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Dermis

The dermis is the dense, fibrous layer of connective tissue that forms the middle region of the skin, situated directly beneath the epidermis and above the subcutaneous hypodermis, providing essential structural support, elasticity, and nourishment to the overlying epidermal cells. Composed primarily of an extracellular matrix rich in collagen (types I and III) and elastic fibers, along with ground substance such as glycosaminoglycans, the dermis originates from mesenchymal tissue and varies in thickness from approximately 1 to 4 mm across different body regions.^[1]^[2] Structurally, the dermis is divided into two main layers: the superficial papillary dermis, which consists of loose connective tissue with fine collagen and elastin fibers arranged in a network that facilitates nutrient exchange and houses capillary loops; and the deeper reticular dermis, comprising dense irregular connective tissue that forms the bulk of the layer and contains thicker bundles of collagen for tensile strength. Key components embedded within the dermis include blood vessels and lymphatics for circulation, sensory nerve endings such as Meissner's and Pacinian corpuscles for touch and pressure detection, hair follicles, sebaceous and sweat glands, and immune cells like mast cells and histiocytes. The primary cellular resident, fibroblasts, synthesizes and maintains the extracellular matrix, while adipocytes may appear in thinner regions.^[1]^[2]^[3] Functionally, the dermis plays a critical role in protecting deeper tissues from mechanical stress, aiding thermoregulation through vasoactive blood vessels and specialized glomus bodies that control heat dissipation, and enabling sensory perception via its network of mechanoreceptors and nociceptors. It also supports wound healing by providing a scaffold for epidermal regeneration and contributes to immune defense through resident leukocytes. These attributes make the dermis indispensable for skin integrity and overall homeostasis, with disruptions often leading to conditions like dermal atrophy or fibrosis.^[1]^[3]^[2]

Overview

Definition and location

The dermis is the middle layer of the skin, a dense connective tissue structure that lies beneath the epidermis and provides essential mechanical support to the integumentary system by anchoring the outer skin layer and contributing to overall skin resilience.^[1] Composed primarily of fibrous elements, it serves as the foundational framework for skin integrity, enabling the organ to withstand physical stresses.^[4] Anatomically, the dermis is positioned directly below the epidermis, to which it attaches via a basement membrane, and above the subcutaneous hypodermis, forming a transitional zone that integrates the skin's protective and supportive functions.^[5] Its thickness varies significantly across body regions, typically ranging from 0.5 mm to 4 mm, with the thinnest areas occurring on the eyelids (around 0.5 mm) and the thickest on the back (up to 4 mm); palms and soles are also relatively thick.^[6]^[7]^[8] These regional differences in dermal thickness correlate with the skin's adaptive needs in areas exposed to varying levels of mechanical demand and environmental exposure.^[2] The term "dermis" originates from the New Latin form of the Ancient Greek word derma, meaning "skin" or "hide," reflecting its role as the "true skin" beneath the surface layer.^[9]

General composition

The dermis is primarily composed of dense irregular connective tissue, featuring a sparse population of cells embedded within a robust extracellular matrix (ECM). This arrangement provides structural support and flexibility to the skin. The ECM forms the predominant structural framework, comprising interwoven fibers and an amorphous ground substance that fills the intercellular spaces.^[1]^[10] In terms of volume, the ECM accounts for approximately 90% of the dermis, while cellular components represent about 10%, highlighting the acellular dominance that defines its mechanical properties. The ground substance within the ECM is rich in glycosaminoglycans (GAGs), which contribute to hydration and resilience, constituting 0.1–0.3% of the total skin weight with a higher concentration in the dermis compared to the epidermis.^[1]^[11]^[12] Additionally, the dermis houses essential vascular and neural elements, including blood vessels that supply nutrients and oxygen, lymphatic vessels that aid in fluid balance, and nerves that transmit sensory information. Skin appendages such as hair follicles and glands are also integrated within this matrix, contributing to its overall functionality without altering its connective tissue core. The dermis consists of two main layers: the superficial papillary dermis, which is looser in structure, and the deeper reticular dermis, which is denser.^[8]^[13]^[1]

Anatomical layers

Papillary dermis

The papillary dermis is the uppermost layer of the dermis, situated immediately beneath the epidermis and forming the interface between the two primary skin strata. It consists of loose areolar connective tissue, characterized by a network of fine collagen fibers (primarily types I and III) and thinner elastic fibers, which contribute to its flexible and pliable nature. This layer typically measures 0.1 to 0.3 mm in thickness, accounting for approximately 10 to 20% of the total dermal volume, with variations depending on body region—thinner on areas like the eyelids and thicker on the palms.^[1]^[14]^[15] A defining feature of the papillary dermis is the presence of dermal papillae, which are finger-like projections of connective tissue that extend upward into the overlying epidermis, interdigitating with the epidermal rete ridges. These papillae significantly increase the surface area of contact between the dermis and epidermis, enhancing mechanical adhesion and facilitating efficient nutrient and oxygen exchange. The high vascularity of this layer, marked by a dense network of capillaries within the papillae and a superficial subpapillary plexus, supports its role in nourishing the avascular epidermis through diffusion from capillary loops.^[1]^[15] In contrast to the denser reticular dermis below, the papillary dermis's loose structure allows for greater permeability and metabolic activity at the epidermal junction, optimizing its supportive and nutritive functions.^[1]

