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Mozafari M. - One of the best experts on this subject based on the ideXlab platform.

  • 3D Protein-Based Bilayer Artificial Skin for the Guided Scarless Healing of Third-Degree Burn Wounds in Vivo
    2018
    Co-Authors: Gholipourmalekabadi M., Seifalian A.m., Urbanska A.m., Hardy J.g., Madjd Z., Hashemi S.m., Ghanbarian H., Brouki Milan P., Mozafari M.
    Abstract:

    Severe burn injuries can lead to delays in healing and devastating scar formation. Attempts have been made to develop a suitable skin substitute for the scarless healing of such skin wounds. Currently, there is no effective strategy for completely scarless healing after the thermal injuries. In our recent work, we fabricated and evaluated a 3D protein-based artificial skin made from decellularized human amniotic membrane (AM) and electrospun nanofibrous silk fibroin (ESF) in vitro. We also characterized both biophysical and cell culture investigation to establish in vitro performance of the developed bilayer scaffolds. In this report, we evaluate the appropriate utility of this fabricated bilayered artificial skin in vivo with particular emphasis on healing and scar formation due to the biochemical and biomechanical complexity of the skin. For this work, AM and AM/ESF membranes alone or seeded with adipose-tissue-derived mesenchymal stem cells (AT-MSCs) are implanted on full-thickness burn wounds in mice. The healing efficacy and scar formation are evaluated at 7, 14, and 28 days post-implantation in vivo. Our data reveal that ESF accelerates the wound-healing process through the early recruitment of inflammatory cells such as macrophages into the defective site as well as the up-regulation of angiogenic factors from the AT-MSCs and the facilitation of the Remodeling Phase. In vivo application of the prepared AM/ESF membrane seeded with the AT-MSCs reduces significantly the post-burn scars. The in vivo data suggest that the potential applications of the AM/ESF bilayered artificial skin may be considered a clinical translational product with stem cells to guide the scarless healing of severe burn injuries. Copyright © 2018 American Chemical Society

  • 3D protein-based bilayer artificial skin for guided scarless healing of full-thickness burn wounds in vivo
    'American Chemical Society (ACS)', 2018
    Co-Authors: Gholipourmalekabadi M., Madjd Z., Ghanbarian H., Brouki Milan P., Seifalian A., Urbanska A., Omrani M. D., Hardy J., Hashemi S. M., Mozafari M.
    Abstract:

    Severe burn injuries can lead to delays in healing and devastating scar formation. Attempts have been made to develop a suitable skin substitute for the scarless healing of such skin wounds. Currently, there is no effective strategy for completely scarless healing after the thermal injuries. In our recent work, we fabricated and evaluated a 3D protein-based artificial skin made from decellularized human amniotic membrane (AM) and electrospun nanofibrous silk fibroin (ESF) in vitro. We also characterized both biophysical and cell culture investigation to establish in vitro performance of the developed bilayer scaffolds. In this report, we evaluate the appropriate utility of this fabricated bilayered artificial skin in vivo with particular emphasis on healing and scar formation due to the biochemical and biomechanical complexity of the skin. For this work, AM and AM/ESF membranes alone or seeded with adipose-tissue-derived mesenchymal stem cells (AT-MSCs) are implanted on full-thickness burn wounds in mice. The healing efficacy and scar formation are evaluated at 7, 14, and 28 days post-implantation in vivo. Our data reveal that ESF accelerates the wound-healing process through the early recruitment of inflammatory cells such as macrophages into the defective site as well as the up-regulation of angiogenic factors from the AT-MSCs and the facilitation of the Remodeling Phase. In vivo application of the prepared AM/ESF membrane seeded with the AT-MSCs reduces significantly the post-burn scars. The in vivo data suggest that the potential applications of the AM/ESF bilayered artificial skin may be considered a clinical translational product with stem cells to guide the scarless healing of severe burn injuries.We express our appreciation to Prof. Bahram Kazemi and Dr. Nariman Mosaffa for their constructive comments on this manuscript. S.C.K. presently holds an ERA Chair Full Professor position at the 3Bs Research Group, University of Minho, Portugal, supported by the European Union Framework Programme for Research and Innovation Horizon 2020 under grant agreement no. 668983, FoReCaST.info:eu-repo/semantics/publishedVersio

Howard Levinson - One of the best experts on this subject based on the ideXlab platform.

