Browsing by Subject "Wound healing"
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Item Open Access 3D-MSCs A151 ODN-loaded exosomes are immunomodulatory and reveal a proteomic cargo that sustains wound resolution(Elsevier B.V., 2022-11) Camões, Sérgio P.; Bulut, Özlem; Yazar, Volkan; Gaspar, Maria M.; Simões, Sandra; Ferreira, Rita; Vitorino, Rui; Santos, Jorge M.; Gürsel, İhsan; Miranda, Joana P.Introduction: Non-healing wounds remain a major burden due to the lack of effective treatments. Mesenchymal stem cell-derived exosomes (MSC-Exo) have emerged as therapeutic options given their pro-regenerative and immunomodulatory features. Still, little is known on the exact mechanisms mediated by MSC-Exo. Importantly, modulation of their efficacy through 3D-physiologic cultures together with loading strategies continues underexplored. Objectives: To uncover the MSC-Exo-mediated mechanism via proteomic analyses, and to use 3D-culture and loading technologies to expand MSC-Exo efficacy for cutaneous wound healing. Methods: MSC-Exo were produced in either 3D or 2D cultures (Exo3D/Exo2D) and loaded with an exogenous immunosuppressive oligodeoxynucleotide (A151 ODN). Both, loaded and naïve exosomes were characterised regarding size, morphology and the presence of specific protein markers; while IPA analyses enabled to correlate their protein content with the effects observed in vitro and in vivo. The Exo3D/Exo2D regenerative potential was evaluated in vitro by assessing keratinocyte and fibroblast mitogenicity, motogenicity, and cytokine secretion as well as using an in vivo wound splinting model. Accordingly, the modulation of inflammatory and immune responses by A151-loaded Exo3D/Exo2D was also assessed. Results: Exo3D stimulated mitogenically and motogenically keratinocytes and fibroblasts in vitro, with upregulation of IL-1α and VEGF-α or increased secretion of TGF-β, TNF-α and IL-10. In vivo, Exo3D reduced the granulation tissue area and promoted complete re-epithelization of the wound. These observations were sustained by the proteomic profiling of the Exo3D cargo that identified wound healing-related proteins, such as TGF-β, ITGA1-3/5, IL-6, CDC151, S100A10 and Wnt5α. Moreover, when loaded with A151 ODN, Exo3D differentially mediated wound healing-related trophic factors reducing the systemic levels of IL-6 and TNF-α at the late stage of wound healing in vivo. Conclusion: Our results support the potential of A151-loaded Exo3D for the treatment of chronic wounds by promoting skin regeneration, while modulating the systemic levels of the pro-inflammatory cytokines. © 2022Item Open Access Angiogenic heparin-mimetic peptide nanofiber gel improves regenerative healing of acute wounds(American Chemical Society, 2017) Uzunalli, G.; Mammadov R.; Yesildal, F.; Alhan, D.; Ozturk, S.; Ozgurtas, T.; Güler, Mustafa O.; Tekinay, A. B.Wound repair in adult mammals typically ends with the formation of a scar, which prevents full restoration of the function of the healthy tissue, although most of the wounded skin heals. Rapid and functional recovery of major wound injuries requires therapeutic approaches that can enhance the healing process via overcoming mechanical and biochemical problems. In this study, we showed that self-assembled heparin-mimetic peptide nanofiber gel was an effective bioactive wound dressing for the rapid and functional repair of full-thickness excisional wounds in the rat model. The bioactive gel-treated wounds exhibited increased angiogenesis (p < 0.05), re-epithelization (p < 0.05), skin appendage formation, and granulation tissue organization (p < 0.05) compared to sucrose-treated samples. Increased blood vessel numbers in the gel-treated wounds on day 7 suggest that angiogenesis played a key role in improvement of tissue healing in bioactive gel-treated wounds. Overall, the angiogenic heparin-mimetic peptide nanofiber gel is a promising platform for enhancing the scar-free recovery of acute wounds.Item Open Access Angiogenic peptide nanofibers improve wound healing in STZ-induced diabetic rats(American Chemical Society, 2016-06) Senturk, B.; Mercan, S.; Delibasi, T.; Güler, Mustafa O.; Tekinay, A. B.Low expressions of angiogenic growth factors delay the healing of diabetic wounds by interfering with the process of blood vessel formation. Heparin mimetic peptide nanofibers can bind to and enhance production and activity of major angiogenic growth factors, including VEGF. In this study, we showed that heparin mimetic peptide nanofibers can serve as angiogenic scaffolds that allow slow release of growth factors and protect them from degradation, providing a new therapeutic way to accelerate healing of diabetic wounds. We treated wounds in STZ-induced diabetic rats with heparin mimetic peptide nanofibers and studied repair of full-thickness diabetic skin wounds. Wound recovery was quantified by analyses of re-epithelialization, granulation tissue formation and blood vessel density, as well as VEGF and inflammatory response measurements. Wound closure and granulation tissue formation were found to be significantly accelerated in heparin mimetic gel treated groups. In addition, blood vessel counts and the expressions of alpha smooth muscle actin and VEGF were significantly higher in bioactive gel treated animals. These results strongly suggest that angiogenic heparin mimetic nanofiber therapy can be used to support the impaired healing process in diabetic wounds.Item Open Access Bioactive peptide nanofibers for tissue regeneration(2016-01) Uzunallı, GözdeDefects in the tissues or organs caused by