Reticular dermis

The reticular dermis constitutes the deeper and thicker portion of the dermis, situated immediately below the papillary dermis and above the hypodermis. It accounts for approximately 80% of the total dermal volume and exhibits a thickness ranging from 1 to 3 mm, varying by anatomical location such as greater depth on the back compared to thinner regions like the eyelids.^[16]^[6]^[2] This layer is composed of dense irregular connective tissue, featuring coarse bundles of primarily type I and type III collagen fibers arranged in a interwoven network that imparts significant mechanical strength and durability to the skin. Elastic fibers, including elaunin fibers, are interspersed among the collagen, providing resilience, though they are less abundant relative to the dominant collagen components. In contrast to the overlying papillary dermis, the reticular dermis lacks dermal papillae and instead incorporates larger vascular structures, such as blood vessels and nerves, along with glandular elements like sweat and sebaceous glands.^[1]^[6] The reticular dermis transitions gradually into the hypodermis through a progressive coarsening of its collagen fibers, which extend without a sharp demarcation into the underlying subcutaneous adipose tissue. Hair follicles and other skin appendages are anchored within this layer, enhancing overall dermal stability.^[6]^[1]

Cellular components

Fibroblasts and other resident cells

Fibroblasts represent the predominant cell type in the dermis, serving as the primary architects of the skin's structural integrity. These mesenchymal cells exhibit a characteristic spindle-shaped morphology with elongated cytoplasmic processes, enabling them to navigate and interact within the extracellular matrix (ECM).^[17]^[18] Their core function involves the synthesis and maintenance of key ECM components, including collagen fibers (predominantly types I and III), elastin, and proteoglycans such as decorin and biglycan, which collectively provide tensile strength, elasticity, and hydration to the dermal layer.^[19]^[20] A specialized variant of fibroblasts, known as myofibroblasts, emerges particularly during tissue repair processes. These cells acquire contractile properties through the expression of alpha-smooth muscle actin (α-SMA) and prominent actin-myosin filaments, allowing them to generate mechanical tension that facilitates wound closure and ECM remodeling.^[18]^[19] While quiescent fibroblasts maintain homeostasis, myofibroblasts represent a transient, activated state induced by environmental cues like mechanical stress.^[20] Beyond fibroblasts, other resident cells contribute to dermal architecture. Adipocytes, though present in smaller numbers, are notably found in the upper papillary dermis, where they provide mechanical cushioning and support epidermal structures.^[21] Mast cells also reside within the dermis, embedded in the connective tissue to help stabilize the local environment through their granular contents.^[22] Cell density varies by dermal layer, with the papillary dermis exhibiting a higher concentration of fibroblasts in a looser arrangement compared to the denser packing in the reticular dermis.^[23]

Immune cells

The dermis harbors a diverse population of immune cells that form a resident network essential for local immune surveillance and response, distinct from epidermal components. Key resident immune cells include macrophages, dendritic cells, lymphocytes, and mast cells, which collectively contribute to both innate and adaptive immunity in the skin.^[24] These cells are replenished from bone marrow precursors and maintain homeostasis while responding to threats such as pathogens or allergens.^[22] Macrophages, the most abundant hematopoietic cells in steady-state dermis, perform phagocytosis to clear debris and pathogens, and release cytokines such as IL-1β, TNF-α, and IL-6 to orchestrate inflammation and tissue repair.^[24]^[22] Dendritic cells, specialized antigen-presenting cells, capture and process antigens in the dermis, migrating to draining lymph nodes to initiate adaptive immune responses by activating T cells; subsets like CD301b+ dendritic cells promote Th2-biased responses relevant to allergic contexts.^[25]^[22] Lymphocytes, primarily T cells including CD4+ and γδ subsets, mediate adaptive immunity through cytokine production (e.g., IFN-γ, IL-17) and direct cytotoxicity, with γδ T cells providing rapid innate-like defense against skin infections.^[24] Mast cells, enriched near dermal appendages, degranulate to release histamine and cytokines like TNF-α upon IgE cross-linking, amplifying immediate hypersensitivity reactions.^[25]^[22] In terms of density and distribution, immune cells are more concentrated in the papillary dermis for enhanced surveillance of the skin surface, with macrophages and dendritic cells showing higher prevalence there compared to the reticular dermis, which supports broader leukocyte infiltration during responses.^[22] Overall, lymphocytes constitute approximately 40% of dermal immune cells, macrophages about 10%, dendritic cells around 15% within myeloid populations, and mast cells form a significant resident pool estimated at 7,000 per gram of dermis tissue in normal skin, increasing with age.^[26]^[22] This layered distribution facilitates rapid detection in superficial layers while allowing escalation in deeper tissues. These cells contribute to dermal inflammation by recruiting and activating additional leukocytes through chemokine gradients and cytokine signaling, with macrophages and dendritic cells driving pro-inflammatory cascades.^[24] In allergic responses, mast cells play a central role in conditions like urticaria, where IgE-mediated degranulation triggers histamine release, leading to vascular permeability and wheal formation, often in concert with eosinophil infiltration.^[25]^[22] Interaction with the dermal vasculature is crucial for immune function, as perivascular macrophages and mast cells regulate leukocyte extravasation at post-capillary venules by secreting chemokines and growth factors like VEGF, facilitating recruitment of circulating monocytes, neutrophils, and T cells during inflammation.^[24]^[22] Dendritic cells and mast cells further enhance this by forming synapses that transfer antigens and signals, promoting coordinated responses.^[25]

