I. Concept of scar
Scar (scar) is an inevitable product of the healing process of trauma. There are two forms of wound healing, one is complete repair, i.e. repair by cells with the same structure as the original injured tissue, such as the non-scarring healing of early fetal wounds, or the healing of superficial wounds; otherwise almost all wounds end in scarring while epithelialising. This scar is a product of the normal tissue repair process and is therefore called a “normalscar”. When the repair process is abnormal, a large amount of extracellular matrix, mainly collagen, is deposited and an overgrowth of dermal tissue occurs, resulting in a “pathological scar” (abnormalscar), which is called a “hypertrophic scar” (hypertrophicscar). hypertrophicscar (HS) or “keloid” (K). Hypertrophic scars and keloids are a group of dermatofibrotic diseases, like thoracic or abdominal adhesive lesions, cirrhosis of the liver, pulmonary fibrosis, etc. They are pathological conditions in which the extracellular matrix (ECM) components, including type I and III collagen, are excessively deposited in the tissue and difficult to be absorbed or remodelled by the body. The term “abnormalscar” is therefore used to distinguish it from “normalscar”. Although keloid scars have many similar properties to hyperplastic scars and are often described together as HS,K, K is also included in the category of benign tumours because of its tendency to grow in a tumour-like fashion. HS and K are also referred to as “healing skin wounds” because of the damage they cause to the body. He Renliang, Department of Dermatology, Guangdong Dermatology Hospital
From a clinical point of view, pathological scarring is often classified into many types, such as hyperplastic scarring, atrophic scarring, contracture scarring, superficial scarring, depressed scarring, linear scarring, webbed scarring and bridging scarring, according to its different morphology and the different impairments it causes to function. These classifications are not pathological and can only be used as a reference for clinical treatment selection.
II. Mechanism of scar proliferation
Factors involved in causing pathological scar hyperplasia.
1. Analysis of general factors
(1) Ethnicity and skin colour: scar lesions can occur in all populations, with pathological scarring occurring in about 5-15% of all wounds, but the incidence is higher in people of colour, especially black people, and can be 5-15 times higher in blacks than in whites (1), which is related to more pigment cells, pigment hormones are most likely to provoke a response, and abnormalities in melanocyte hormones may be related to scarring.
(2) Genetic factors: In the book on plastic surgery edited by McCARTHY (2) a set of photographs is consistently cited showing a pair of contracted siblings with keloids of similar shape occurring in almost identical multiple areas, and their mother and grandmother both had very similar lesions. In China (3), the results of a family genetic survey of four keloid cases were reported, in which 28.28% (28) of the total number of keloid lesions occurred in four families of 99 members. The reporters concluded that the genetic predisposition was autosomal dominant.
(3) Individual qualities: age: pathological keloid scars are more likely to occur in adolescents, which is associated with the period of puberty, vigorous tissue growth and responsiveness to trauma. About cicatricialdiathesis: Many people and even some medical practitioners often refer to people who are prone to keloid growth as “keloid”. Although some genetic phenomena have been reported, the vast majority of patients are not associated with this condition. Many patients with what are called “keloid” conditions do not have pathological scarring in all areas of trauma. In China, skin samples have been taken from non-lesioned areas of keloid patients compared to corresponding areas of non-keloid patients and analysed for collagen synthesis by fibroblasts and their response to TGF-β. It should be acknowledged that some individuals are more susceptible to pathological scarring, but the term “keloid” should only be used if there is evidence of this.
