial cell line-derived neurotrophic factor (GDNF) support recovery after facial nerve injury by acting as regenerative scaffolds. Objective: To compare functional, electrophysiological, and histological outcomes after repair of rat facial nerve transection in control, empty nerve guide, and nerve guide with GDNF conditions. Methods: Rats underwent transection and primary repair of the buccal branch of the facial nerve and were divided into (1) transection and repair only, (2) transection and repair augmented with empty guide, (3) transection and repair augmented with GDNF-guide groups. Weekly measurements of the whisking movements were recorded. At 12 weeks, compound muscle action potentials (CMAPs) at the whisker pad were assessed, and samples were collected for histomorphometric analysis. Results: Rats in GDNF-guide group displayed the earliest peak in normalized whisking amplitude. CMAPs were significantly higher after GDNF-guide placement. Mean fiber surface area of the target muscle, axonal count of the injured branch, and the number of Schwann cells were highest with GDNF guides. Conclusion: The biodegradable nerve guide containing double-walled GDNF microspheres enhanced recovery after facial nerve transection and primary repair.
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Traumatismos do Nervo Facial , Ratos , Animais , Humanos , Traumatismos do Nervo Facial/cirurgia , Fator Neurotrófico Derivado de Linhagem de Célula Glial/uso terapêutico , Nervo Facial/cirurgia , MicroesferasRESUMO
The recent identification of a mesenchymal stem cell population in adipose tissue has led to an abundance of research focused on the regenerative properties of these cells. As such, adipose-derived stem cells (ASCs) and potential therapies in craniofacial regeneration have been widely studied. This review will discuss the identification and potential of ASCs, and specifically, preclinical and clinical studies using ASCs in craniofacial repair. Studies involving ASCs in the repair of defects caused by craniosynostosis and Treacher Collins syndrome will be discussed. A comprehensive review of the literature will be presented, focusing on fat grafting and biomaterials-based approaches that include ASCs for craniofacial regeneration.
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Adipócitos/citologia , Tecido Adiposo/citologia , Células-Tronco Adultas/citologia , Anormalidades Craniofaciais/terapia , Células-Tronco/citologia , Engenharia Tecidual/métodos , Adipócitos/transplante , Células-Tronco Adultas/transplante , Regeneração Tecidual Guiada , Humanos , Regeneração , Medicina Regenerativa/métodosRESUMO
Vascularization is crucial for implantation of engineered tissues in reconstructive surgery. Polypeptides encapsulated in microspheres can be efficiently transported to their site of action and released in a sustained dosage. We evaluated the effect of delivering vascular endothelial growth factor (VEGF)-encapsulated microspheres in a lipoaspirate scaffold on vascularization and tissue survival. The VEGF-loaded (n=6) and empty (n=6) poly(lactic-co-glycolic acid) microspheres in human lipoaspirate and the human lipoaspirate alone (n=6) were injected subcutaneously into the flanks of athymic nude mice. Three mice from each group were killed, and grafts were explanted at weeks 3 and 6. Increases in mass and volume of VEGF samples, as well as decreases in empty and lipoaspirate-only samples, were observed at 3 and 6 weeks, reaching statistical significance at 6 weeks. Hematoxylin and eosin and CD31+ imaging demonstrated significantly greater vascularization in VEGF samples than in both the empty and lipoaspirate-only groups at both 3 and 6 weeks.