Extracellular matrix

Collagen fibers

Collagen fibers constitute the predominant component of the dermal extracellular matrix, comprising approximately 70-80% of its dry weight and providing essential structural integrity to the skin.^[27] In the human dermis, type I collagen is the most abundant, accounting for 80-90% of total collagen content, and forms thick fibrils that confer high tensile strength to withstand mechanical stresses.^[27] Type III collagen, making up about 5-15%, consists of thinner fibrils primarily located in the papillary dermis, contributing to tissue flexibility and early wound healing responses.^[28] These two types together form a hierarchical network of fibers that interweave with elastin to enable skin recoil after deformation.^[29] Structurally, collagen molecules are composed of three polypeptide chains arranged in a triple-helix configuration, which self-assemble extracellularly into fibrils with diameters ranging from 50 to 200 nm.^[30] These fibrils are further stabilized by enzymatic cross-links formed through the action of lysyl oxidase, an enzyme that oxidizes lysine residues to create covalent bonds, enhancing fibril rigidity and resistance to degradation.^[31] Dermal fibroblasts are the primary cells responsible for collagen synthesis, producing procollagen precursors that are processed and assembled outside the cell.^[28] This process is tightly regulated by transforming growth factor-β (TGF-β) signaling, which upregulates collagen gene expression and promotes fibril assembly in response to mechanical or injury-related cues.^[32] Biomechanically, collagen fibers in the dermis exhibit a Young's modulus of approximately 1-10 MPa, reflecting their role in balancing tensile strength and elasticity to accommodate skin stretching and deformation without rupture.^[33]

Elastin and ground substance

Elastin constitutes 2–4% of the extracellular matrix (ECM) in the adult human dermis, forming an intricate network of amorphous elastic fibers that provide resilience to the skin. These fibers are primarily composed of tropoelastin, a soluble precursor protein that undergoes cross-linking via lysyl oxidase-mediated desmosine bonds to create insoluble, highly elastic structures organized into fibers and lamellae. This architecture enables the dermis to undergo substantial deformation, with elastin fibers supporting stretch and recoil capabilities of up to 100% or more, allowing full recovery without permanent deformation.^[34]^[35]^[36] In the dermis, elastin is more abundant in the deeper reticular layer, where it forms a three-dimensional meshwork oriented both parallel and perpendicular to the skin surface, contributing to overall tissue flexibility. Its distribution decreases with age, as elastin synthesis by fibroblasts diminishes after puberty, leading to fragmentation and reduced elasticity over time due to limited turnover and environmental degradation.^[34]^[35] The ground substance of the dermal ECM, an amorphous gel-like medium, is primarily composed of glycosaminoglycans (GAGs) such as hyaluronic acid and chondroitin sulfate, along with proteoglycans and glycoproteins, which fill the spaces between elastic and other fibers. Hyaluronic acid, a key nonsulfated GAG, exhibits exceptional hydrophilic properties, capable of binding up to 1,000 times its weight in water to maintain dermal hydration and turgor. Proteoglycans, such as decorin and biglycan, further enhance this by forming complexes that regulate water retention and molecular interactions within the ECM.^[1]^[37] Functionally, the ground substance facilitates the diffusion of nutrients, ions, and metabolites through the avascular dermis by providing a hydrated, low-viscosity environment that supports solute transport and tissue homeostasis. Elastin fibers integrate with the surrounding ground substance and other ECM components to confer viscoelastic properties to the dermis, where the elastic recoil of elastin balances hydration-mediated lubrication for dynamic skin movement.^[1]^[37]^[34]