(4) The effect of injury and level of medical management on the development of pathological scarring: The relationship between skin tension and scarring is well known. Wounds or incisions that are parallel to the relaxedskintensionline (RSTL) are less likely to develop scarring because they are less tense. However, many wounds with tension do not necessarily show significant scarring, whereas wounds without tension may produce significant pathological scarring. This suggests that tension is only one of the factors that may influence scar growth. There is a relationship between the site of the injury and the occurrence of scarring. The lower chin area, deltoid area and anterior sternal area are prone to hyperplastic scarring, whereas the eyelids, forehead, external genitalia and areola area are less prone to pathological scarring. Wound infection, foreign body retention, rough surgical procedures, large stitches, poor wound alignment and tight knots are all contributing factors to hyperplastic scarring. The longer the wound heals, the greater the chance of pathological scarring. According to Deitch(4), the incidence of hyperplastic scarring is 0-6% for those whose wounds heal in 10 days, 4-19% for those whose wounds heal in 10-14 days, 30-35% for those who heal in 14-21 days, and 50-83% for those who heal in more than 21 days. This suggests that early wound healing is an effective measure to reduce scar growth. The environment of the injured area also has a close relationship with the occurrence of scarring. Hypoxia can induce scar proliferation, and increased lactic acid and free radical production in the wounded area are important factors in the development of pathological scarring.
2. Bioactive factors and scar proliferation
After trauma, a series of complex biological reactions occur in the wounded area: cell infiltration, neutrophil aggregation, increased number of macrophages, increased collagen and matrix synthesis by fibroblasts, granulation tissue formation, etc. The diversity and synthesis of cells in the trauma zone is regulated by a number of growth factors. Among these, platelet-derived growth factor (PDGF), transforming growth factor (TGF), epidermal growth factor (EGF), fibroblast growth factor (FGF), and insulin-like growth factor (IGF-1) appear to be more active.
(1) TransformingGrowthFactor-beta (TGF-beta): TGF-beta is most closely associated with scar growth. It has five isoforms, of which TGF-β1, TGF-β2 and TGF-β3 have been identified in mammalian cells and tissues; TGF-β1 was first isolated from platelets and TGF-β2 from osteoblasts. its function. In fact, TGF-β can be synthesised by a variety of cells, such as platelets, macrophages, lymphocytes, fibroblasts and keratinocytes. Cromack measured the level of TGF-β in mouse wound fluid and found that it increased in the early post-wound period and decreased as the wound was closed. The peak level of TGF-β was found on the seventh day after injury. The addition of TGF-β to fibroblast cultures of fetal skin resulted in the expression of type I collagen genes, which were not previously expressed, and caused scarring, and Gallivan, Bullard et al. found that collagenase levels were higher in fetal skin at 6 months of age than in adult skin, while TGF-β levels were lower, which was the basis for early scar-free fetal wound healing. Exogenous TGF-β can cause scarring in early fetal wounds, partly due to its ability to reduce collagenase synthesis and scarring due to low collagen breakdown.
TGF-β has a role in promoting wound healing and is also the main cytokine that stimulates pathological scar growth. Low concentrations of TGF-β1 are potent chemotactic agents for macrophages and neutrophils. Through autocrine and paracrine secretion, the local concentration of TGF-β increases, which in turn activates macrophages to increase the mRNA expression of TGF-β and promote fibroblast proliferation. High concentrations of TGF-β induce the production of other growth factors such as IL-1, FGF, TNF-α, PDGF, and TGF-α. TGF-β1 strongly promotes the synthesis of procollagen I, stimulates the synthesis of fibronectin, provides a network for collagen accumulation, and facilitates the movement of inflammatory cells towards the injured area. inhibits metalloproteinase activity and promotes scarring.
In contrast to TGF-β1,2, which is an effective measure to eliminate pathological scarring, TGF-β3 counteracts the scarring effect of TGF-β1,2, producing an inhibitory effect on scar growth.
(2) FibroblasticGrowthFactor (FGF): FGF has been found to have nine members, of which bFGF (basic fibroblast growth factor), aFGF (acidic fibroblast growth factor) and KGF (keratinocyte growth factor) have been more clearly studied. (i) is a powerful stimulant for cultured cells, promoting DNA synthesis and cell division in endothelial cells and fibroblasts; (ii) promotes capillary neogenesis; (iii) is a chemotactic agent and growth stimulant for fibroblasts. Its combined effect is to promote wound healing and also has some pro-scarring effect.
