fibrin and Cicatrix

Fibrin is a topical haemostat, sealant and tissue glue, which consists of concentrated fibrinogen and thrombin. It has broad medical and research uses. Recently, several studies have shown that engineered patches comprising mixtures of biological or synthetic materials and progenitor cells showed therapeutic promise for regenerating damaged tissues. In that context, fibrin maintains cell adherence at the site of injury, where cells are required for tissue repair, and offers a nurturing environment that protects implanted cells without interfering with their expected benefit. Here we review the past, present and future uses of fibrin, with a focus on its use as a scaffold material for cardiac repair. Fibrin patches filled with regenerative cells can be placed over the scarring myocardium; this methodology avoids many of the drawbacks of conventional cell-infusion systems. Advantages of using fibrin also include extraction from the patient's blood, an easy readjustment and implantation procedure, increase in viability and early proliferation of delivered cells, and benefits even with the patch alone. In line with this, we discuss the numerous preclinical studies that have used fibrin-cell patches, the practical issues inherent in their generation, and the necessary process of scaling-up from animal models to patients. In the light of the data presented, fibrin stands out as a valuable biomaterial for delivering cells to damaged tissue and for promoting beneficial effects. However, before the fibrin scaffold can be translated from bench to bedside, many issues must be explored further, including suboptimal survival and limited migration of the implanted cells to underlying ischaemic myocardium. Copyright © 2016 John Wiley & Sons, Ltd.

Topics: Animals; Cell Transplantation; Cicatrix; Fibrin; Humans; Myocardial Infarction; Tissue Scaffolds

What is the relationship between the wound-healing process and the development of cancer? Malignant tumours often develop at sites of chronic injury, and tissue injury has an important role in the pathogenesis of malignant disease, with chronic inflammation being the most important risk factor. The development and functional characterization of genetically modified mice that lack or overexpress genes that are involved in repair, combined with gene-expression analysis in wounds and tumours, have highlighted remarkable similarities between wound repair and cancer. However, a few crucial differences were also observed, which could account for the altered metabolism, impaired differentiation capacity and invasive growth of malignant tumours.

Topics: Animals; Cicatrix; Epithelium; Extracellular Matrix; Fibrin; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Inflammation; Models, Biological; Neoplasms; Neovascularization, Physiologic; Wound Healing

The healing of an adult skin lesion is a well studied but complex affair of some considerable clinical interest. Endogenous growth factors, including the EGF, FGF, PDGF and TGF beta families, are released at the wound site and presumed to be a necessary part of the natural wound healing machinery. Moreover, members of each of these families have been shown to enhance healing if added exogenously to a wound site. In this review we shall briefly discuss what is known about the mechanics and cell biology of adult wound healing, describe the normal cellular source of growth factors during the healing process and, with reference to their known capacities in tissue culture, speculate as to how particular growth factors might be able to enhance healing.

Topics: Animals; Cells, Cultured; Cicatrix; Connective Tissue; Epidermal Growth Factor; Fibrin; Fibroblast Growth Factors; Gene Expression Regulation; Growth Substances; Humans; Inflammation; Keratinocytes; Male; Mice; Platelet-Derived Growth Factor; Receptors, Cell Surface; Salivary Proteins and Peptides; Skin; Transforming Growth Factors; Wound Healing

Topics: Adrenal Cortex Hormones; Adrenal Glands; Adult; Afibrinogenemia; Age Factors; Aged; Anticoagulants; Antineoplastic Agents; Blood Proteins; Child; Cicatrix; Fibrin; Growth Hormone; Hemophilia A; Humans; Insulin; Mineralocorticoids; Pancreas; Postoperative Complications; Vitamins; Wound Healing

Topics: Age Factors; Animals; Avitaminosis; Biomechanical Phenomena; Cats; Cicatrix; Collagen; Connective Tissue; Dehydration; Fibrin; Granulation Tissue; Hormones; Humans; Liver Diseases; Oxygen; Protein Deficiency; Radiation Effects; Rats; Tissue Extracts; Wound Healing; Wounds and Injuries

Topics: Anemia; Animals; Ascorbic Acid; Biomechanical Phenomena; Cicatrix; Collagen; Denervation; Fibrin; Fibroblasts; Glucocorticoids; Glycoproteins; Glycosaminoglycans; Granulation Tissue; Guinea Pigs; Histamine; Humans; Lathyrism; Microbial Collagenase; Oxygen; Rabbits; Rats; Species Specificity; Stress, Physiological; Time Factors; Wound Healing; Wounds and Injuries

To determine the effectiveness of HP802-247 compared with bacitracin ointment in healing wounds resulting from Mohs micrographic surgery.. Open-label, randomized pilot study conducted at a single center. Subjects were randomized to either HP802-247 (5M cells/mL) applied weekly or bacitracin ointment applied daily. Treatment continued for up to 12 weeks or complete wound closure. Primary efficacy was effectiveness as measured by the Investigator's Global Assessment of Healing (IGAH) scale. Secondary outcomes included median time to healing, investigator- and subject-scored signs and symptoms, and an assessment of scar by the investigator at 16 weeks postsurgery.. All subjects achieved favorable outcomes within the study period; however, these were reached more quickly for the HP802-247 group than for bacitracin. At 3 weeks postsurgery, healing was assessed as very effective for 75% of subjects in the HP802-247 group compared with 50% for bacitracin. Median time to closure was 24.5 days for HP802-247 and 29 days for bacitracin. Scores for signs and symptoms and scar were similar for both groups but, in general, were numerically better for HP802-247.. In this small pilot study, HP802-247 was found to provide a modest, incremental benefit in the healing of Mohs micrographic surgery wounds, suggesting that the healing of uncomplicated acute wounds may be slightly accelerated without enhancement of scarring.