Functions

Structural support

The dermis serves as the primary structural foundation of the skin, conferring mechanical integrity through its dense network of extracellular matrix components, particularly collagen and elastin fibers. This framework enables the skin to withstand everyday physical stresses without compromising its barrier function.^[1]^[38] Tensile strength is predominantly provided by the collagen network, which forms a robust scaffold of type I and type III fibers that resists tearing and deformation under mechanical load. In the reticular dermis, these densely packed collagen fibrils align and reorganize in response to tension, blunting stress concentrations and preventing crack propagation, as observed in studies of skin's tear resistance mechanisms.^[1]^[39] This property is essential for maintaining skin cohesion during activities involving stretching or impact. Elasticity arises from elastin fibers, which constitute 2–4% of the dermis's dry mass and form a three-dimensional meshwork that allows for reversible deformation and rapid recoil. Elastin operates at low strains with a Young's modulus of 0.1–1.5 MPa, enabling the skin to stretch during movement—such as joint flexion—and return to its original shape, complementing collagen's higher-modulus resistance at greater loads.^[35]^[1] The dermis anchors the epidermis via the dermal-epidermal junction, a corrugated interface featuring rete ridges and dermal papillae that enhance adhesion through hemidesmosomes and basement membrane proteins like collagen IV and laminin. This anchorage resists shear forces, particularly in high-friction areas like palms and soles, where deepened ridges increase mechanical interlock and prevent delamination.^[40] Similarly, the dermis embeds and supports skin appendages such as hair follicles and glands, securing them against displacement from external forces.^[1]^[38] Overall, these mechanical attributes contribute to the skin's barrier against trauma by distributing forces across the tissue, protecting underlying structures from abrasion, puncture, and excessive strain. The extracellular matrix's composition, including collagen and elastin, underpins this resilience without delving into its detailed components.^[1]^[39]

Sensory and vascular roles

The dermis plays a crucial role in sensory perception through its extensive innervation by somatosensory nerves. Free nerve endings, primarily associated with Aδ and C fibers, are distributed throughout the dermis and detect pain, temperature changes, and crude touch stimuli.^[41] These unmyelinated or thinly myelinated endings respond to mechanical pressure, thermal variations, and noxious stimuli, transmitting signals to the central nervous system for protective reflexes and awareness.^[42] Encapsulated mechanoreceptors further enhance tactile discrimination within specific dermal layers. Meissner corpuscles, located in the papillary dermis beneath the epidermal ridges of glabrous skin such as the fingers, palms, and soles, serve as rapidly adapting receptors for low-frequency vibrations and light touch, enabling fine discrimination of textures and object manipulation.^[42] In contrast, Pacinian corpuscles reside deeper in the reticular dermis and subcutaneous tissue, functioning as rapidly adapting sensors for high-frequency vibrations (around 200-300 Hz) and deep pressure, with their onion-like lamellar structure filtering rapid mechanical deformations to detect subtle movements like those from machinery or impacts.^[42] The vascular network of the dermis ensures vital nutrient and oxygen delivery to the overlying avascular epidermis while supporting dermal homeostasis. In the papillary dermis, arterioles (10-100 μm in diameter) give rise to capillary loops that ascend into the dermal papillae and drain into postcapillary venules (10-200 μm), forming a superficial horizontal plexus at the epidermal-dermal junction.^[43] This arrangement allows for efficient diffusion of oxygen and nutrients across the thin epidermal barrier (0.06-0.6 mm thick), with capillary densities ranging from 16-65 per mm² to meet metabolic demands without excessive vascularization.^[43] Deeper in the reticular dermis, a more robust horizontal plexus of larger arterioles and venules supplies the bulkier connective tissue, hair follicles, and glands, facilitating waste removal and maintaining tissue viability over the dermis's 1-4 mm thickness.^[43] Beyond basic perfusion, the dermal vasculature contributes to thermoregulation through specialized structures. Arteriovenous anastomoses, direct connections between arterioles and venules bypassing the capillary bed, are concentrated in acral skin regions like the hands and feet; their dilation, mediated by reduced sympathetic tone from the hypothalamus, increases cutaneous blood flow up to 8 L/min, promoting radiative and convective heat loss that accounts for about 60% of total body heat dissipation.^[44] The dermis also supports eccrine sweat glands embedded within its layers, which, upon cholinergic activation, secrete hypotonic fluid for evaporative cooling (contributing ~22% of heat loss), with vascular plexuses providing the necessary hydration and nutrients to sustain glandular function during prolonged thermal stress.^[44] Lymphatic vessels in the dermis maintain fluid balance and immune surveillance by draining interstitial fluid and facilitating cellular transport. Initial lymphatic capillaries, blind-ended and highly permeable, originate in the papillary dermis and collect excess interstitial fluid (~3 L/day) that escapes the vascular system, propelling it unidirectionally via intrinsic contractions and extrinsic compression toward collecting vessels in the reticular dermis.^[45] These lymphatics also transport immune cells, such as dendritic cells and lymphocytes, from peripheral tissues to draining lymph nodes, enabling antigen presentation and adaptive immune responses while preventing edema accumulation.^[45]

