scholarly journals Bioengineered Skin Substitutes: The Role of Extracellular Matrix and Vascularization in the Healing of Deep Wounds

2019 ◽  
Vol 8 (12) ◽  
pp. 2083 ◽  
Author(s):  
Francesco Urciuolo ◽  
Costantino Casale ◽  
Giorgia Imparato ◽  
Paolo A. Netti
Keyword(s):  
Extracellular Matrix ◽  
Hair Follicles ◽  
Sweat Glands ◽  
Skin Wounds ◽  
Skin Substitutes ◽  
Skin Tissue Engineering ◽  
Skin Cells ◽  
Bioengineered Skin ◽  
A Current

The formation of severe scars still represents the result of the closure process of extended and deep skin wounds. To address this issue, different bioengineered skin substitutes have been developed but a general consensus regarding their effectiveness has not been achieved yet. It will be shown that bioengineered skin substitutes, although representing a valid alternative to autografting, induce skin cells in repairing the wound rather than guiding a regeneration process. Repaired skin differs from regenerated skin, showing high contracture, loss of sensitivity, impaired pigmentation and absence of cutaneous adnexa (i.e., hair follicles and sweat glands). This leads to significant mobility and aesthetic concerns, making the development of more effective bioengineered skin models a current need. The objective of this review is to determine the limitations of either commercially available or investigational bioengineered skin substitutes and how advanced skin tissue engineering strategies can be improved in order to completely restore skin functions after severe wounds.

scholarly journals Tissue engineering of skin and regenerative medicine for wound care

2018 ◽  
Vol 6 ◽  
Author(s):  
Steven T. Boyce ◽  
Andrea L. Lalley
Keyword(s):  
Chronic Wounds ◽  
Wound Care ◽  
Total Body Surface Area ◽  
Hair Follicles ◽  
Sweat Glands ◽  
Skin Wounds ◽  
Skin Substitutes ◽  
Anatomy And Physiology ◽  
Skin Cells ◽  
Skin Cell

Abstract ᅟ Engineering of biologic skin substitutes has progressed over time from individual applications of skin cells, or biopolymer scaffolds, to combinations of cells and scaffolds for treatment, healing, and closure of acute and chronic skin wounds. Skin substitutes may be categorized into three groups: acellular scaffolds, temporary substitutes containing allogeneic skin cells, and permanent substitutes containing autologous skin cells. Combined use of acellular dermal substitutes with permanent skin substitutes containing autologous cells has been shown to provide definitive wound closure in burns involving greater than 90% of the total body surface area. These advances have contributed to reduced morbidity and mortality from both acute and chronic wounds but, to date, have failed to replace all of the structures and functions of the skin. Among the remaining deficiencies in cellular or biologic skin substitutes are hypopigmentation, absence of stable vascular and lymphatic networks, absence of hair follicles, sebaceous and sweat glands, and incomplete innervation. Correction of these deficiencies depends on regulation of biologic pathways of embryonic and fetal development to restore the full anatomy and physiology of uninjured skin. Elucidation and integration of developmental biology into future models of biologic skin substitutes promises to restore complete anatomy and physiology, and further reduce morbidity from skin wounds and scar. This article offers a review of recent advances in skin cell thrapies and discusses the future prospects in cutaneous regeneration.

scholarly journals Role of Bradykinin Type 2 Receptors in Human Sweat Secretion: Translational Evidence Does Not Support a Functional Relationship

2021 ◽  
Vol 34 (3) ◽  
pp. 162-166
Author(s):  
Thad E. Wilson ◽  
Seetharam Narra ◽  
Kristen Metzler-Wilson ◽  
Artur Schneider ◽  
Kelsey A. Bullens ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Sweat Rate ◽  
Sweat Glands ◽  
Potential Therapeutic Target ◽  
Sweat Secretion ◽  
Hoe 140 ◽  
A Current