Topics: Aged; Aged, 80 and over; Bacitracin; Cicatrix; Female; Fibrin; Fibroblasts; Follow-Up Studies; Humans; Keratinocytes; Male; Middle Aged; Mohs Surgery; Pilot Projects; Time Factors; Treatment Outcome; Wound Healing

There is growing interest to application of regenerative medicine approaches in otorhinolaryngological practice, especially in the framework of the therapy of vocal fold (VF) scar lesions. The used conservative and surgical methods, despite the achieved positive outcomes, are frequently unpredictable and do not result in the restoration of the VF's lamina propria's structure, which provides the mechanical properties necessary for vibration. In this connection, the aim of this study was to ascertain the safety and efficacy of a bioequivalent in the treatment of VF scars using a rabbit model of chronic damage.. The bioequivalent consisted of a hydrogel system based on a PEG-fibrin conjugate and human bone marrow-derived MSC. It was characterized and implanted heterotopically into rats and orthotopically into rabbits after VF scar excision.. We showed that the fabricated bioequivalent consisted of viable cells retaining their metabolic and proliferative activity. While being implanted heterotopically, it had induced the low inflammatory reaction in 7 days and was well tolerated. The orthotopic implantation showed that the gel application was characterized by a lower hemorrhage intensity (p = 0.03945). The intensity of stridor and respiratory rate between the groups in total and between separate groups had no statistically significant difference (p = 0.96 and p = 1; p = 0.9593 and p = 0.97…1, respectively). In 3 days post-implantation, MSC were detected only in the tissues closely surrounding the VF defect. The bioequivalent injection caused that the scar collagen fibers were packed looser and more frequently mutually parallel that is inherent in the native tissue (p = 0.018). In all experimental groups, the fibrous tissue's ingrowth in the adjacent exterior muscle tissue was observed; however, in Group 4 (PEG-Fibrin + MSC), it was much less pronounced than it was in Group 1 (normal saline) (p = 0.008). The difference between the thicknesses of the lamina propria in the control group and in Group 4 was not revealed to be statistically significant (p = 0.995). The Young's modulus of the VF after the bioequivalent implantation (1.15 ± 0.25 kPa) did not statistically significantly differ from the intact VF modulus (1.17 ± 0.45 kPa); therefore, the tissue properties in this group more closely resembled the intact VF.. The developed bioequivalent showed to be biocompatible and highly efficient in the restoration of VF's tissue.

Topics: Animals; Cicatrix; Fibrin; Humans; Mesenchymal Stem Cell Transplantation; Rabbits; Rats; Regenerative Medicine; Vocal Cords

This paper describes a microscale fibroplasia and contraction model that is based on fibrin-embedded lung fibroblasts and provides a convenient visual readout of fibrosis. Cell-laden fibrin microgel drops are formed by aqueous two-phase microprinting. The cells deposit extracellular matrix (ECM) molecules such as collagen while fibrin is gradually degraded. Ultimately, the cells contract the collagen-rich matrix to form a compact cell-ECM spheroid. The size of the spheroid provides the visual readout of the extent of fibroplasia. Stimulation of this wound-healing model with the profibrotic cytokine TGF-β1 leads to an excessive scar formation response that manifests as increased collagen production and larger cell-ECM spheroids. Addition of drugs also shifted the scarring profile: the FDA-approved fibrosis drugs (nintedanib and pirfenidone) and a PAI-1 inhibitor (TM5275) significantly reduced cell-ECM spheroid size. Not only is the assay useful for evaluation of antifibrotic drug effects, it is relatively sensitive; one of the few in vitro fibroplasia assays that can detect pirfenidone effects at submillimolar concentrations. Although this paper focuses on lung fibrosis, the approach opens opportunities for studying a broad range of fibrotic diseases and for evaluating antifibrotic therapeutics.

Topics: Cells, Cultured; Cicatrix; Collagen; Extracellular Matrix; Fibrin; Fibroblasts; Fibrosis; Humans; Transforming Growth Factor beta1