trauma or diseases can have detrimental effects on all aspects of patients’ life quality. During the last three decades, considerable developments have been made in tissue engineering and regenerative medicine in order to find alternative treatment methods to recover tissue function after injury. These methods are based on the development of materials that are uniquely suited to the specific requirements of the tissue type and the repair process itself. Consequently, the implanted biomaterial must be compatible with biological systems and capable of delivering the signals necessary to facilitate tissue repair. In the present thesis, peptide amphiphile molecules were used to meet these requirements and develop next-generation biomaterials that are able to enhance the repair process while minimally affecting the integrity of surrounding tissues. Peptide amphiphiles are molecules that naturally self-assemble into nanofibrous hydrogel structures that closely emulate the composition of the extracellular matrix. As peptide amphiphiles contain amino acid sequences, bioactive signals can also be integrated into their structure to create a biocompatible environment and enhance the survival and proliferation of the resident cell population. In the scope of the present thesis, peptide amphiphile systems were utilized in three distinct applications. The first chapter covers the fundamentals of regenerative medicine and tissue engineering, the interactions between biomaterials and cells and extracellular materials, and the materials that are commonly used for these applications. The second chapter details the use of fibronectin- and laminin-derived peptide amphiphiles for the regeneration of corneal injuries. The third chapter investigates the ability of heparin-mimetic peptide hydrogels to facilitate the survival of pancreatic islets in vitro and demonstrates that islets transplanted in tandem with peptide gels trigger a local angiogenic response, decrease blood glucose levels and retain these functionalities even after 28 days of observation. The fourth chapter concerns the application of heparin-mimetic peptide amphiphile molecules for the recovery of acute wound injuries through the establishment of a well-ordered collagen matrix and the enhancement of the re-epithelialization process. Distinct peptide amphiphiles bearing bioactive signals conductive to tissue development were developed and utilized in all three studies, and the use of these materials has been demonstrated to serve as an adequate means of enhancing tissue repair.Item Open Access Heparin mimetic peptide nanofiber gel promotes regeneration of full thickness burn injury(Elsevier Ltd, 2017) Yergoz, F.; Hastar, N.; Cimenci, C. E.; Ozkan, A. D.; Güler, Mustafa O.; Tekinay, A. B.; Tekinay, T.; Güler, Mustafa O.Burn injuries are one of the most common types of trauma worldwide, and their unique physiology requires the development of specialized therapeutic materials for their treatment. Here, we report the use of synthetic, functional and biodegradable peptide nanofiber gels for the improved healing of burn wounds to alleviate the progressive loss of tissue function at the post-burn wound site. These bioactive nanofiber gels form scaffolds that recapitulate the structure and function of the native extracellular matrix through signaling peptide epitopes, which can trigger angiogenesis through their affinity to basic growth factors. In this study, the angiogenesis-promoting properties of the bioactive scaffolds were utilized for the treatment of a thermal burn model. Following the excision of necrotic tissue, bioactive gels and control solutions were applied topically onto the wound area. The wound healing process was evaluated at 7, 14 and 21 days following injury through histological observations, immunostaining and marker RNA/protein analysis. Bioactive peptide nanofiber-treated burn wounds formed well-organized and collagen-rich granulation tissue layers, produced a greater density of newly formed blood vessels, and exhibited increased re-epithelialization and skin appendage development with minimal crust formation, while non-bioactive peptide nanofibers and the commercial wound dressing 3M™ Tegaderm™ did not exhibit significant efficiency over sucrose controls. Overall, the heparin-mimetic peptide nanofiber gels increased the rate of repair of burn injuries and can be used as an effective means of facilitating wound healing.Item Open Access Wound healing applications of nanomaterials(John Wiley & Sons, 2016-03-11) Şentürk, Berna; Uzunalli, Gözde; Mammadov, Rashad; Güler, Mustafa O.; Tekinay, Ayşe B.; Güler, Mustafa O.; Tekinay, Ayşe B.This chapter first provides an overview of skin structure and its biological response to the tissue loss in wound healing process and reviews the classical and next‐generation scaffolds and materials that are used to minimize scar formation while accelerating the healing process. The chapter also provides a snapshot of the natural and synthetic biomaterials currently in clinical use in this field. Wound healing occurs in nearly all tissue types, and the order of events during the healing process is similar across different tissues. Natural materials are required to exhibit certain characteristics to be considered suitable for use as wound dressings. A large number of natural materials, such as collagen, gelatin, laminin, and chitin/chitosan, have been used as electrospun scaffolds for tissue engineering. Salient features of these materials are designed in an attempt to provide a desired niche for robust wound healing process.