(3) Platelet-derived growth factor (PDGF) Devil: Platelet-derived growth factor is composed of more than 100 amino acids and there are three forms of PDGF: PDGF-AA, PDGF-BB and PDGF-AB. PDGF is the earliest growth factor to reach the wounded area after trauma and is a strong growth stimulator for mesenchymal cells (e.g. fibroblasts). PDGF-AB promotes wound healing by upregulating gene expression, while PDGF-BB acts by promoting cell division and proliferation.
PDGF+IGF-1 has a better effect on wound healing and has been used clinically to treat decubitus ulcers with good results.
Research on the mechanism of scar contracture
General wound healing is accomplished through a combination of wound contraction, granulation tissue filling and epithelialization. Wound contraction is an important part of wound healing, but excessive contraction can lead to contracture, which can cause serious impairment of shape and function. The strong contraction force of a scar is beyond normal strength and it has been tested that a 1mm diameter collagen fibre can be subjected to a tensile force of 10 to 14kg. The first step in preventing contracture is to find out where the force of contraction is coming from. The conventional view is that myofibroblasts are the driving force behind wound contraction. However, many studies have confirmed that the driving force for wound contraction is primarily fibroblast
(fibroblast). The two different views are still held today.
Myofibroblasts, described by Gabbiani in 1971, are cells with characteristics of fibroblasts and smooth muscle cells, and are found in granulation and scar tissues. The cell morphology is characterised by an elongated cytosol, a polymorphic nucleus with a serrated nuclear membrane and a cytoplasm filled with myofilaments, microfilaments rich in actin, 6-8 nm in diameter, which extend the full length of the cell. The cytoplasm contains a highly expanded rough endoplasmic reticulum, Golgi complexes, free ribosomes and adenosomes. Many microfilaments are in close proximity to extracellular protofibrils, and there are also microfilamentous connections between myofibroblasts (7). Myofibroblasts have both a collagen-secreting function as fibroblasts and a smooth muscle-like contractile capacity. The presence of α-smooth muscle actin (α-SMA) is characteristic of these cells. Myofibroblasts can be labelled with human anti-smooth muscle serum and their contractile effect can be inhibited by topical anti-smooth muscle preparations. During sarcomere formation, a proportion of fibroblasts are converted into myofibroblasts. The shortening of the numerous myofibroblast cytoskeleton drives the surrounding matrix through the action of fibronectin (FN), for example, leading to contraction of the trabeculae. This is the traditional description of myofibroblasts as the driving force of contraction.
Other studies have suggested that fibroblasts, rather than myofibroblasts, are the driving force behind wound contraction. tredgetMusicalNote suggests that alpha-SMA, which represents the characteristics of myofibroblasts, does not appear early in the wound healing process, but appears between 12d and 15 days after injury, when the most active wound contraction activity is largely over. darby found that wounds were Darby found that the wound contracted linearly and rapidly for 12 days after wounding, especially from day 4 onwards, and that the contraction largely ceased after day 12. Immunofluorescence microscopy showed that α-SMA was not expressed in greater numbers until 12-15 days after wounding, with more fibroblasts appearing as microfilaments. It was also confirmed that fibroblasts were the main actors during the peak of wound contraction. Fibroblasts in the stroma cause wound contraction by pseudopod-like stretching, crawling, and producing sustained spindle-like movements.
The validity of both views needs to be determined by more in-depth studies.