High rates of structural failure are reported after rotator cuff repairs due to inability to recreate the native enthesis during healing. The development of biological augmentation methods that mitigate scar formation and regenerate the enthesis is still an unmet need. Since neonatal enthesis is capable of regeneration after injury, this study tested whether delivery of neonatal tendon progenitor cells (TPCs) into the adult injured environment can enhance functional and structural supraspinatus enthesis and tendon healing.. TPCs were isolated from Ai14 Rosa26-TdTomato mouse Achilles tendons and labeled using adenovirus-Cre. Fifty-two CB57BL/6J mice underwent detachment and acute repair of the supraspinatus tendon and received either a fibrin-only or TPC-fibrin gel. Immunofluorescence analysis was carried out to determine cellularity (DAPI), fibrocartilage (SOX9), macrophages (F4/80), myofibroblasts (α-smooth muscle actin), and scar (laminin). Assays for function (gait and biomechanical testing) and structure (micro-computed tomography imaging, picrosirius red/Alcian Blue staining, type I and III collagen staining) were carried out.. Analysis of TdTomato cells after injury showed minimal retention of TPCs by day 7 and day 14, with detected cells localized near the bursa and deltoid rather than the enthesis/tendon. However, TPC delivery led to significantly increased %Sox9+ cells in the enthesis at day 7 after injury and decreased laminin intensity across almost all time points compared to fibrin-only treatment. Similarly, TPC-treated mice showed gait recovery by day 14 (paw area and stride length) and day 28 (stance time), while fibrin-treated mice failed to recover gait parameters. Despite improved gait, biomechanical testing showed no differences between groups. Structural analysis by micro-computed tomography suggests that TPC application improves cortical thickness after surgery compared to fibrin. Superior collagen alignment at the neo-enthesis was also observed in the TPC-augmented group at day 28, but no difference was detected in type I and III collagen intensity.. We found that neonatal TPCs improved and restored functional gait by reducing overall scar formation, improving enthesis collagen alignment, and altering bony composition response after supraspinatus tendon repair. TPCs did not appear to integrate into the healing tissue, suggesting improved healing may be due to paracrine effects at early stages. Future work will determine the factors secreted by TPCs to develop translational targets.

Topics: Actins; Alcian Blue; Animals; Biomechanical Phenomena; Cicatrix; Collagen; Fibrin; Gait; Laminin; Mice; Rotator Cuff; Rotator Cuff Injuries; Stem Cells; Tendons; X-Ray Microtomography

An intriguing observation that has recently found support through clinical and experimental studies is that wounds of the oral mucosa tend to display faster healing and result in less scarring than in the skin. We aimed to investigate the potential of heterotopic oral mucosal fibroblasts in cutaneous wounds while determining the main differences between wounds conditioned with either the oral mucosa or dermis-derived human fibroblasts. A total of 48 nude mice were divided into four groups: control, sham, dermal fibroblast (DF), and oral fibroblast (OF). Fibroblasts were isolated, cultured, and seeded onto fibrin scaffolds for transfer to full-thickness dorsal wounds. Cell viability, wound area, healing rate, vascularization, cellular proliferation, dermal thickness, collagen architecture, and subtypes were evaluated. Both cell groups had a viability of 95% in fibrin gel prior to transfer. None of the wounds fully epithelialized on day 10, while all were epithelialized by day 21, which resulted in scars of different sizes and quality. Healing rate and scars were similar between the control and sham groups, whereas fastest healing and least scarring were noted in the OF group. Dermal thickness was highest in the DF group, which was also supported by highest levels of collagen types I and III. Proliferative cells and vascular density were highest in the OF group. DF result in healing through a thick dermal component, while oral fibroblasts result in faster healing and less scarring through potentially privileged angiogenic and regenerative gene expression.

Topics: Animals; Cell Proliferation; Cell Survival; Cicatrix; Collagen Type I; Collagen Type III; Dermis; Fibrin; Fibroblasts; Gels; Humans; Mice; Mouth Mucosa; Neovascularization, Physiologic; Re-Epithelialization

Topics: Adaptive Immunity; Angiogenesis Inducing Agents; Animals; Biomechanical Phenomena; Cicatrix; Fibrin; Heart; Humans; Hydrogels; Injections; Myocardial Infarction; Neovascularization, Physiologic; Rats, Sprague-Dawley; Vascular Endothelial Growth Factor A

Evaluation of fibrin role on cancer cells implantation in injured tissues and studying the molecular mechanism of cancer cell interaction with the peritoneal damage.. Mouse colon cancer (CT26) and human mesothelial cells (HMCs) were used. CT26 cells were implanted on injured peritoneal zones. Icodextrin was used as a lubricant. For in vitro studies, fibrin clots from human plasma were used. The cell-fibrin interaction was observed by optical, electronic, and confocal microscopies. Aprotinin was used as a plasmin inhibitor. Hemostasis impact quantified by (1) the fibrin degradation product D-Dimer and PAR expression in HMCs; (2) the expression of plasminogen activator (PA) and its inhibitor (PAI-1) in cancer cells by qPCR and in supernatants through ELISA after in vitro HMC incubation with 2U of thrombin for 24 h.. (i) Cancer cell lines were adhered and implanted into the wound area in vivo in both the incision and peeling zones of the peritoneum and on the fibrin network in vitro. (ii) Icodextrin significantly inhibited cancer nodule formation in the scar and the incision or peritoneal damaged zones after surgery. (iii) In in vitro studies, cancer cell interaction with the fibrin clot generated a lysed area, causing an increase in plasmin-dependent fibrinolysis measured by D-dimer levels in the supernatants that was inhibited by aprotinin. (iv) Aprotinin inhibited cell-fibrin interaction and invasion. (v) Thrombin upregulates PAI-1 and downregulates PA expression in HMC.. Injured tissues favor cancer cell implantation through generated fibrin. Fibrin-cancer cells adhesion can be inhibited by icodextrin.

