Collagen Wound Healing Research Articles

Biomedical applications of collagen: A Review

Collagen is an excellent biomaterial. Biological characteristics of collagen including biodegradability and weak antigenicity made it a primary resource in medical application. In biomedical field collagen is mainly used as sponges for wound/burn, supplement in rheumatoid arthritis, drug delivery system, controlling material for transdermal delivery and basic matrices for cell culture system due to its ability to stimulate formation of tissue and organ. Moreover, collagen is also applied in tissue engineering including bone defect, tissue regeneration, skin replacement and artificial blood vessels and valves. The article reviews biomedical application of collagen in wound healing, rheumatoid arthritis, drug delivery system, tissue engineering and lung function improvement in pulmonary fibrosis due to viral infection.

Review: fish collagen: extraction, characterization and application in wound healing and drug delivery

Collagen is a natural protein presenting in the animal and human’s body. It is in natural fibrous and could be found in the connective tissue and flesh of mammal, approximately 25-35 wt.% of total human protein. Collagen is abundant in fibrous tissues such as: bones, cartilage, tendons, blood vessels, ligaments, skin, cornea, aortic disc and intestines. Fish collagen is currently being studied as a new biological substitute for collagen from animals. It extracted from by-products (scales, skins, bones, etc.) by biochemical or biological methods is safe, has high adsorption, high compatible. The factors influencing on the extraction process include temperature, time, concentration of ingredients, etc. The fish collagen is usually collagen type I with a fibril structure. Each unit of collagen is tropocollagen consisting of three polypeptide chains twisted together. Depending on the source of ingredients, the composition of aminoacids, denaturation temperature, the sequence of aminoacids, structure, morphology, molecular weight, extraction yield, etc. of obtained collagens are different. This paper reviews the extraction and characterization of fish collagen from products after fish processing by chemical or biochemical methods. The applications of fish collagen in wound healing and drug delivery are also reviewed.

Role of Collagen in Wound Healing of Fishes

Role of Collagen in Wound Healing of Fishes

Collagen in Wound Healing.

Normal wound healing progresses through inflammatory, proliferative and remodeling phases in response to tissue injury. Collagen, a key component of the extracellular matrix, plays critical roles in the regulation of the phases of wound healing either in its native, fibrillar conformation or as soluble components in the wound milieu. Impairments in any of these phases stall the wound in a chronic, non-healing state that typically requires some form of intervention to guide the process back to completion. Key factors in the hostile environment of a chronic wound are persistent inflammation, increased destruction of ECM components caused by elevated metalloproteinases and other enzymes and improper activation of soluble mediators of the wound healing process. Collagen, being central in the regulation of several of these processes, has been utilized as an adjunct wound therapy to promote healing. In this work the significance of collagen in different biological processes relevant to wound healing are reviewed and a summary of the current literature on the use of collagen-based products in wound care is provided.

Anti-miR-200b promotes wound healing by regulating fibroblast functions in a novel mouse model.

MicroRNA-200b (miR-200b) down-regulation has been found in wound-healing tissues. Fibroblasts are the predominant cells that orchestrate the production of collagen in wound healing. However, it is still unclear whether miR-200b can affect the wound healing by regulating the fibroblasts' function. The current rodent wound-healing models are not ideal due to their marked difference in structure compared with the human skin. In this study, we demonstrated that the murine plantar skin had similar anatomical features to the human skin. Using this model, the gain/loss-of-function studies showed that miR-200b caused a significantly delayed wound healing in vivo. Furthermore, using cell proliferation, migration and collagen synthesis assays, we found that miR-200b attenuated cell proliferation, migration and collagen synthesis of fibroblasts, which are critical aspects of wound healing. miR-200b also decreased the expression of Zeb1. Collectively, we established a new murine plantar skin model for the investigation of wound healing, and based on it we found that miR-200b affected the wound healing by regulating the biological function of fibroblasts, which provided a new insight for wound healing.

The significance of collagen dressings in wound management: a review.