  • biostable electrospun microfibrous scaffolds mitigate hypertrophic scar contraction in an immune competent murine model
    Acta Biomaterialia, 2016
    Co-Authors: Elizabeth R Lorden, Kyle J Miller, Latif Bashirov, Mohamed M Ibrahim, Ellen Hammett, Kam W Leong, Syandan Chakraborty, Carlos Quilestorres, Angelica M Selim, Howard Levinson
    Abstract:

    Abstract Burn injuries in the United States account for over one million hospital admissions per year, with treatment estimated at four billion dollars. Of severe burn patients, 30–90% will develop hypertrophic scars (HSc). In this study, we evaluate the impact of an elastomeric, randomly-oriented biostable polyurethane (PU) scaffold on HSc-related outcomes. In vitro, fibroblast-seeded PU scaffolds contracted significantly less and demonstrated fewer αSMA+ myofibroblasts compared to fibroblast-seeded collagen lattices. In a murine HSc model, collagen coated PU (ccPU) scaffolds significantly reduced HSc contraction as compared to untreated control wounds and wounds treated with the clinical standard of care. Our data suggest that electrospun ccPU scaffolds meet the requirements to reduce HSc contraction including reduction of in vitro HSc related outcomes, diminished scar stiffness, and reduced scar contraction. While clinical dogma suggests treating severe burn patients with rapidly biodegrading skin equivalents, our data suggest that a more long-term scaffold may possess merit in reducing HSc. Statement of Significance In severe burns treated with skin grafting, between 30% and 90% of patients develop hypertrophic scars (HSc). There are no therapies to prevent HSc, and treatments are marginally effective. This work is the first example we are aware of which studies the impact of a permanent electrospun elastomer on HSc contraction in a murine model that mimics the human condition. Collagen coated polyurethane scaffolds decrease αSMA+ myofibroblast formation in vitro, prevent stiffening of scar tissue, and mitigate HSc contraction. Unlike current standards of care, electrospun, polyurethane scaffolds do not lose architecture over time. We propose that the future bioengineering strategy of mitigating HSc contraction should consider a long-term elastomeric matrix which persists within the wound bed throughout the Remodeling Phase of repair.

  • Temporal spatial expression and function of non-muscle myosin II isoforms IIA and IIB in scar Remodeling
    Laboratory Investigation, 2011
    Co-Authors: Jennifer E Bond, Maria Angelica Selim, Trung Q Ho, Cedric L Hunter, Edith V Bowers, Howard Levinson
    Abstract:

    Scar contracture is believed to be caused by the cell contractility during the Remodeling Phase of wound healing. Cell contractility is mediated by non-muscle myosin II (NMMII) and actin, but the temporal-spatial expression profile of NMMII isoforms A and B (IIA and IIB) during the Remodeling Phase and the role of NMMII in scar fibroblast tissue Remodeling are unknown. Human scar tissue immunostained for IIA and IIB showed that both isoforms were highly expressed in scar tissue throughout the Remodeling Phase of repair and expression levels returned to normal after the Remodeling Phase. Human scar tissue immunostained for β -, γ - and α –smooth muscle actin showed that all isoforms were consistently expressed throughout the Remodeling Phase of repair. The β - and γ -smooth muscle actin were widely expressed throughout the dermis, but α -smooth muscle actin was only locally expressed within the dermis. In vitro , fibroblasts explanted from scar tissue were shown to express more IIA than fibroblasts explanted from normal tissue and scar fibroblasts contracted collagen lattices to a greater extent than normal fibroblasts. Blebbistatin was used to demonstrate the function of NMMII in collagen lattice contraction. In normal tissue, fibroblasts are stress-shielded from external tensile stress by the extracellular matrix. After dermal injury and during Remodeling, fibroblasts are exposed to a matrix of increased stiffness. The effect of matrix stiffness on IIA and IIB expression was examined. IIA expression was greater in fibroblasts cultured in collagen lattices with increasing stiffness, and in fibroblasts cultured on glass slides compared with polyacrylamide gels with stiffness of 1 kPa. In conclusion, NMMII and actin isoform expression changes coordinately with the Remodeling Phase of repair, and NMMII is increased as matrix stiffness increases. As NMMII expression increases, so does the fibroblast contractility.