Topics: Animals; Cell Adhesion; Cell Culture Techniques; Cell Line, Tumor; Cicatrix; Disease Models, Animal; Female; Fibrin; Fluorescent Antibody Technique; Humans; Mice; Neoplasm Transplantation; Peritoneum

The chronic wound in legs due to vascular abnormalities occurs in 1% to 2% of the adult population. The current treatments are unsatisfactory, and new approaches should be studied. We report in this article a case of a 52-year-old man with a chronic venous wound at the tibia, which has been conventionally treated for nine years. With six weeks of treatment with the autologous fibrin membrane, we were able to identify scar tissue and vascularization, which are characteristic of a healing process.

Topics: Chronic Disease; Cicatrix; Fibrin; Humans; Male; Middle Aged; Pilot Projects; Wound Healing

Following injury, skin activates a complex wound healing programme. While cellular and signalling mechanisms of wound repair have been extensively studied, the principles of epidermal-dermal interactions and their effects on wound healing outcomes are only partially understood. To gain new insight into the effects of epidermal-dermal interactions, we developed a multiscale, hybrid mathematical model of skin wound healing. The model takes into consideration interactions between epidermis and dermis across the basement membrane via diffusible signals, defined as activator and inhibitor. Simulations revealed that epidermal-dermal interactions are critical for proper extracellular matrix deposition in the dermis, suggesting these signals may influence how wound scars form. Our model makes several theoretical predictions. First, basal levels of epidermal activator and inhibitor help to maintain dermis in a steady state, whereas their absence results in a raised, scar-like dermal phenotype. Second, wound-triggered increase in activator and inhibitor production by basal epidermal cells, coupled with fast re-epithelialization kinetics, reduces dermal scar size. Third, high-density fibrin clot leads to a raised, hypertrophic scar phenotype, whereas low-density fibrin clot leads to a hypotrophic phenotype. Fourth, shallow wounds, compared to deep wounds, result in overall reduced scarring. Taken together, our model predicts the important role of signalling across dermal-epidermal interface and the effect of fibrin clot density and wound geometry on scar formation. This hybrid modelling approach may be also applicable to other complex tissue systems, enabling the simulation of dynamic processes, otherwise computationally prohibitive with fully discrete models due to a large number of variables.

Topics: Animals; Cicatrix; Dermis; Epidermis; Fibrin; Fibroblasts; Keratinocytes; Models, Biological; Wound Healing

Harvesting of autografts results in donor site morbidities and is limited in scenarios such as large total body surface area burns. In these instances, coverage is increased by meshing grafts at the expense of delayed biologic closure. Moreover, graft meshing increases the likelihood of contraction and hypertrophic scarring, limits range of motion, and worsens cosmesis. Many tissue engineering technologies have touted the promise of adipose-derived stem cells (ASCs) for burn wounds. The primary objective of the current study was to determine feasibility and efficacy of in situ ASC delivery via PEGylated fibrin (FPEG) hydrogels as adjuncts to meshed split thickness skin grafts in a porcine model. Deep partial thickness burns were created on the dorsum of anesthetized Yorkshire pigs, and subsequently debrided on post-burn day 4. After debridement, wounds were treated with: split thickness skin grafts (STSG); meshed STSG (mSTSG); and mSTSG + FPEG with increasing doses of ASCs. We show that FPEG hydrogels can be delivered in situ to prevent the contraction seen after meshing of STSG. Moreover, ASCs delivered in FPEG dose-dependently increase blood vessel size which significantly correlates with CD31 protein levels. The current study reports a dual-action adjunct therapy to autografting administered in situ, wherein FPEG acts as both scaffolding to prevent contraction, and as a delivery vehicle for ASCs to accelerate angiogenesis. This strategy may be used to incorporate other biologics for generating tissue engineered products aimed at improving wound healing and minimizing donor sites or scarring. Stem Cells Translational Medicine 2018;7:360-372.

Topics: Adipocytes; Animals; Autografts; Biocompatible Materials; Burns; Cicatrix; Debridement; Female; Fibrin; Hydrogels; Polyethylene Glycols; Skin; Skin Transplantation; Stem Cells; Swine; Transplantation, Autologous; Wound Healing

Many cell types remodel the extracellular matrix of the tissues they inhabit in response to a wide range of environmental stimuli, including mechanical cues. Such is the case in dermal wound healing, where fibroblast migrate into and remodel the provisional fibrin matrix in a complex manner that depends in part on the local mechanical environment and the evolving multi-scale mechanical interactions of the system. In this study, we report on the development of an image-based multi-scale mechanical model that predicts the short-term (24 hours), structural reorganization of a fibrin gel by fibroblasts. These predictive models are based on an in vitro experimental system where clusters of fibroblasts (i.e., explants) were spatially arranged into a triangular geometry onto the surface of fibrin gels that were subjected to either Fixed or Free in-plane mechanical constraints. Experimentally, regional differences in short-term structural remodeling and cell migration were observed for the two gel boundary conditions. A pilot experiment indicated that these small differences in the short-term remodeling of the fibrin gel translate into substantial differences in long-term (4 weeks) remodeling, particularly in terms of collagen production. The multi-scale models were able to predict some regional differences in remodeling and qualitatively similar reorganization patterns for the two boundary conditions. However, other aspects of the model, such as the magnitudes and rates of deformation of gel, did not match the experiments. These discrepancies between model and experiment provide fertile ground for challenging model assumptions and devising new experiments to enhance our understanding of how this multi-scale system functions. These efforts will ultimately improve the predictions of the remodeling process, particularly as it relates to dermal wound healing and the reduction of patient scarring. Such models could be used to recommend patient-specific mechanical-based treatment dependent on parameters such as wound geometry, location, age, and health.