Clinical experience and research has improved our understanding of wound healing which, in turn, has enabled health professionals to aid wound healing and manufacturers to develop modern wound dressings. The significant role of collagen in wound healing has led to the development of numerous products on the basis of this biological material. The main focus of this review is to provide a critical appraisal of publications about collagen and acellular collagen dressings with a fleece-like or spongy structure. It is intended for clinicians and researchers, and aims to keep them up-to-date in the complex field of interactive, collagen-based wound dressings, including their manufacture, combination possibilities, mechanisms of action, performance in the promotion of wound healing and indications. Despite the small number of clinical studies, the importance of acellular collagen dressings with a fleece- or sponge-like structure is likely to increase in the future. As there is no ideal wound dressing, the knowledge attained is meant to support health professionals in selecting the right product, and pave the way for new applications and clinical studies.

UV fluorescence excitation imaging of healing of wounds in skin: Evaluation of wound closure in organ culture model.

Background and ObjectiveMolecules native to tissue that fluoresce upon light excitation can serve as reporters of cellular activity and protein structure. In skin, the fluorescence ascribed to tryptophan is a marker of cellular proliferation, whereas the fluorescence ascribed to cross‐links of collagen is a structural marker. In this work, we introduce and demonstrate a simple but robust optical method to image the functional process of epithelialization and the exposed dermal collagen in wound healing of human skin in an organ culture model.Materials and MethodsNon‐closing non‐grafted, partial closing non‐grafted, and grafted wounds were created in ex vivo human skin and kept in culture. A wide‐field UV fluorescence excitation imaging system was used to visualize epithelialization of the exposed dermis and quantitate wound area, closure, and gap. Histology (H&E staining) was also used to evaluate epithelialization.ResultsThe endogenous fluorescence excitation of cross‐links of collagen at 335 nm clearly shows the dermis missing epithelium, while the endogenous fluorescence excitation of tryptophan at 295 nm shows keratinocytes in higher proliferating state. The size of the non‐closing wound was 11.4 ± 1.8 mm and remained constant during the observation period, while the partial‐close wound reached 65.5 ± 4.9% closure by day 16. Evaluations of wound gaps using fluorescence excitation images and histology images are in agreement.ConclusionsWe have established a fluorescence imaging method for studying epithelialization processes, evaluating keratinocyte proliferation, and quantitating closure during wound healing of skin in an organ culture model: the dermal fluorescence of pepsin‐digestible collagen cross‐links can be used to quantitate wound size, closure extents, and gaps; and, the epidermal fluorescence ascribed to tryptophan can be used to monitor and quantitate functional states of epithelialization. UV fluorescence excitation imaging has the potential to become a valuable tool for research, diagnostic and educational purposes on evaluating the healing of wounds. Lasers Surg. Med. 48:678–685, 2016. © 2016 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Does L to D-amino acid substitution trigger helix→sheet conformations in collagen like peptides adsorbed to surfaces?

The present work reports on the structural order, self assembling behaviour and the role in adsorption to hydrophilic or hydrophobic solid surfaces of modified sequence from the triple helical peptide model of the collagenase cleavage site in type I collagen (Uniprot accession number P02452 residues from 935 to 970) using (D)Ala and (D)Ile substitutions as given in the models below: Model-1: GSOGADGPAGAOGTOGPQGIAGQRGVV GLOGQRGER. Model-2: GSOGADGP(D)AGAOGTOGPQGIAGQRGVVGLOGQRGER. Model-3: GSOGADGPAGAOGTOGPQG(D)IAGQRGVVGLOGQRGER. Collagenase is an important enzyme that plays an important role in degrading collagen in wound healing, cancer metastasis and even in embryonic development. However, the mechanism by which this degradation occurs is not completely understood. Our results show that adsorption of the peptides to the solid surfaces, specifically hydrophobic triggers a helix to beta transition with order increasing in peptide models 2 and 3. This restricts the collagenolytic behaviour of collagenase and may find application in design of peptides and peptidomimetics for enzyme-substrate interaction, specifically with reference to collagen and other extra cellular matrix proteins.