Development and maintenance

Embryonic development

The dermis arises primarily from mesodermal tissues during early embryogenesis, with contributions from the lateral plate mesoderm forming the dermis in the limbs and ventral regions, paraxial mesoderm contributing to the dorsal and trunk dermis, and neural crest cells supplying the craniofacial dermis.^[46]^[47] These mesenchymal precursors undergo epithelial-to-mesenchymal transition and migrate to underlie the developing epidermis, establishing the foundational connective tissue layer.^[48] Histological distinction of the dermis emerges as early as the sixth week of embryonic development, coinciding with the initial migration of fibroblasts into the subepidermal space.^[47] By the eighth week, fibroblast proliferation intensifies, accompanied by the onset of extracellular matrix (ECM) deposition, including early collagen and proteoglycan synthesis that provides initial structural support.^[49] This timeline aligns with the broader organogenesis phase, where the dermis transitions from a loose mesenchymal aggregate to a more organized tissue. Differentiation into papillary and reticular layers begins in the embryonic period, with the papillary dermis forming first from the subjacent mesenchyme through localized fibroblast condensation and fine collagen network assembly.^[50] The reticular dermis develops subsequently, driven by progressive accumulation of thicker collagen bundles produced by maturing fibroblasts, establishing the denser framework observed later in fetal stages.^[49] Epidermal-dermal interactions are crucial for dermal patterning, mediated by inductive signals from the overlying epidermis that promote mesenchymal condensation and ECM organization.^[51] Key pathways include Wnt signaling, which orchestrates reciprocal communication to specify dermal cell fates, and BMP signaling, which regulates fibroblast differentiation and collagen deposition in response to epidermal cues.^[52]^[53] These molecular exchanges ensure coordinated development, preventing disorganized tissue formation.

Postnatal changes and repair

After birth, the dermis undergoes adaptive changes influenced by hormonal fluctuations. Estrogen plays a key role in maintaining dermal hydration by stimulating hyaluronic acid synthesis, which enhances water retention and supports skin elasticity.^[54] In contrast, androgens contribute to increased dermal thickness, particularly evident in gender-specific differences that emerge post-puberty, where higher androgen levels promote collagen deposition and overall dermal density.^[55] These hormonal effects help transition the dermis from its embryonic state to a mature structure capable of responding to environmental stresses. With advancing age, the dermal extracellular matrix experiences progressive degradation, leading to structural weakening. Collagen production declines by approximately 1% annually after the mid-20s, resulting in net loss and fragmentation of fibrils, which reduces skin firmness and contributes to wrinkle formation.^[56] Elastin fibers also degrade over time due to enzymatic breakdown and oxidative damage, diminishing the dermis's recoil properties and exacerbating sagging.^[34] These changes are driven by downregulated transforming growth factor-β signaling and elevated matrix metalloproteinases, altering the dermal microenvironment to impair mechanical integrity.^[57] Dermal repair, particularly through wound healing, occurs in overlapping phases that restore tissue integrity. The inflammatory phase, lasting several days, involves immune cell influx—primarily neutrophils and macrophages—for debris clearance and pathogen defense, mediated by platelet-derived growth factors and cytokines.^[58] This transitions to the proliferative phase over weeks, where fibroblasts synthesize extracellular matrix components like collagen and glycosaminoglycans, while angiogenesis forms new vessels to support granulation tissue.^[58] Myofibroblasts, differentiated from fibroblasts, drive wound contraction through actin-mediated traction on the matrix.^[59] In the remodeling phase, spanning months, collagen cross-links strengthen the scar, though tensile strength reaches only about 80% of uninjured dermis.^[58] Excessive myofibroblast activity, however, can lead to fibrosis, characterized by overproduction of disorganized extracellular matrix and persistent contraction.^[60] Hormonal modulation influences these processes, with estrogen enhancing overall healing efficiency by promoting angiogenesis and reducing inflammation.^[61]