IV. Establishment of animal models of proliferative scarring
As proliferative scarring and keloid scarring are difficult to occur or not to occur in animals, there is no real animal model of proliferative scarring produced by animals themselves. Previous research on scarring has been conducted in three main ways: firstly, through tissue cell culture techniques such as fibroblasts; secondly, by transplanting human hyperplastic keloid or keloid tissue under the skin of thymus-free rats (nude mice) for observation; and thirdly, through clinical practice to gain experience. Although the above methods have led to significant progress in scar research, the absence of a true animal model has become a major obstacle to the in-depth study of scarring. For this reason, scholars at home and abroad have been relentlessly exploring for the establishment of animal models of scarring. Following the failure of various animal models for scar production, Shetlar et al. created an experimental model by transplanting human scar tissue into the subcutis of nude mice, providing a new approach to scar research. However, human keloid scars are parasitic in heterozygous animals and in the absence of cellular immunity, and it is not possible to study the onset, development and regression of keloid scars. morris(9) et al. observed excessive dermal proliferation in rabbit ear wounds. We have been creating 6-mm-diameter garden-shaped traumas with full skin defects on the ventral side of the ear of the large-eared white rabbit since 1998 and found that they could produce hyperplastic masses similar to human proliferative keloid scars, with dermal hyperplasia three to four times the thickness of the normal dermis, and light microscopy of massive fibroblast proliferation with a horizontal arrangement in the deeper layers and a circular or swirling structure in the superficial layers, similar to the structure of human proliferative keloids. The former inhibited scar proliferation by injecting IFN-γ or TGF-β1 into the trabecular base, while the latter had a significant injection of pro-keloid proliferation, the response of which was consistent with that of human scarring. The rate of keloid hyperplasia occurring on the ventral surface of rabbit ears is at least 50%, and its duration can be up to about 60 days from the epithelialization of the trabeculae, with the longest maintaining the hyperplastic mass unchanged for over 100 days. (10) On this basis, we also made a large trauma of 1.5cm X 4.5cm rectangular full skin defect on the ventral surface of the rabbit’s ear and found that the incidence of hyperplasia was even higher, with more than 80% of hyperplasia evident and the duration of hyperplasia exceeding 190 d. Tissue sections of hyperplasia at different stages were subjected to in situ hybridization, and mRNA of type I and III pre-collagen and TGF-β were detected by cDNA probes, The results showed that all three were highly expressed in the early growth masses, and the mRNA expression of all three tended to decrease with time. The observation of nearly 300 wounds on the ventral surface of 56 rabbits confirmed that similar pathological changes to human proliferative scars could occur, especially in large rectangular wounds with high incidence and long duration, which could be an animal model for proliferative scarring. This could be a new approach to the study of scarring!
V. Clinical and pathological commonalities and differences between proliferative keloid scars and keloid scars
(i) Hyperplastic keloid scars and keloid scars belong to the same group of dermal fibrotic diseases.
The essence of both HS,K is that fibroblast-based cells proliferate and increase in activity, producing large amounts of collagen and causing large deposits of extracellular mesenchymal (ECM) components, including type I and III collagen, in the tissue, which are difficult to be absorbed or remodelled by the body.
1. The role of cellular components in the process of scar proliferation
(1) Fibroblast: Fibroblasts originate from mesodermal mesenchymal cells during the embryonic period, with large cytosomes and large nuclei, lightly coloured chromatin, obvious nucleoli, and abundant rough endoplasmic reticulum, free ribosomes and well-developed Golgi complexes in the cytoplasm. These structures suggest that fibroblasts are in an active state of collagen production and secretion. Fibroblasts are the main cells that produce scarring. After the onset of trauma, fibroblasts in the injured area proliferate and nuclear division increases significantly. From 5-6 days after the injury, the fibroblasts begin to synthesise and secrete collagen and other matrixes in increasing amounts, becoming a component of granulation tissue that fills the wound. The function of fibroblasts is regulated by a variety of growth factors. PDGF and FGF drive them from the G0 and G1 phases of the cell cycle into the division phase; EGF, TGF-α and IGF-1 promote the transition of sensory cells to the S phase of the cell cycle and promote cell division. Among them, TGF-β1,2 has a stronger role in promoting extracellular matrix secretion.
(2) Mast cells: Mast cells are derived from bone marrow and are cells with a small, garden-like nucleus. They play an important role in all stages of wound healing, especially in the process of granulation tissue production and development and maturation. Mast cells increase in the injured area 3-5 days after the injury, and their number reaches a peak on the 8th day. According to statistics, the number of mast cells in normal skin is 25 cells/mm2, while in HS it can reach 304 cells/mm2 (11), and 65% are of the naive type. It is mainly found around the blood vessels of the dermal papillae. The cytoplasm is filled with coarse basophilic granules that synthesize heparin, 5-hydroxytryptamine, histamine, leukotrienes, protein hydrolases and bioactive substances – TNF-α, IFN-γ, IL-1,3,4,5,6, GM-CSF (granulocyte-macrophage colony stimulating factor), etc. By storing and releasing these active substances, especially histamine, mast cells are a powerful stimulus for microvascular endothelial cells, causing massive microvascular proliferation and promoting fibroblast proliferation, leading to scarring.