Engineering D-Amino Acid Containing Collagen Like Peptide at the Cleavage Site of Clostridium histolyticum Collagenase for Its Inhibition.

Collagenase is an important enzyme which plays an important role in degradation of collagen in wound healing, cancer metastasis and even in embryonic development. However, the mechanism of this degradation has not yet been completely understood. In the field of biomedical and protein engineering, the design and development of new peptide based materials is of main concern. In the present work an attempt has been made to study the effect of DAla in collagen like peptide (imino-poor region of type I collagen) on the structure and stability of peptide against enzyme hydrolysis. Effect of replacement of DAla in the collagen like peptide has been studied using circular dichroic spectroscopy (CD). Our findings suggest that, DAla substitution leads to conformational changes in the secondary structure and favours the formation of polyproline II conformation than its L-counterpart in the imino-poor region of collagen like peptides. Change in the chirality of alanine at the cleavage site of collagenase in the imino-poor region inhibits collagenolytic activity. This may find application in design of peptides and peptidomimics for enzyme-substrate interaction, specifically with reference to collagen and other extra cellular matrix proteins.

Lucky VII? A Dual Role for Collagen in Wound Healing

The extracellular matrix protein collagen VII creates a microenvironment ripe for proper wound healing.

Effect of Gentamicin-absorbed Collagen in Wound Healing in Pilonidal Sinus Surgery: A Prospective Randomized Study

Pilonidal sinus is a common disease that causes the loss of many working hours, but treatment is variable and problematic. The effect of gentamicin-absorbed collagen on healing, infection and recurrence, and length of hospital stay were examined after pilonidal sinus surgery. Patients undergoing surgical treatment for pilonidal sinus were randomly assigned into two groups each of 40 patients. Both groups were treated with excision and primary closure under local anaesthesia. Group 1 (control) received oral antibiotics for 7 days post-operatively. In group 2, prior to wound closure, gentamicin-absorbed collagen sponges were placed on the sacral fascia and these patients did not receive oral post-operative antibiotic therapy. Patients in group 2 had a significantly shorter mean wound healing time, significantly lower infection and recurrence rates, and a significantly shorter hospital stay than those in group 1. It is concluded that implantation of a gentamicin-containing collagen sponge on the wound area in pilonidal sinus decreased the rates of infection and recurrence, and shortened the hospital stay.

Collagen in Wound Healing: Are We Onto Something New or Just Repeating the Past?

Collagen in Wound Healing: Are We Onto Something New or Just Repeating the Past?

Trace elements content in serum, normal skin, and scar tissues of keloid and normal scar patients

AbstractWound healing is a normal physiological process that occurs after injury. Scars are usually formed, and the nature of the scar depends on the balance between the formed and degraded collagen during healing. A balanced production and degradation of collagen in wound healing results in the formation of a normal scar whereas an imbalance produces what is known as keloid scar. The factors that cause an imbalance are not well identified, although many factors, such as immunity, genetic, ischaemia, hormonal, growth, and nutritional factors, are blamed. This study was undertaken to investigate trace elements level in the serum, normal skin, and scar tissue of patients with normal and keloid scars. Copper (Cu), zinc (Zn), selenium (Se), and manganese (Mn) levels were estimated in 100 (50 with normal scars and the others with keloids) patients. The serum level of Zn was found to be higher in keloid scar patients, and this increase was highly significant (P < 0.0001). The level of Cu was significantly higher (P < 0.0001) in the normal skin and scar tissues of keloid patients. Trace element levels in scar tissues were observed to be lower in comparison to normal skin trace element content in both groups. The significant changes of Zn in serum and Cu in skin and scar tissues of keloid patients as noted in this study may suggest their role in the regulation of behavior of scar formation in wound healing. J. Trace Elem. Exp. Med. 15:57–66, 2002. © 2002 Wiley‐Liss, Inc.