Clinical significance

Common disorders

The dermis, the supportive layer beneath the epidermis, is implicated in various genetic disorders that compromise its structural integrity. Ehlers-Danlos syndrome (EDS) encompasses a group of heritable connective tissue disorders primarily arising from defects in collagen synthesis or structure, leading to dermal fragility, hyperextensible skin, and impaired wound healing.^[62] These collagen abnormalities weaken the extracellular matrix of the dermis, resulting in easy bruising, atrophic scarring, and increased susceptibility to trauma.^[63] Cutis laxa represents another genetic condition characterized by elastin deficiency or disruptions in elastic fiber assembly within the dermis, manifesting as loose, sagging, and inelastic skin that hangs in folds.^[64] This elastin shortfall reduces the dermis's recoil properties, often leading to premature aging-like appearance and potential internal organ involvement.^[65] Inflammatory disorders frequently target the dermis through immune dysregulation, altering its barrier and inflammatory responses. Atopic dermatitis, a chronic immune-mediated condition, disrupts the dermal-epidermal barrier via T-cell driven inflammation, causing dermal edema, pruritus, and lichenification in chronic cases.^[66] This leads to impaired dermal hydration and increased allergen penetration, perpetuating a cycle of inflammation.^[67] Psoriasis, another immune-mediated dermatosis, involves dermal infiltration by neutrophils, T lymphocytes, and macrophages, resulting in papillary dermal angiogenesis and spongiform pustules that extend into the dermis.^[68] These changes manifest as erythematous plaques with scaling, driven by cytokine release such as IL-17 and IL-23 from dermal immune cells.^[69] Infectious processes can invade the dermis, leading to acute or chronic pathology. Cellulitis is an acute bacterial infection, typically by Streptococcus or Staphylococcus species, that spreads through the deep dermis and subcutaneous tissue, causing erythema, warmth, and swelling due to bacterial proliferation and host inflammatory response.^[70] Leprosy, caused by Mycobacterium leprae, induces perineural granulomatous inflammation in the dermis, damaging small dermal nerves and leading to sensory loss, hypopigmented patches, and eventual dermal atrophy.^[71] This nerve involvement in the dermis contributes to trophic ulcers and deformities over time.^[72] Globally, inflammatory dermal disorders like atopic dermatitis affect 10-20% of children and up to 3% of adults, highlighting their significant public health burden.^[73] Genetic conditions such as EDS and cutis laxa are rarer, with incidences around 1 in 5,000 and 1 in 1,000,000, respectively, underscoring the spectrum from common to exceptional dermal pathologies.^[62]^[64]

Aging and pathology

As individuals age, the dermis undergoes progressive structural alterations that compromise its integrity. Collagen content diminishes by approximately 1% annually after the mid-20s, leading to reduced dermal thickness and elasticity.^[74] Elastin fibers fragment and degrade, resulting in diminished recoil and sagging.^[75] Additionally, glycosaminoglycans (GAGs) decrease, impairing water retention and contributing to skin dryness.^[76] Functional declines in the aging dermis further exacerbate these changes. Wound healing is impaired due to slower angiogenesis and reduced vascularization, prolonging recovery times.^[77] Sensory perception diminishes as nerve endings in the dermis decrease, leading to reduced tactile sensitivity.^[78] Vascular fragility increases, making dermal blood vessels more prone to rupture and bruising.^[79] Photoaging, driven by chronic ultraviolet (UV) exposure, accelerates dermal pathology through upregulation of matrix metalloproteinases (MMPs), which degrade the extracellular matrix (ECM).^[80] This UV-induced ECM breakdown not only intensifies wrinkling and laxity but also heightens the risk of skin cancers, such as squamous cell carcinoma, by promoting mutagenic inflammation.^[81] Gender-specific differences emerge post-menopause, when estrogen decline accelerates dermal thinning in women, with collagen loss reaching up to 2% per year and overall skin thickness reducing by about 1.13% annually.^[82]