Bradykinin increases skin blood flow via a cGMP mechanism but its role in sweating in vivo is unclear. There is a current need to translate cell culture and nonhuman paw pad studies into in vivo human preparations to test for therapeutic viability for disorders affecting sweat glands. Protocol 1: physiological sweating was induced in 10 healthy subjects via perfusing warm (46–48°C) water through a tube-lined suit while bradykinin type 2 receptor (B2R) antagonist (HOE-140; 40 μM) and only the vehicle (lactated Ringer’s) were perfused intradermally via microdialysis. Heat stress increased sweat rate (HOE-140 = +0.79 ± 0.12 and vehicle = +0.64 ± 0.10 mg/cm<sup>2</sup>/min), but no differences were noted with B2R antagonism. Protocol 2: pharmacological sweating was induced in 6 healthy subjects via intradermally perfusing pilocarpine (1.67 mg/mL) followed by the same B2R antagonist approach. Pilocarpine increased sweating (HOE-140 = +0.38 ± 0.16 and vehicle = +0.32 ± 0.12 mg/cm<sup>2</sup>/min); again no differences were observed with B2R antagonism. Last, 5 additional subjects were recruited for various control experiments which identified that a functional dose of HOE-140 was utilized and it was not sudorific during normothermic conditions. These data indicate B2R antagonists do not modulate physiologically or pharmacologically induced eccrine secretion volumes. Thus, B2R agonist/antagonist development as a potential therapeutic target for hypo- and hyperhidrosis appears unwarranted.

scholarly journals Role of bradykinin type 2 receptors in human sweat secretion: translational evidence does not support a functional relationship

2020 ◽  
Author(s):  
Thad E. Wilson ◽  
Seetharam Narra ◽  
Kristen Metzler-Wilson ◽  
Artur Schneider ◽  
Kelsey A. Bullens ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Sweat Rate ◽  
Sweat Glands ◽  
Potential Therapeutic Target ◽  
Sweat Secretion ◽  
Hoe 140 ◽  
A Current

AbstractBradykinin increases skin blood flow via a cGMP mechanism but its role in sweating in vivo is unclear. There is a current need to translate cell culture and non-human paw pad studies into in vivo human preparations to test for therapeutic viability for disorders affecting sweat glands. Protocol 1: physiological sweating was induced in 10 healthy subjects via perfusing warm (46-48°C) water through a tube-lined suit while bradykinin type 2 receptor (B2R) antagonist (HOE-140; 40 μM) and only the vehicle (lactated Ringer’s) were perfused intradermally via microdialysis. Heat stress increased sweat rate (HOE-140 = +0.79±0.12 and vehicle = +0.64±0.10 mg/cm2/min), but no differences were noted with B2R antagonism. Protocol 2: pharmacological sweating was induced in 6 healthy subjects via intradermally perfusing pilocarpine (1.67 mg/ml) followed by the same B2R antagonist approach. Pilocarpine increased sweating (HOE-140 = +0.38±0.16 and vehicle = +0.32±0.12 mg/cm2/min); again no differences were observed with B2R antagonism. Lastly, 5 additional subjects were recruited for various control experiments which identified that a functional dose of HOE-140 was utilized and it was not sudorific during normothermic conditions. These data indicate B2R antagonists do not modulate physiologically-or pharmacologically-induced eccrine secretion volumes. Thus, B2R agonist/antagonist development as a potential therapeutic target for hypo- and hyperhidrosis appears unwarranted.

scholarly journals The Importance of Mimicking Dermal-Epidermal Junction for Skin Tissue Engineering: A Review

2021 ◽  
Vol 8 (11) ◽  
pp. 148
Author(s):  
Mina Aleemardani ◽  
Michael Zivojin Trikić ◽  
Nicola Helen Green ◽  
Frederik Claeyssens
Keyword(s):  
Tissue Engineering ◽  
Cell Function ◽  
Multiple Roles ◽  
Primary Role ◽  
Skin Substitutes ◽  
Anatomical Structures ◽  
And Function ◽  
Bioengineered Skin ◽  
Physical Boundary