Retinoic acid enhances the effect of collagen on bone union, following induced non-union defect in guinea pig ulna.

The aim of the present study is to evaluate the involvement of retinoic acid and collagen in wound healing, by combining them in a therapeutic modality for treating a non-union bone defect in a guinea-pig ulnar-bone model. a 4-mm disc was excised from the guinea-pig's ulnar-bone, and the space formed between the two ulnar fragments was filled with either collagen solution, retinoic acid solution or a combination of both. The guinea-pigs were sacrificed 2 or 6 weeks later, and the defected ulnar bones were studied by X-ray, by histology and by computerized histomorphometry. After 6 weeks, the long bone area fraction within the histological sections of the bone, was increased after treatment with this mixture by 180%, as compared to the untreated controls. The cartilage area in those sections was decreased by 44% after the combined treatment, as compared to increases of 133% and 182% following treatments with collagen alone. These findings demonstrate that addition of 500 IU of retinoic acid to collagen at a site of a bone defect, is superior to either agent in enhancing regeneration of new bone, achieving union across the defect and leading to its complete repair.

Epidermal growth factor modifies the expression and function of extracellular matrix adhesion receptors expressed by peritoneal mesothelial cells from patients on CAPD.

Efficient peritoneal dialysis depends on an intact layer of mesothelial cells that line the peritoneal membrane. This layer is disrupted in patents on continuous ambulatory peritoneal dialysis during episodes of peritonitis (acute injury) and replaced by fibrous tissue during extended dialysis (chronic injury). Little is understood of human peritoneal mesothelial cell (HPMC) responses to wounding and episodes of peritonitis. HPMC were harvested from spent peritoneal dialysis effluent and maintained under defined in vitro conditions. Adhesive interactions with extracellular matrix (ECM) molecules and chemotactic and wound-healing responses were measured in vitro using purified ECM molecules. HPMC express multiple functional cell receptors recognizing and binding to ECM molecules, including several members of the integrin family. HPMC exhibit directed migration in wound healing and chemotaxis assays with ECM molecules. Epidermal growth factor (EGF) stimulates a reversible change to a fibroblastic phenotype, accompanied by increased expression of beta1 integrins, particularly alpha2beta1, increased adhesion to type I collagen, and significantly greater HPMC migration on type I collagen in wound healing and chemotaxis assays. HPMC possess the migratory capacity to contribute to the efficient repair of damaged peritoneal membrane after acute injury, and growth factors, such as EGF, facilitate peritoneal membrane healing by augmenting cell adhesion and migration.

Production of Collagen Type I by Mouse Peritoneal Macrophages

The origin and identity of the cells that accumulate and produce collagen in wound healing and in granulomatous and fibrotic processes have long remained unsettled. In this study, it was found that pure cultures of peritoneal macrophages produced hydroxy-L-proline not associated with Clq and produced detectable quantities of collagenase-digestible protein. Cultured macrophages synthesized collagen while retaining their phagocytic capacity. Immuno-blot analysis identified the collagen as Type I. This shows that macrophages have collagen-forming capacity and may be productive cells in pathologic collagen deposition.

Differential staining of collagen types in paraffin sections: a color change in degraded forms.

The Herovici combination of picro methyl blue or aniline blue and picro acid fuchsin in proper proportion colors mature dense collagen red while reticulum and newly formed collagen are blue. Fetal collagen, wound healing collagen, subepidermal finely fibrillar collagen, deteriorating collagen in and over arterio-sclerotic lesions tend to take the blue stain. Arterial adventitial, deep dermal gastric submucosal collagens are red.

Collagen in wound healing : Laufer M., Ashkenazi C., Katz D. and Wolman M. (1974) Orientation of collagen in wound healing. Br. J. Exp. Pathol.55, 233

Collagen in wound healing : Laufer M., Ashkenazi C., Katz D. and Wolman M. (1974) Orientation of collagen in wound healing. Br. J. Exp. Pathol.55, 233

Collagen in wound healing

Collagen in wound healing