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Age-dependent biomechanical properties of the skin - PMC - NIH
In the literature, the Young's modulus (E) of the skin fluctuates between 0.42 MPa and 0.85 MPa [1, 20] for the torsion tests, between 4.6 MPa and 20 MPa [21] ...
[34]
Clinical Relevance of Elastin in the Structure and Function of Skin
May 14, 2021 · For example, the dermal reticular and papillary layers contain elastic fibers that differ in their thickness, orientation, and relative ...
[35]
Mechanical Properties and Functions of Elastin: An Overview - NIH
Mar 22, 2023 · Its function is to endow soft tissues with low stiffness, high and fully reversible extensibility, and efficient elastic–energy storage.
[36]
Elastin Structure, Synthesis, Regulatory Mechanism and ... - Frontiers
Nov 29, 2021 · This review article summarizes the role of elastin in myocardial ischemia-reperfusion, atherosclerosis, and atrial fibrillation, with emphasis on the potential ...
[37]
Skin Viscoelasticity: Physiologic Mechanisms, Measurement Issues ...
GAGs, such as hyaluronic acid, are hydrophilic polysaccharide chains that bind with water in volumes up to 1,000 times their own, expanding the extracellular ...Missing: capacity | Show results with:capacity
[38]
Skin Health | Linus Pauling Institute | Oregon State University
However, nearly 75% of the weight of the dermis is a matrix of collagen, an extracellular protein that allows for both structural support and elasticity of the ...
[39]
Skin Tough - Berkeley Lab News Center
Mar 31, 2015 · Mechanical properties are largely determined in the dermis, which is the thickest layer and is made up primarily of collagen and elastin ...
[40]
The Importance of Mimicking Dermal-Epidermal Junction for Skin ...
This region has interdigitated topography that results in an increment in mechanical shear resistance, paracrine diffusion, and surface area between the dermis ...
[41]
Neuroscience for Kids - Receptors
Dermis of glabrous skin. Free nerve endings, A-delta and C, Different types of free nerve endings that respond to mechanical, thermal or noxious stimulation.
[42]
Physiology, Mechanoreceptors - StatPearls - NCBI Bookshelf
Meissner's corpuscles are encapsulated neurons between the dermal papillae under the epidermis of the glabrous skin on the fingers, palms, and soles - ...
[43]
Microvascular Imaging of the Skin - PMC - NIH
Shown are the capillary loops and smaller arterioles and venules of the papillary plexus, and the deeper, larger arterioles and venules of the reticular plexus.
[44]
Physiology, Heat Loss - StatPearls - NCBI Bookshelf
Vasodilation results in the opening of arterioles and arteriovenous anastomoses ... Sweat glands have muscarinic receptors activated by acetylcholine to enhance ...
[45]
Overcoming transport barriers for interstitial-, lymphatic-, and lymph ...
The lymphatic vasculature transports interstitial fluid and solutes to lymph nodes in a unidirectional fashion, regulating tissue fluid balance, immune cell ...
[46]
A developmental basis for the anatomical diversity of dermis in ... - NIH
The dermis has disparate embryonic origins; abdominal dermis develops from lateral plate mesoderm, dorsal dermis from paraxial mesoderm and facial dermis ...
[47]
Concise Review: Human Dermis as an Autologous Source of Stem ...
Aug 7, 2015 · Dermis is distinguished histologically as early as week 6 of human development [10]. During embryonic development, dermis is derived from ...
[48]
Neural crest and the origin of species‐specific pattern - PMC
Beneath the epidermis lies the dermis, which in the trunk and posterior regions of the head comes from mesodermal mesenchyme, whereas in the face and aspects of ...1. Introduction · Figure 2 · Figure 3
[49]
Fetal Fibroblast Heterogeneity Defines Dermal Architecture during ...
Fibroblasts corresponding to papillary dermis (GRP+) were predominant 9–13 weeks after conception, whereas reticular dermal fibroblasts (ASPN+) were the major ...Missing: timeline | Show results with:timeline
[50]
Fetal Fibroblast Heterogeneity Defines Dermal Architecture during ...
During human embryo development, organogenesis occurs from 3 through 8 weeks ... This analysis revealed 2 groups of skin samples that clustered according to ...Missing: timeline | Show results with:timeline
[51]
The Roles of WNT Signaling Pathways in Skin Development ... - NIH
Nov 24, 2023 · In the early stage of skin development, communication between the embryonic epidermis and dermis is essential for basement membrane formation, ...
[52]
BMP-FGF Signaling Axis Mediates Wnt-Induced Epidermal ...
Our findings identify an essential BMP-FGF signaling axis in the dermis that responds to the epidermal Wnts and feedbacks to regulate basal progenitors during ...
[53]
Concise Review: Wnt Signaling Pathways in Skin Development and ...
Oct 19, 2017 · At the early stages of skin development, dynamic signaling crosstalk occurs between the embryonic epidermis and the dermis. The inter-tissue ...
[54]
Effect of estrogens on skin aging and the potential role of SERMs - NIH
In mice, estrogen administration increased hyaluronic acid synthesis by 70% in two weeks (Sobel 1965), leading to increased dermal water content.
[55]
Androgens and ageing of the skin - PubMed
Amongst them, androgens display a distinguished role. They modulate epidermal and dermal thickness as proven in a variety of studies measuring gender-specific ...
[56]
Skin collagen through the lifestages: importance for skin health and ...
With age, the ability to replenish collagen naturally decreases by about 1.0%-1.5% per year. This decrease in collagen is one of the characteristic hallmarks ...<|separator|>
[57]
Role of Age-Associated Alterations of the Dermal Extracellular ...
During aging, dermal collagen fibrils undergo progressive loss and fragmentation, leading to thin and structurally weakened skin. Age-related alterations of ...