(3) Macrophage: Macrophages, also known as histiocytes, are cells that differentiate from monocytes in the blood after they have penetrated the walls of blood vessels. Macrophages account for 80% of the cells that migrate to the injured area 7 days after injury, and are the main phagocytes in the inflammatory phase. They can both remove cells from the injured area and release some bioactive substances such as TGF, IL, TNF, PDGF, etc. Macrophages are abundant in sparse connective tissue. During scar formation, Macrophage-derived GrowthFactor (MDGF) induces the conversion of resting fibrocytes into fibroblasts and promotes capillary neogenesis. On the other hand, macrophages secrete IFN, IL-6, prostaglandin E2 and other factors that inhibit fibroblasts. During the transformation of granulation tissue to normal connective tissue, it is involved in tissue remodelling activities by regulating the synthesis and degradation of the extracellular matrix, causing repeated lysis, deposition and renewal of collagen.
In addition, lymphocytes are also involved in the process of scar proliferation.
2. The role of matrix components in scar formation
Matrix is a homogeneous substance with no fixed morphological structure, mainly consisting of biological macromolecules. The extracellular matrix (ECM) is composed of collagen (collagen types I-XIX), structural proteins (laminin, LN; fibronectin, FN) and proteoglycan (PG), etc. The ECM not only acts as a tissue scaffold, but also has many important It also has a number of important physiological functions.
(1) Collagen and scar growth: Collagen, also known as collagenous, is a protein formed by three alpha peptide chains that are spirally entwined. Collagen molecules are typed according to the combination of unique polypeptide chains that form different types or heterotrimers, e.g. α1(I) indicates the α1 chain of type I collagen. Nineteen types of collagen molecules have been defined to date (12). Type I collagen is the most widely distributed, accounting for 80-85% of total collagen in the skin and acting as a scaffold in the tissues. Type II collagen is only found in cartilage and the vitreous humor of the eye and has a role in promoting chondrocyte differentiation. Type III collagen accounts for 15-20% of the collagen in the skin and is also found in tendons, blood vessels, fascia and cartilage. Type III collagen is more abundant in the more elastic tissues and those with more type III collagen have finer fibrous bundles. Type IV collagen, known as basement membrane collagen, is found in various basement membranes and its function is related to cell regeneration and tumour growth. Type V collagen is mainly found at the cell-matrix interface, in lung tissue and in the blood vessels of various substantive organs. It has an anticoagulant effect and is involved in the fibrotic process in some pathological tissues. An increase in type V collagen has been found in lung scar carcinoma tissue. Type VI collagen is an endothelial collagen, the function of which is still unclear. In vitro cultures of fibroblasts were found to have a 3:1 ratio of type I to type VI collagen, suggesting that type VI collagen is a more abundant source than type III collagen. Type VII collagen is found in the superficial layers of the skin and is associated with the dense layer of the basement membrane, playing a role in fixing the epidermis.
In the skin it is mainly type I and III collagen, the ratio of which varies with age: the ratio of type I to type III collagen content is 0.8/1 in fetal skin at 15 weeks, 3.6/1 in those 3 months after birth and 3.5-6/1 in adults. type III collagen content increases in the early stages of wound healing and gradually returns to normal over time. The ratio of type I to type III collagen in hyperplastic scars is 2:1, with type III collagen content exceeding 30%, whereas its ratio in keloids is 19:1, with type III collagen content considerably lower than in HS and also lower than in normal skin (13).