Kam W Leong - One of the best experts on this subject based on the ideXlab platform.

  • biostable electrospun microfibrous scaffolds mitigate hypertrophic scar contraction in an immune competent murine model
    Acta Biomaterialia, 2016
    Co-Authors: Elizabeth R Lorden, Kyle J Miller, Latif Bashirov, Mohamed M Ibrahim, Ellen Hammett, Kam W Leong, Syandan Chakraborty, Carlos Quilestorres, Angelica M Selim, Howard Levinson
    Abstract:

    Abstract Burn injuries in the United States account for over one million hospital admissions per year, with treatment estimated at four billion dollars. Of severe burn patients, 30–90% will develop hypertrophic scars (HSc). In this study, we evaluate the impact of an elastomeric, randomly-oriented biostable polyurethane (PU) scaffold on HSc-related outcomes. In vitro, fibroblast-seeded PU scaffolds contracted significantly less and demonstrated fewer αSMA+ myofibroblasts compared to fibroblast-seeded collagen lattices. In a murine HSc model, collagen coated PU (ccPU) scaffolds significantly reduced HSc contraction as compared to untreated control wounds and wounds treated with the clinical standard of care. Our data suggest that electrospun ccPU scaffolds meet the requirements to reduce HSc contraction including reduction of in vitro HSc related outcomes, diminished scar stiffness, and reduced scar contraction. While clinical dogma suggests treating severe burn patients with rapidly biodegrading skin equivalents, our data suggest that a more long-term scaffold may possess merit in reducing HSc. Statement of Significance In severe burns treated with skin grafting, between 30% and 90% of patients develop hypertrophic scars (HSc). There are no therapies to prevent HSc, and treatments are marginally effective. This work is the first example we are aware of which studies the impact of a permanent electrospun elastomer on HSc contraction in a murine model that mimics the human condition. Collagen coated polyurethane scaffolds decrease αSMA+ myofibroblast formation in vitro, prevent stiffening of scar tissue, and mitigate HSc contraction. Unlike current standards of care, electrospun, polyurethane scaffolds do not lose architecture over time. We propose that the future bioengineering strategy of mitigating HSc contraction should consider a long-term elastomeric matrix which persists within the wound bed throughout the Remodeling Phase of repair.

  • mitigation of hypertrophic scar contraction via an elastomeric biodegradable scaffold
    Biomaterials, 2015
    Co-Authors: Elizabeth R Lorden, Kyle J Miller, Latif Bashirov, Mohamed M Ibrahim, Ellen Hammett, Youngmee Jung, Manuel A Medina, Ali Rastegarpour, Maria Angelica Selim, Kam W Leong
    Abstract:

    Abstract Hypertrophic scar (HSc) occurs in 40–70% of patients treated for third degree burn injuries. Current burn therapies rely upon the use of bioengineered skin equivalents (BSEs), which assist in wound healing but do not prevent HSc contraction. HSc contraction leads to formation of a fixed, inelastic skin deformity. We propose that BSEs should maintain their architecture in the wound bed throughout the Remodeling Phase of repair to prevent HSc contraction. In this work we study a degradable, elastomeric, randomly oriented, electrospun micro-fibrous scaffold fabricated from the copolymer poly( l -lactide-co-e-caprolactone) (PLCL). PLCL scaffolds displayed appropriate elastomeric and tensile characteristics for implantation beneath a human skin graft. In vitro analysis using human dermal fibroblasts demonstrated that PLCL scaffolds decreased myofibroblast formation as compared to an in vitro HSc contraction model. Using a validated immune-competent murine HSc contraction model, we found that HSc contraction was significantly greater in animals treated with standard of care, Integra, as compared to those treated with collagen coated-PLCL (ccPLCL) scaffolds. Finally, wounds treated with ccPLCL were significantly less stiff than control wounds at d30 in vivo. Together, these data suggest that scaffolds which persist throughout the Remodeling Phase of repair may represent a clinically translatable method to prevent HSc contraction.