Topics: Cell Communication; Cell Movement; Cell-Matrix Junctions; Cells, Cultured; Cicatrix; Collagen; Computer Simulation; Extracellular Matrix; Fibrin; Fibroblasts; Gels; Microspheres; Skin; Skin Physiological Phenomena; Wound Healing

This paper aimed to study the best working concentration of mitomycin C (MMC) fibrin gel on spinal peridural scar tissue in rats and the sustained release function of peridural adhesion after laminectomy of rats. 96 SD rats were divided into four groups. They were conducted L1 laminectomy and sprayed FG-MMC. The concentration of MMC was detected and the best working concentration of MMC was selected. Then other 48 SD rats were divided into four groups to construct L1 vertebral plate excision model. Materials were drawn 4 weeks after the operation for Rydell grading. In addition, we observed HE staining and fibroblast proliferation and collagen distribution situation after Masson staining. And concentration of hydroxyproline was also detected. The best working concentration of MMC experiment showed that except experimental group C, the other groups all appeared drug release peak in the 4th week after the operation. MMC concentration of group C appeared drug release peak in the 5th week besides the 2nd week. Moreover, adhesion of endorhachis and peripheral tissue in group A was the most obvious while the group C was the weakest. Experiment on the slow-release effect of different adhesion materials on peridural adhesion showed that compared to the contrast group and group F, Rydell grading in group E and G was Level 0 and with low adhesion degree, little fibroblast and fibrocyte, low collagen content, regular collagen fibers arrangement and no inflammatory cells after HE staning and Masson staining. In addition, content of hydroxyproline(HOP) decreased significantly especially the group of FG-MMC mixture. It was concluded that MMC fibrin gel mixture had a good slow-release effect on adhesion of spinal peridural scar tissue in rats and the best working concentration was 0.5 mg FG-MMC/ml.

Topics: Adhesiveness; Animals; Cicatrix; Fibrin; Gels; Hydroxyproline; Male; Mitomycin; Rats; Rats, Sprague-Dawley

Cutaneous wound contraction and epithelialization act collaboratively to minimize the exposed wound surface. However excessive wound contraction is undesirable due to the resultant disfigurement and scarring. Fibrin clot has greater stiffness than surrounding tissue and mechanical strain further enhances its stiffness. On the contrary, skin exhibits diminished stiffness when affected by high strain rates. Therefore during early stages of wound healing, the contractile wound border is confronted by fibrin clot forming a high strain region in the interface of contractile tissue and fibrin clot--which is evidenced by computer simulation. Due to the stress relaxation property of skin, the contractile strain is partly neutralized. Meanwhile, gradually the stiffness of fibrin clot decreases which is followed by another cycle of wound contraction. This cyclic pattern of contraction resembles the movement of a stone over water or "skipping stone". The stone bounces repeatedly when thrown across the surface of water with reduction of jumping altitude with each bounce till the stone stops completely. This hypothesis is further supported by the observed initial delay in wound contraction and the chronological correlation of enhanced wound contraction with loss of superficial eschar and substitution of fibrin clot with granulation tissue. Also there is evidence that fibrin inhibits fibroblast-mediated contraction of collagen. Furthermore, modest increase in wound contraction rate in fibrinogen deficient mice and fibrin-mediated diminished wound contraction are agreement with the proposed hypothesis.

Topics: Blood Coagulation; Blood Platelets; Cicatrix; Fibrin; Humans; Models, Cardiovascular; Skin; Wound Healing; Wounds, Penetrating

Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates geared to simplified preparation without biochemical blood handling. In this initial article, we describe the conceptual and technical evolution from fibrin glues to platelet concentrates. This retrospective analysis is necessary for the understanding of fibrin technologies and the evaluation of the biochemical properties of 3 generations of surgical additives, respectively fibrin adhesives, concentrated platelet-rich plasma (cPRP) and PRF. Indeed, the 3-dimensional fibrin architecture is deeply dependent on artificial clinical polymerization processes, such as massive bovine thrombin addition. Currently, the slow polymerization during PRF preparation seems to generate a fibrin network very similar to the natural one. Such a network leads to a more efficient cell migration and proliferation and thus cicatrization.