(2) Collagen synthesis:The molecular unit of collagen is protocollagen, which is made up of three polypeptide alpha chains containing 1000 amino acids each, 33% of which are glycine and 20% are sialic acids – such as proline and hydroxyproline. In the nucleus, the collagen gene is activated and transcribed into mRNA, which then enters the cytoplasm and forms three alpha peptide chains on the ribosomes of the rough endoplasmic reticulum, which are catalysed by hydroxyprolinase and hydroxylysinase to form hydroxyproline and hydroxylysine, which are important components of collagen fibres. Procollagen, consisting of three alpha peptide chains, is excreted outside the cell by the Golgi complex through microtubules and is then specifically excised by peptidases from the amino and hydroxyl ends of the peptide chains to become procollagen. The collagen molecules polymerise to form microfibrills, many of which form fibrils, which can be seen under the electron microscope as a 64 nm periodic transverse pattern of light and dark. The fibrils are bonded to each other by a glycoproteiniccement, thus forming collagen fibres.
Collagen fibres are highly resilient, with a 1mm diameter collagen fibre being able to withstand a tensile force of 10-14kg, which explains the strong contractile force produced during scar contracture.
Hydroxyproline is an amino acid unique to collagen, accounting for 10% of the amino acids in collagen (14). It is present in the blood in three forms: free, protein-bound and peptide-bound, of which the free and peptide-bound forms are metabolites of hydroxyproline and are excreted in the urine. The amount excreted in normal 24-hour urine is about 33mg, and the normal blood level of hydroxyproline is about 12μmol/L. Measuring these values can reflect the level of collagen synthesis and metabolism, and indirectly the state of scar formation.
(3) Relationship between structural proteins and scar formation: Structural proteins refer to basement membrane ligand proteins or laminin (LN) and fibronectin (FN), a group of macromolecular glycoproteins reported by Morrison (1948) and others, with molecular weights of 440,000~450,000. FN can be produced from the rough endoplasmic reticulum, intracytoplasmic vesicles and Golgi complex of fibroblasts. Its functions include maintaining cell-matrix and cell-cell adhesion. FN can stimulate monocytes to release FGF, which can also attract fibroblasts and endothelial cells to the injured area, and these fibroblasts can rapidly synthesize and secrete large amounts of FN and type III collagen. These fibroblasts in turn synthesize and secrete large amounts of FN and type III collagen. When the wound is epithelialised and the collagen matures, the FN content decreases or even disappears. Fibronectin is therefore considered to be a precursor and stage marker of the fibrosis process.
The highest FN content in the mid-dermis of the scar was demonstrated by immunohistochemistry, indicating that the proliferative activity of the scar mainly occurred in the mid-dermis, while the FN in the sub-dermis was distributed in a dendritic pattern deep into the subcutis, inducing fibroblasts to migrate and proliferate to the subcutis, causing the scar to develop deeper.
(4) The role of proteoglycans in scar growth: Proteoglycans are composed of core proteins and glycosaminoglycans (GAG), including chondroitin sulphate, heparin and hyaluronic acid. Of these, hyaluronic acid is more closely associated with the formation of scarring. Hyaluronic acid (HA) acts as a gliding agent in the group, providing a stretchy environment, inhibiting fibroblast differentiation, reducing collagen production and deposition, increasing the proportion of type III collagen, and promoting regular collagen arrangement, thus inhibiting scar growth. In a study conducted by SMC, the proliferation of fibroblasts and collagen synthesis were inhibited when HA was added to the three-dimensional culture of fibroblasts at a concentration of 1μg/ml; the inhibitory effect was most pronounced when the concentration reached 10~100μg/ml. A concentration of 0.1μg/ml of hyaluronic acid stimulating factor (HASF) promoted HA production by fibroblasts, and the amount of HA production increased as the concentration of HASF increased and the duration of action increased, showing a time- and dose-dependent effect. Studies of non-scarring healing of early fetal wounds confirm that high levels of HA and HASF in the early fetal wound area are one important factor, and low levels of TGF-β are another important factor.