Elizabeth R Lorden - One of the best experts on this subject based on the ideXlab platform.

  • biostable electrospun microfibrous scaffolds mitigate hypertrophic scar contraction in an immune competent murine model
    Acta Biomaterialia, 2016
    Co-Authors: Elizabeth R Lorden, Kyle J Miller, Latif Bashirov, Mohamed M Ibrahim, Ellen Hammett, Kam W Leong, Syandan Chakraborty, Carlos Quilestorres, Angelica M Selim, Howard Levinson
    Abstract:

    Abstract Burn injuries in the United States account for over one million hospital admissions per year, with treatment estimated at four billion dollars. Of severe burn patients, 30–90% will develop hypertrophic scars (HSc). In this study, we evaluate the impact of an elastomeric, randomly-oriented biostable polyurethane (PU) scaffold on HSc-related outcomes. In vitro, fibroblast-seeded PU scaffolds contracted significantly less and demonstrated fewer αSMA+ myofibroblasts compared to fibroblast-seeded collagen lattices. In a murine HSc model, collagen coated PU (ccPU) scaffolds significantly reduced HSc contraction as compared to untreated control wounds and wounds treated with the clinical standard of care. Our data suggest that electrospun ccPU scaffolds meet the requirements to reduce HSc contraction including reduction of in vitro HSc related outcomes, diminished scar stiffness, and reduced scar contraction. While clinical dogma suggests treating severe burn patients with rapidly biodegrading skin equivalents, our data suggest that a more long-term scaffold may possess merit in reducing HSc. Statement of Significance In severe burns treated with skin grafting, between 30% and 90% of patients develop hypertrophic scars (HSc). There are no therapies to prevent HSc, and treatments are marginally effective. This work is the first example we are aware of which studies the impact of a permanent electrospun elastomer on HSc contraction in a murine model that mimics the human condition. Collagen coated polyurethane scaffolds decrease αSMA+ myofibroblast formation in vitro, prevent stiffening of scar tissue, and mitigate HSc contraction. Unlike current standards of care, electrospun, polyurethane scaffolds do not lose architecture over time. We propose that the future bioengineering strategy of mitigating HSc contraction should consider a long-term elastomeric matrix which persists within the wound bed throughout the Remodeling Phase of repair.

  • mitigation of hypertrophic scar contraction via an elastomeric biodegradable scaffold
    Biomaterials, 2015
    Co-Authors: Elizabeth R Lorden, Kyle J Miller, Latif Bashirov, Mohamed M Ibrahim, Ellen Hammett, Youngmee Jung, Manuel A Medina, Ali Rastegarpour, Maria Angelica Selim, Kam W Leong
    Abstract:

    Abstract Hypertrophic scar (HSc) occurs in 40–70% of patients treated for third degree burn injuries. Current burn therapies rely upon the use of bioengineered skin equivalents (BSEs), which assist in wound healing but do not prevent HSc contraction. HSc contraction leads to formation of a fixed, inelastic skin deformity. We propose that BSEs should maintain their architecture in the wound bed throughout the Remodeling Phase of repair to prevent HSc contraction. In this work we study a degradable, elastomeric, randomly oriented, electrospun micro-fibrous scaffold fabricated from the copolymer poly( l -lactide-co-e-caprolactone) (PLCL). PLCL scaffolds displayed appropriate elastomeric and tensile characteristics for implantation beneath a human skin graft. In vitro analysis using human dermal fibroblasts demonstrated that PLCL scaffolds decreased myofibroblast formation as compared to an in vitro HSc contraction model. Using a validated immune-competent murine HSc contraction model, we found that HSc contraction was significantly greater in animals treated with standard of care, Integra, as compared to those treated with collagen coated-PLCL (ccPLCL) scaffolds. Finally, wounds treated with ccPLCL were significantly less stiff than control wounds at d30 in vivo. Together, these data suggest that scaffolds which persist throughout the Remodeling Phase of repair may represent a clinically translatable method to prevent HSc contraction.