Topics: Animals; Blood Platelets; Cattle; Cell Separation; Cicatrix; Fibrin; Fibrin Tissue Adhesive; Gels; Hemostatics; Humans; Phase Transition; Platelet Aggregation; Wound Healing

Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates, with simplified processing and without biochemical blood handling. In this fourth article, investigation is made into the previously evaluated biology of PRF with the first established clinical results, to determine the potential fields of application for this biomaterial. The reasoning is structured around 4 fundamental events of cicatrization, namely, angiogenesis, immune control, circulating stem cells trapping, and wound-covering epithelialization. All of the known clinical applications of PRF highlight an accelerated tissue cicatrization due to the development of effective neovascularization, accelerated wound closing with fast cicatricial tissue remodelling, and nearly total absence of infectious events. This initial research therefore makes it possible to plan several future PRF applications, including plastic and bone surgery, provided that the real effects are evaluated both impartially and rigorously.

Topics: Blood Platelets; Bone Regeneration; Cell Movement; Cicatrix; Epithelium; Fibrin; Fibrin Tissue Adhesive; Fibroblasts; Gels; Hemostatics; Humans; Leukocytes; Mesenchymal Stem Cells; Neovascularization, Physiologic; Platelet Aggregation; Tooth Socket; Wound Healing

Burn wounds are characterised by central necrosis surrounded by an area of stasis with compromised perfusion. Secondary aggravation of the burn wound due to ischaemia in the zone of stasis can also result in necrosis. This study aims to improve circulation in the zone of stasis by reducing microthrombus formation and thereby to reduce secondary aggravation.. Recombinant nematode anticoagulant protein (rNAPc2) was administered to Wistar rats at 3 or 30 microg/kg as a single or daily dose. A comb pattern burn was induced on the dorsum of these rats and its evolution monitored by serial photography, planimetry, laser doppler flowmetry and immunohistochemistry.. In the 30 microg/kg daily group, extension of the burn wound was curbed, limiting the burn area to 1.99+/-0.67 cm(2) on day 28, compared to 3.51+/-0.37 cm(2) in the control group (p=0.015). Laser doppler evaluation showed a significant (p<0.001) increase in circulation in the first day post-burn. Significantly less (p<0.001) microvascular fibrin formation was observed by immunohistochemistry.. Anticoagulation with rNAPc2 improved perfusion of the burn wound. The resultant reduction in the area of the burn led to earlier healing and less scar contracture.

Topics: Animals; Anticoagulants; Burns; Cicatrix; Contracture; Fibrin; Flow Cytometry; Helminth Proteins; Male; Random Allocation; Rats; Rats, Wistar; Recombinant Proteins; Regional Blood Flow

The authors sought to determine the role of the plasminogen pathway in wound healing. They hypothesized that decreased fibrin degradation may lead to increased collagen deposition. Presuming that the degree of histopathological abnormality correlates with the aesthetic appearance of the scar, we conducted a study that attempted to determine the histopathological appearance of scar tissue in mice with and without impaired function of the plasminogen pathway.. Mice with and without deficiencies in the plasminogen pathway underwent surgery. The role of the plasminogen pathway in wound healing was studied by analysis of scar tissue formation using the methods described.. A 2-cm incision was made on the dorsum of mice with and without specified genetic deficiencies in the plasminogen pathway. After the animals were killed, the tissue was harvested, fixed, and prepared using hematoxylin and eosin as well as trichrome stains. Histopathological analysis and scoring were performed by two separate investigators in a blinded manner. Student's t test was used to determine statistical significance between groups.. A statistically significant difference in collagen orientation was noted between mice with impaired plasminogen pathway function and the wild-type (control) group (P =.0163). A statistical trend toward improved wound healing for plasminogen-deficient mice was found for overall histomorphological score (P =.0706).. The role of the plasminogen pathway in wound healing is one that should be noted and may lead to the development of new therapies that reduce scar tissue formation. Hence, the role of other thrombolytic and anti-thrombolytic agents in wound healing should be further investigated to precisely identify agents that play the most significant role in scar tissue formation.

Topics: Animals; Cicatrix; Collagen; Fibrin; Mice; Mice, Inbred C57BL; Mice, Knockout; Tissue Plasminogen Activator; Wound Healing

Proteolytic degradation of the provisional fibrin matrix and subsequent substitution by fibroblast-produced collagen are essential features of injury repair. Immunohistochemical studies revealed that although dermal fibroblasts of normal scars and keloids expressed both urokinase type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1), keloid fibroblasts had a much higher PAI-1 expression. In long-term three-dimensional fibrin gel cultures (the in vitro fibroplasia model), normal fibroblasts expressed moderate and modulated activity levels of uPA and PAI-1. In contrast, keloid fibroblasts expressed a persistently high level of PAI-1 and a low level of uPA. The high PAI-1 activity of keloid fibroblasts correlated with their elevated collagen accumulation in fibrin gel cultures. Substituting collagen for fibrin in the gel matrix resulted in increased uPA activity and reduced collagen accumulation of keloid fibroblasts. Furthermore, decreasing PAI-1 activity of keloid fibroblasts in fibrin gel cultures with anti-PAI-1-neutralizing antibodies also resulted in a reduction in collagen accumulation by keloid fibroblasts. Cumulatively, these results suggest that PAI-1 overexpression is a consistent feature of keloid fibroblasts both in vitro and in vivo, and PAI-1 may play a causative role in elevated collagen accumulation of keloid fibroblasts.