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Tecido Adiposo Branco/transplante , Indutores da Angiogênese/farmacologia , Regeneração Tecidual Guiada/métodos , Microesferas , Neovascularização Fisiológica/efeitos dos fármacos , Alicerces Teciduais , Fator A de Crescimento do Endotélio Vascular/farmacologia , Tecido Adiposo Branco/irrigação sanguínea , Tecido Adiposo Branco/crescimento & desenvolvimento , Indutores da Angiogênese/administração & dosagem , Animais , Feminino , Sobrevivência de Enxerto , Humanos , Lipectomia , Camundongos , Camundongos Nus , Fator A de Crescimento do Endotélio Vascular/administração & dosagemRESUMO
Injury to the facial nerve can occur after different etiologies and range from simple transection of the branches to varying degrees of segmental loss. Management depends on the extent of injury and options include primary repair for simple transections and using autografts, allografts, or conduits for larger gaps. Tissue engineering plays an important role to create artificial materials that are able to mimic the nerve itself without extra morbidity in the patients. The use of neurotrophic factors or stem cells inside the conduits or around the repair site is being increasingly studied to enhance neural recovery to a greater extent. Preclinical studies remain the hallmark for development of these novel approaches and translation into clinical practice. This review will focus on preclinical models of repair after facial nerve injury to help researchers establish an appropriate model to quantify recovery and analyze functional outcomes. Different bioengineered materials, including conduits and nerve grafts, will be discussed based on the experimental animals that were used and the defects introduced. Future directions to extend the applications of processed nerve allografts, bioengineered conduits, and cues inside the conduits to induce neural recovery after facial nerve injury will be highlighted. Impact statement Recovery after facial nerve injury is a complex process, which involves different management options such as primary repair or the use of nerve grafts or conduits. Various tissue-engineered approaches are increasingly studied on preclinical models with limited, but promising, translation to the clinical setting. Herein, preclinical models focusing on different recovery methods after facial nerve injury are comprehensively reviewed based on the experimental animals used. The review provides key insights into current developments and future directions on this highly relevant topic to help researchers further expand the field of tissue engineering and facial nerve recovery.
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Traumatismos do Nervo Facial , Procedimentos de Cirurgia Plástica , Animais , Nervo Facial/fisiologia , Traumatismos do Nervo Facial/terapia , Humanos , Regeneração Nervosa/fisiologia , Procedimentos de Cirurgia Plástica/métodos , Engenharia TecidualRESUMO
A robust synthetic strategy where polysaccharide derivative precursors react through aqueous Diels-Alder chemistry without the involvement of catalysts and coupling reagents, allowing for the direct encapsulation of positive and negative proteins within biodegradable hydrogels. The results demonstrated that the aqueous Diels-Alder chemistry provides an extremely selective reaction and proceeds with high efficiency for polysaccharide bioconjugation. This synthetic approach uniquely allows for the direct fabrication of biologically functionalized gels with ideal structures, which provides a competitive alternative to conventional conjugation techniques such as click chemistry.
Assuntos
Materiais Biocompatíveis/síntese química , Química Orgânica/métodos , Hidrogéis/síntese química , Polissacarídeos/química , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Materiais Biocompatíveis/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Humanos , Hidrogéis/química , Insulina/farmacologia , Maleimidas/química , PolimerizaçãoRESUMO
Nonhealing wounds remain a significant challenge for plastic surgeons. More than 600,000 people suffer from venous ulcers and 1.5 to 3 million people are being treated for pressure sores every year in the United States. The use of tissue engineering techniques such as stem-cell therapy and gene therapy to improve wound healing is a promising strategy. Adipose tissue represents a source of cells that may be able to enhance wound healing. Adipose-derived stem cells (ASCs) are adult stem cells that are easily harvested and of great interest for plastic surgeons. Specifically, ASCs secrete angiogenic growth factors that can induce tissue regeneration. This review describes innovative research strategies using ASCs therapies for treatment of chronic, nonhealing wounds.
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Tecido Adiposo/citologia , Transplante de Células-Tronco , Células-Tronco , Cicatrização , Ferimentos e Lesões/cirurgia , Animais , Doença Crônica , Humanos , Células-Tronco/fisiologia , Cicatrização/fisiologiaRESUMO
Silk fibroin conduits were designed with appropriate porosity for peripheral nerve repair. The aim of this work was to use these conduits to examine cell inflammatory responses and functional recovery in a sciatic nerve defect model. A total of 45 randomized Lewis rats were used to create an 8-mm defect bridged by a silk guide, commercial collagen guide, or an autograft. After 1, 4, and 8 weeks, macrophage recruitment, percentage of newly formed collagen, number of myelinated axons, and gastrocnemius muscle mass were evaluated. Following 8 weeks, ED1+ cells in autograft and silk conduits decreased to <1% and 17% of week 1 values, respectively. Collagen formation revealed no difference for all measured time points, suggesting a similar foreign body response. Myelinated axon counts within the silk guide revealed a greater number of proximal spouts and distal connections than collagen guides. Gastrocnemius weights demonstrated a 27% decrease between silk and autografts after 8 weeks. This study demonstrates that, in addition to tailorable degradation rates, our silk conduits possess a favorable immunogenicity and remyelination capacity for nerve repair.