There is a distinct boundary between the dermis and epidermis in the human skin called the basement membrane, a dense collagen network that creates undulations of the dermal–epidermal junction (DEJ). The DEJ plays multiple roles in skin homeostasis and function, namely, enhancing the adhesion and physical interlock of the layers, creating niches for epidermal stem cells, regulating the cellular microenvironment, and providing a physical boundary layer between fibroblasts and keratinocytes. However, the primary role of the DEJ has been determined as skin integrity; there are still aspects of it that are poorly investigated. Tissue engineering (TE) has evolved promising skin regeneration strategies and already developed TE scaffolds for clinical use. However, the currently available skin TE equivalents neglect to replicate the DEJ anatomical structures. The emergent ability to produce increasingly complex scaffolds for skin TE will enable the development of closer physical and physiological mimics to natural skin; it also allows researchers to study the DEJ effect on cell function. Few studies have created patterned substrates that could mimic the human DEJ to explore their significance. Here, we first review the DEJ roles and then critically discuss the TE strategies to create the DEJ undulating structure and their effects. New approaches in this field could be instrumental for improving bioengineered skin substitutes, creating 3D engineered skin, identifying pathological mechanisms, and producing and screening drugs.

scholarly journals A Novel Composite Hydrogel Composed of Formic Acid-Decellularized Pepsin-Soluble Extracellular Matrix Hydrogel and Sacchachitin Hydrogel as Wound Dressing to Synergistically Accelerate Diabetic Wound Healing

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 538
Author(s):  
Chien-Ming Hsieh ◽  
Weu Wang ◽  
Ying-Hsuan Chen ◽  
Pu-Sheng Wei ◽  
Yu-Hsuan Liu ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Formic Acid ◽  
Cell Viability ◽  
Hair Follicles ◽  
Composite Hydrogel ◽  
Sweat Glands ◽  
Diabetic Wound ◽  
Porcine Skin ◽  
Diabetic Wound Healing

Extracellular matrix (ECM) hydrogel can create a favorable regenerative microenvironment and act as a promising dressing for accelerating the healing of diabetic wound. In this study, a simple and effective decellularization technique was developed and optimized to obtain acellular extracellular matrix (aECM) from porcine skin. It was found that decellularization at 30% formic acid for 72 h effectively decellularized porcine skin while retaining >75% collagen and ~37% GAG in the aECM with no presence of nuclei of cellular remnants. aECM hydrogel was fabricated by digesting aECM with pepsin in various acidic solutions (0.1 N HCl, glycolic acid (GA) and 2-pyrrolidone-5-carboxylic acid (PCA)) and then treated with a pH-controlled neutralization and temperature-controlled gelation procedure. Based on physical characterizations, including SDS-PAGE, rheological analysis and SEM analysis, aECMHCl hydrogels fabricated at 25 mg/mL in 0.1 N HCl were selected. Four polymeric ECM-mimic hydrogels, including sacchachitin (SC), hyaluronic acid (HA) and chitosan (CS) and three composite hydrogels of combining SC either with aECMHCl,25 (aECMHCl/SC), HA (HA/SC) or CS (SC/CS) were prepared and evaluated for WS-1 cell viability and wound-healing effectiveness. Cell viability study confirmed that no hydrogel dressings possessed any toxicity at all concentrations examined and ECMHCl, HA and ECMHCl/SC at higher concentrations (>0.05%) induced statistically significant proliferation. Diabetic wound healing study and histological examinations revealed that ECMHCl/SC hydrogel was observed to synergistically accelerate wound healing and ultimately stimulated the growth of hair follicles and sweat glands in the healing wound indicating the wound had healed as functional tissues. The results support the great potential of this newly produced ECMHCl/SC composite hydrogel for healing and regeneration of diabetic wounds.

scholarly journals Regeneration of Dermis: Scarring and Cells Involved

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 607 ◽  
Author(s):  
Alexandra L. Rippa ◽  
Ekaterina P. Kalabusheva ◽  
Ekaterina A. Vorotelyak
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Hair Follicle ◽  
Scar Formation ◽  
Population Characteristics ◽  
Matrix Composition ◽  
Skin Substitutes ◽  
Skin Repair ◽  
Dermal Cell