Ali Moshiri - One of the best experts on this subject based on the ideXlab platform.

  • role of tissue engineered collagen based tridimensional implant on the healing response of the experimentally induced large achilles tendon defect model in rabbits a long term study with high clinical relevance
    Journal of Biomedical Science, 2013
    Co-Authors: Abdolhamid Meimandiparizi, Ahmad Oryan, Ali Moshiri
    Abstract:

    Tendon injury is one of the orthopedic conditions poses with a significant clinical challenge to both the surgeons and patients. The major limitations to manage these injuries are poor healing response and development of peritendinous adhesions in the injured area. This study investigated the effectiveness of a novel collagen implant on tendon healing in rabbits. Seventy five mature White New-Zealand rabbits were divided into treated (n = 55) and control (n = 20) groups. The left Achilles tendon was completely transected and 2 cm excised. The defects of the treated animals were filled with collagen implants and repaired with sutures, but in control rabbits the defects were sutured similarly but the gap was left untreated. Changes in the injured and normal contralateral tendons were assessed weekly by measuring the diameter, temperature and bioelectrical characteristics of the injured area. Clinical examination was done and scored. Among the treated animals, small pilot groups were euthanized at 5, 10, 15, 20, 30, 40 and 60 (n = 5 at each time interval) and the remainder (n = 20) and the control animals at 120 days post injury (DPI). The lesions of all animals were examined at macroscopic and microscopic levels and the dry matter content, water delivery and water uptake characteristics of the lesions and normal contralateral tendons of both groups were analyzed at 120 DPI. No sign of rejection was seen in the treated lesions. The collagen implant was invaded by the inflammatory cells at the inflammatory Phase, followed by fibroplasia Phase in which remnant of the collagen implant were still present while no inflammatory reaction could be seen in the lesions. However, the collagen implant was completely absorbed in the Remodeling Phase and the newly regenerated tendinous tissue filled the gap. Compared to the controls, the treated lesions showed improved tissue alignment and less peritendinous adhesion, muscle atrophy and fibrosis. They also showed significantly better clinical scoring, indices for water uptake and water absorption, and bioelectrical characteristics than the controls. This novel collagen implant was biodegradable, biocompatible and possibly could be considered as a substitute for auto and allografts in clinical practice in near future.

  • a long term study on the role of exogenous human recombinant basic fibroblast growth factor on the superficial digital flexor tendon healing in rabbits
    Journal of Musculoskeletal & Neuronal Interactions, 2011
    Co-Authors: Ahmad Oryan, Ali Moshiri
    Abstract:

    BACKGROUND: This study was designed to investigate the effects of basic fibroblast growth factor on the Remodeling Phase of the tenotomized superficial digital flexor tendon in rabbits. METHODS: Forty white New Zealand mature male rabbits were divided randomly into two equal groups of treated and control. After tenotomy and surgical repair, using modified Kessler technique and running pattern, the injured legs were casted for 14 days. Human recombinant basic fibroblast growth factor (bFGF) was injected subcutaneously over the lesion on days 3, 7 and 10 post injuries. The control animals received normal saline injection similarly. The weight of the animals, tendon diameter, radiographic and ultrasonographic evaluations was conducted at weekly intervals. The animals were euthanized 84 days post-injury and the tendons were evaluated at macroscopic, histopathologic and ultrastructural level and were also assessed for biomechanical and percentage dry weight parameters. RESULTS: Treatment significantly reduced the diameter and increased the echogenicity and dry weight content of the injured tendons. Treatment also significantly enhanced the maturation of the tenoblasts, fibrillogenesis, the collagen fibrils' diameter, fibrillar density, stiffness, and ultimate and yield strength. CONCLUSIONS: Subcutaneous administration of human recombinant bFGF is effective in restoring the morphological and biomechanical properties of the injured SDFT in rabbits.