Topics: Adolescent; Adult; Cell Culture Techniques; Cells, Cultured; Child; Child, Preschool; Cicatrix; Collagen; Female; Fibrin; Fibroblasts; Humans; Keloid; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Racial Groups; Wound Healing

Topics: Algorithms; Bandages; Cicatrix; Debridement; Decision Trees; Fibrin; Humans; Macrophages; Skin Care; Wound Healing

We develop a novel mathematical model for collagen deposition and alignment during dermal wound healing. We focus on the interactions between fibroblasts, modelled as discrete entities, and a continuous extracellular matrix composed of collagen and a fibrin based blood clot. There are four basic interactions assumed in the model: fibroblasts orient the collagen matrix, fibroblasts produce and degrade collagen and fibrin and the matrix directs the fibroblasts and determines the speed of the cells. Several factors which influence the alignment of collagen are examined and related to current anti-scarring therapies using transforming growth factor beta. The most influential of these factors are cell speed and, more importantly for wound healing, the influx of fibroblasts from surrounding tissue.

Topics: Cicatrix; Collagen; Computer Simulation; Extracellular Matrix; Fibrin; Fibroblasts; Humans; Models, Biological; Skin; Wound Healing

Livedoid vasculitis is characterized clinically by smooth or depressed ivory-white scars surrounded by hyperpigmentation and telangiectasia with or without preceding purpuric infiltrated papules and plaques and histologically by intravascular deposition of fibrin. Its etiology remains obscure and therapy very difficult.. Our purpose was to test the efficacy of low-dose danazol in the treatment of livedoid vasculitis.. Seven patients with active lesions of livedoid vasculitis were treated with low-dose danazol (200 mg, orally, daily). Laboratory coagulation and fibrinolysis parameters, including antithrombin III, protein C, protein S, tissue plasminogen activator, plasminogen, alpha 2-antiplasmin and fibrinogen, were evaluated before and during the therapy.. Six of the 7 patients completed the treatment. After the therapy, all 6 patients had rapid cessation of new lesion formation, prompt reduction in their pain and healing of ulcers. A significant elevation of plasminogen and a decrease in fibrinogen levels were noted 1 month after initiation of the therapy (p = 0.028). The level of fibrinogen seemed to parallel the disease activity in individual patients. In addition, in most of these patients, the levels of antithrombin III, protein C, protein S and alpha 2-antiplasmin tended to increase after the treatment. However, the differences were not statistically significant. Abnormalities of tissue plasminogen activator levels were less consistent. Low-dose danazol was well tolerated without major side effects.. We concluded that low-dose danazol was effective in the treatment of livedoid vasculitis, without unacceptable side effects.

Topics: Administration, Oral; Adult; alpha-2-Antiplasmin; Antithrombin III; Blood Coagulation; Blood Vessels; Cicatrix; Danazol; Estrogen Antagonists; Female; Fibrin; Fibrinogen; Fibrinolysis; Humans; Hyperpigmentation; Male; Plasminogen; Protein C; Protein S; Purpura; Remission Induction; Safety; Skin Diseases, Vascular; Skin Ulcer; Telangiectasis; Tissue Plasminogen Activator; Vasculitis; Wound Healing

The clinical effects of the Nd:YAG laser in the rat skin as well as alterations of the extracellular matrix during healing were presented in this study.. This study evaluated the clinical effects of the Nd:YAG laser used with different energy parameters (low energy: 1.75 W and 20 pps/high energy: 3.0 W and 30 pps) in a duration 20-40 s in rat skin. Control incisions were performed with a scalpel blade. Rat skin incisions were examined over a period of 28 days by clinical photographs as well as by using immunohistochemical techniques in order to find the distribution and the amount of the extracellular matrix fibrillar components, i.e., collagen types I and III.. Low energy laser treatment caused a rapid wound healing without scar tissue formation (compared to the high energy laser group) and clinical signs of scar tissue formation (compared to control incisions with the conventional scalpel). During the study period, the laser-induced lesions healed through reparative synthesis of the matrix proteins, which led to filling of the tissue defects. The regenerative processes were similar in the low-energy laser group and in the control incisions. In the high-energy lased tissues, we observed a delayed replacement of the defects by newly formed extracellular matrix proteins.. This study showed a slower wound healing in the high-energy lased tissues. A similar healing in the low-energy lased tissues and in the incisions with the conventional scalpel was observed. The differences in the distribution of matrix proteins during healing and the coagulation of the tissues, which were exposed to low-energy laser treatment, might be the explanation for the minimal scarring, contraction, and pigmentation of the lased tissues as compared to conventional incisions.

Topics: Aluminum Silicates; Animals; Cicatrix; Collagen; Dermatologic Surgical Procedures; Epithelium; Extracellular Matrix; Extracellular Matrix Proteins; Fibrin; Immunohistochemistry; Laser Coagulation; Male; Neodymium; Photography; Rats; Regeneration; Skin; Skin Pigmentation; Time Factors; Wound Healing; Yttrium

According to the conventional hypothesis and its variants, wound granulation tissue is formed by the proliferation and the migration of two closely cooperating but separated cell systems: the endothelial and the fibroblastic (including pericytes). While the elaborated theory of angiogenesis explains the former, there is not a similar theory concerning the latter. The recently proposed angiogenic hypothesis of repair and fibrosis unifies both cell systems by proposing endothelial origin for fibroblastic cells. It was formed on the basis of hyperplastic capillaries and vascular endothelium derived fibroblastic cells in chronic fibrotic diseases. The recent description of hyperplastic capillary sprouts in experimental fibrin clots confirms the validity of this hypothesis also in healing by primary and secondary intentions.