[58]
Wound Healing Phases - StatPearls - NCBI Bookshelf
This activity reviews the evaluation and treatment of wounds and discusses the various wound healing phases.
[59]
The Role of Myofibroblasts in Physiological and Pathological Tissue ...
Myofibroblasts are the construction workers of wound healing and repair damaged tissues by producing and organizing collagen/extracellular matrix (ECM) into ...Myofibroblasts 101 · Myofibroblast Origins · Myofibroblast Mechanical...
[60]
The myofibroblast matrix: implications for tissue repair and fibrosis
Myofibroblasts are the primary extracellular matrix (ECM)-secreting cells during wound healing and fibrosis, and are largely responsible for the contractility ...The Myofibroblast Matrix... · Fibrillins And Ltbps · Proteoglycans
[61]
Cutaneous manifestations of estrogen excess and deficiency
Dec 13, 2021 · Estrogens have a profound influence on the skin, modulating skin physiology and improving angiogenesis, wound healing and immune responses.
[62]
Ehlers-Danlos Syndrome - StatPearls - NCBI Bookshelf - NIH
Ehlers-Danlos syndrome (EDS) is a genetic disorder ... The underlying collagen abnormalities predispose the patient's skin to poor wound healing and dehiscence.
[63]
The Ehlers-Danlos syndrome: on beyond collagens - PMC - NIH
EDS is characterized in its most common form by hyperextensibility of the skin, hypermobility of joints often resulting in dislocations, and tissue fragility ...
[64]
Cutis Laxa - StatPearls - NCBI Bookshelf - NIH
Feb 29, 2024 · Cutis laxa, also known as elastolysis, encompasses a spectrum of rare connective tissue disorders characterized by lax, redundant, and/or inelastic skin, as ...
[65]
Autosomal recessive cutis laxa syndrome revisited - PMC
Cutis laxa is an acquired or inherited skin disorder characterized by wrinkled, inelastic skin. Inborn errors of elastin synthesis and structural defects of ...
[66]
Atopic Dermatitis: A Disease of Altered Skin Barrier and Immune ...
Atopic dermatitis (AD) is an important chronic or relapsing inflammatory skin disease that often precedes asthma and allergic disorders.Missing: dermis | Show results with:dermis
[67]
Significance of Skin Barrier Dysfunction in Atopic Dermatitis - PMC
Atopic dermatitis (AD) is the most common, complex chronic inflammatory skin disease. Skin barrier dysfunction is the initial step in the development of AD.Missing: dermis | Show results with:dermis
[68]
Psoriasis - StatPearls - NCBI Bookshelf - NIH
Psoriasis is a chronic proliferative and inflammatory condition of the skin. It is characterized by erythematous plaques covered with silvery scales.
[69]
Advances in the pathogenesis of psoriasis: from keratinocyte ...
Jan 24, 2022 · It is characterized by epidermal hyperplasia and dermal infiltration of immune cells. Here, we review the role of keratinocytes in the ...
[70]
Cellulitis - StatPearls - NCBI Bookshelf - NIH
It is an acute bacterial infection causing inflammation of the deep dermis and surrounding subcutaneous tissue. The infection is without an abscess or purulent ...
[71]
Nerve damage in leprosy: a continuing challenge to scientists ...
Nerve damage affects small dermal nerves and peripheral nerve trunks. Perineural inflammation is a characteristic and hallmark of early leprosy. T cell-mediated ...
[72]
Leprosy - StatPearls - NCBI Bookshelf - NIH
In cases involving lepromatous disease, the damage is more generalized. The involvement of nerve trunks of the body includes ulnar/median nerves, the peroneal ...
[73]
Atopic dermatitis: global epidemiology and risk factors - PubMed
AD affects up to 20% of children and up to 3% of adults; recent data show that its prevalence is still increasing, especially in low-income countries. First ...
[74]
Collagen: What It Is, Types, Function & Benefits - Cleveland Clinic
Type I. This type makes up 90% of your body's collagen. Type I is densely packed and used to provide structure to your skin, bones, tendons and ligaments. Type ...
[75]
Elastic fibers during aging and disease - ScienceDirect.com
Aging of elastin and elastic fibers involves enzymatic degradation, oxidative damage, glycation, calcification, aspartic acid racemization, binding of lipids ...
[76]
Intrinsic aging- and photoaging-dependent level changes of ...
These intrinsic aging- and photoaging-dependent GAG changes and their correlations with water content provide new insights into the pathophysiology of dry skin ...Missing: dryness | Show results with:dryness
[77]
Impaired angiogenesis in ageing: the central role of the extracellular ...
Jul 11, 2023 · An increasing number of studies have demonstrated that angiogenic capacity declines drastically with age. Wound healing occurs at a slower rate ...
[78]
Age-related changes in cutaneous sensation in the healthy human ...
Changes in the mechanics of the skin itself, including dehydration (Verrillo et al. 1998), may contribute to reduced sensation with age (Woodward 1993; Vega- ...
[79]
Aging changes in skin: MedlinePlus Medical Encyclopedia
Jul 15, 2024 · As you age, you are at increased risk for skin injury. Your skin is thinner, more fragile, and you lose some of the protective fat layer.
[80]
Matrix-degrading Metalloproteinases in Photoaging - PMC
UV irradiation induces expression of certain members of the matrix metalloproteinase (MMP) family, which degrade collagen and other extracellular matrix (ECM) ...
[81]
Review TGFβ Signaling in Photoaging and UV-Induced Skin Cancer
Although not usually considered a typical pathogenic event, photoaging affects facial appearance and skin function and increases the risk of skin carcinogenesis ...
[82]
Estrogens and aging skin - PMC - NIH
Many of these effects can be reversed by estrogen replacement which increases epidermal hydration, skin elasticity and skin thickness as well as reducing ...