There are many studies on certain skin cell specifications and their contribution to wound healing. In this review, we provide an overview of dermal cell heterogeneity and their participation in skin repair, scar formation, and in the composition of skin substitutes. The papillary, reticular, and hair follicle associated fibroblasts differ not only topographically, but also functionally. Human skin has a number of particular characteristics that are different from murine skin. This should be taken into account in experimental procedures. Dermal cells react differently to skin wounding, remodel the extracellular matrix in their own manner, and convert to myofibroblasts to different extents. Recent studies indicate a special role of papillary fibroblasts in the favorable outcome of wound healing and epithelial-mesenchyme interactions. Neofolliculogenesis can substantially reduce scarring. The role of hair follicle mesenchyme cells in skin repair and possible therapeutic applications is discussed. Participation of dermal cell types in wound healing is described, with the addition of possible mechanisms underlying different outcomes in embryonic and adult tissues in the context of cell population characteristics and extracellular matrix composition and properties. Dermal white adipose tissue involvement in wound healing is also overviewed. Characteristics of myofibroblasts and their activity in scar formation is extensively discussed. Cellular mechanisms of scarring and possible ways for its prevention are highlighted. Data on keloid cells are provided with emphasis on their specific characteristics. We also discuss the contribution of tissue tension to the scar formation as well as the criteria and effectiveness of skin substitutes in skin reconstruction. Special attention is given to the properties of skin substitutes in terms of cell composition and the ability to prevent scarring.

scholarly journals Development of an animal-free methodology for mechanical performance assessment of engineered skin substitutes

2020 ◽  
Author(s):  
Alessandra Aldieri ◽  
Mara Terzini ◽  
Diana Massai ◽  
Cristina Bignardi ◽  
Alberto Audenino
Keyword(s):  
Mechanical Behavior ◽  
Mechanical Performance ◽  
Animal Experiments ◽  
Skin Wounds ◽  
Skin Substitutes ◽  
Skin Tissue Engineering ◽  
Native Tissue ◽  
Biaxial Tests ◽  
Human Dermis ◽  
Constitutive Parameters

Functional substitutes for the treatment of skin wounds are nowadays widely available thanks to the progress in skin tissue engineering. However, the performance of the existing substitutes in terms of mechanical behavior, which is a determinant for their success, still does not match the native tissue. Since the mechanical behavior of skin is governed by dermis, an in-depth investigation of human dermis mechanics would be pivotal for integrating the design and validation of skin substitutes. In the perspective of reducing and replacing animal experiments through validated alternative tools, an accurate in silico constitutive model describing the human dermis mechanics is presented. Biaxial tests were performed on human dermis samples, and resulting data were used for setting the constitutive parameters of the model, able to reliably describing the mechanical properties of the native tissue, and to be compared with the mechanical behavior of skin substitutes attainable through the same procedure.

scholarly journals Scratch-induced partial skin wounds re-epithelialize by sheets of independently migrating keratinocytes

2020 ◽  
Vol 4 (1) ◽  
pp. e202000765
Author(s):  
Laura Bornes ◽  
Reinhard Windoffer ◽  
Rudolf E Leube ◽  
Jessica Morgner ◽  
Jacco van Rheenen
Keyword(s):  
Intravital Microscopy ◽  
Skin Barrier ◽  
Cell Loss ◽  
Hair Follicles ◽  
Migration Pattern ◽  
Sweat Glands ◽  
Skin Wounds ◽  
Wound Model ◽  
Scratch Wound ◽  
Suprabasal Keratinocytes

Re-epithelialization is a crucial process to reestablish the protective barrier upon wounding of the skin. Although this process is well described for wounds where the complete epidermis and dermis is damaged, little is known about the re-epithelialization strategy in more frequently occurring smaller scratch wounds in which structures such as the hair follicles and sweat glands stay intact. To study this, we established a scratch wound model to follow individual keratinocytes in all epidermal layers in the back skin of mice by intravital microscopy. We discover that keratinocytes adopt a re-epithelialization strategy that enables them to bypass immobile obstacles such as hair follicles. Wound-induced cell loss is replenished by proliferation in a distinct zone away from the wound and this proliferation does not affect overall migration pattern. Whereas suprabasal keratinocytes are rather passive, basal keratinocytes move as a sheet of independently migrating cells into the wound, thereby constantly changing their direct neighboring cells enabling them to bypass intact obstacles. This re-epithelialization strategy results in a fast re-establishment of the protective skin barrier upon wounding.

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