Hyaluronic acid has been used clinically for the prevention and treatment of scarring. HASF has been used on deep II0 burn wounds, resulting in earlier healing and a flatter appearance of the healed wounds with finer collagen fibres and higher type III collagen content, indicating that HS has an anti-keloidal effect.
(ii) Difference between proliferative keloid and keloid
The clinical term for hypertrophic lesions that are confined to the injury area is hypertrophic scarring.
The distinction between hypertrophic scars (HS) and keloid scars (K) is clearly not strictly defined. In fibroblasts from HS and K, the mRNA ratios of type I and III pre-collagen differed, with normal fibroblasts having a ratio of 6:1 compared to 22:1 in K. The mRNA of type I pre-collagen was selectively transcriptionally enhanced, whereas the ratio of type III pre-collagen was significantly lower. The type III collagen ratio is high in HS compared to K and is higher than in normal skin. Of course, it is not easy to essentially delineate HS from K.
Photomicroscopically: covered by atrophic epithelium, with a thick keratinised layer and loss of dermal papillae, there is a large amount of connective tissue and dilated capillaries, inflammatory cells and myofibroblasts. By 6 to 24 months, congestion is reduced, capillaries are reduced and collagen is numerous and irregular, arranged in a swirling pattern. There are deposits of mucopolysaccharide proteins between collagen fibres.
On electron microscopy, there are fibroblasts of different ages, with oval nuclei and often cut marks, an abundant and dilated endoplasmic reticulum, well-developed Golgi apparatus and secretory vesicles, lysosome-like structures in a few fibroblasts, more macrophages, and unevenly spaced collagen fibres with a diameter of about 40-80 nm. Under scanning electron microscopy, the collagen fibres appear as swirling or nodular structures, and skin attachments are rare.
On light microscopy, the epidermis may be atrophic and the dermal papillae reduced, or the epidermis may be normal and the dermal papillae visible, with skin attachments present. There is a large number of fibroblasts in the early stages, as well as focal aggregations of mast cells, plasma cells and a few lymphocytes. The cells show a schizophrenic phase with vitreous degeneration and some have lost their nuclei.
Electron microscopy: compared with HS, the keloid has more myofibroblasts with oval, serrated nuclei, abundant euchromatin, distinct nucleoli, abundant rough endoplasmic reticulum in the cytoplasm, well-developed mitochondria and Golgi apparatus, and especially myofilaments filled with slender myofilaments arranged parallel to the long axis of the cell and shaped spindle-shaped electron-dense areas (dense bodies). Scanning electron microscopy: smooth surface, keratinised and desquamated, no dermatoglyphic pattern, poorly demarcated cells. The dermal reticular layer also has a swirling structure, but it is not as well defined as in hyperplastic scarring, and contains loose, coarse pro-collagen fibres and a few small, curved elastin fibres. In the infiltrative type, the epidermis is atrophic and the dermal reticular layer has tight collagen with small gaps and, in some cases, a nodular structure.
Although some differences between hyperplastic keloids and keloid scars can be identified in the above data, there is insufficient information to essentially distinguish hyperplastic keloids from keloid scars. Some studies have also found that the two do not respond to certain growth factors in the same way. More in-depth studies are needed to strictly differentiate between HS and K.
VI. Prevention and treatment of keloids and keloid scars
(i) Non-surgical treatment
1. Drug treatment
There are many drugs used to prevent and treat hyperplastic keloids and keloid scars. The main ones that are commonly used in clinical practice or have been studied to some extent are: corticosteroids, peptide growth factors, anti-free radical agents, calcium channel blockers, retinoids, enzymes, antihistamines and Chinese herbal preparations.
(1) Corticosteroids: Triamcinolone Acetonide, also known as Triamcinolone Acetonide Injection, is a corticosteroid commonly used for injection into lesions. After injection into the hyperplastic scar tissue or keloid, on the one hand, it inhibits collagen synthesis and GAG production by down-regulating the mRNA of fibroblasts and reduces the excessive accumulation of ECM; on the other hand, it reduces the amount of collagenase inhibitor-α macroglobulin and increases the activity of collagenase,