Topics: Angiogenesis Inducing Agents; Animals; Capillaries; Cell Differentiation; Cicatrix; Endothelium, Vascular; Fibrin; Fibroblasts; Fibrosis; Growth Substances; Humans; Hyperplasia; Neovascularization, Pathologic; Wound Healing

Strabismus surgery sometimes fails because of the mechanical restriction caused by the development of fibrous adhesions between the operated muscle and the surrounding tissues. Reoperation increases the frequency and severity of mechanical restriction significantly because of additional scar formation. Attempts to isolate the muscle from other tissues using gelatin sponges or Supramid plastic sleeves have been unsuccessful because of the body's reaction to these permanent foreign bodies. We used an ultra-pure fraction of sodium hyaluronate to study whether this nonantigenic, noninflammatory, viscoelastic substance could function as a temporary sleeve to prevent or reduce scarring and mechanical restriction following strabismus surgery. We resected the superior rectus muscle of 14 eyes from seven 5- to 7-pound white rabbits. In one eye, we instilled sodium hyaluronate 1% around the muscle. The other eye served as a control. The rabbits were killed at five, seven, ten, 14, 21, 28, and 42 days. Ante mortem length-tension measurements and post mortem histologic examinations of the operated muscles were performed in a blinded fashion. The results suggested, but did not definitely demonstrate, that sodium hyaluronate may reduce postoperative adhesions.

Topics: Animals; Cicatrix; Collagen; Fibrin; Hyaluronic Acid; Oculomotor Muscles; Postoperative Complications; Rabbits; Strabismus; Tissue Adhesions

Immunoglobulins A, G, and M were localized in normal skin, hypertrophic scars, keloids, and mature scars by the direct immunofluorescent antibody method. All three immunoglobulins appeared increased in the lesions above levels observed in normal skin. Extractions of the immunoglobulins from the same type of tissues also suggested an increase above levels from normal skin. The data suggest attritional leakage of several plasma proteins from the microvasculature in the lesions. No one immunoglobulin appears significantly increased in the lesions compared with others.

Topics: Albumins; Cicatrix; Complement C3; Complement C4; Fibrin; Fluorescent Antibody Technique; Humans; Hypertrophy; Immunoglobulins; Keloid; Skin

Central full-thickness perforating excision wounds were made in rabbit corneas and were examined by light and scanning electron microscopy at various times after wounding to study the three-dimensional morphologic changes in the tissue during healing and remodeling. Formation of a fibrin clot soon after wounding seals the hole and functions as a substrate for the healing epithelium. Changes in the histologic appearance of the fibrin lot immediately below the new epithelium are followed by migration of adjacent stromal cells under the epithelium, parallel to the basal surface of this tissue. Further healing is characterized by the organization of stromal fibroblasts into several layers parallel to the corneal surface and the deposition of collagen as a matted meshwork of fibrils tangential to the cell surface. Although remodeling of the collagenous matrix of corneal scar is evident and the scar eventually appears less opaque, the lamellae of the scar are narrower and shorter than normal. Evidence from this and other studies suggests that the orientation of the fibroblasts in healing tissues is determined by the organization of the newly formed epithelium. Furthermore, our observations are consistent with the hypothesis that collagen fibrils are deposited parallel to the flat surface of the fibroblasts during scar formation. Subsequent reorganization of this collagenous matrix approaches the normal lamellar appearance, but the matrix fails to regenerate even after 2 years.

Topics: Animals; Cicatrix; Collagen; Cornea; Epithelium; Fibrin; Fibroblasts; Microscopy, Electron, Scanning; Rabbits; Wound Healing

Topics: Adolescent; Burns; Child; Cicatrix; Cytoplasm; Fibrin; Fibroblasts; Granulation Tissue; Humans; Hypertrophy; Infant

In animal experiments the additional sealing of colonic anastomoses using fibrin glue resulted in especially fast healing with formation of a delicate scar. Between April 1, 1976 and March 31, 1977, this method was used in 118 out of 355 patients undergoing extensive abdominal procedures. Suture line leakage was seven times less frequent than in the control group. This resulted in a considerable decrease of postoperative mortality.

Topics: Animals; Cicatrix; Colon; Dogs; Esophagus; Fibrin; Postoperative Complications; Stomach; Suture Techniques; Tissue Adhesives; Wound Healing

The study includes 40 cases of skin replacement performed by an ophthalmologist over a period of 4 years. An absorbable implant material, Bioplast fibrin, was used as a graft following the extirpation of 12 eyelid tumors, the treatment of eight fresh, destructive skin injuries, and the removal of deforming scars around the eyes, in 20 cases. The biocompatible implant provided barrier properties preventing infection or excessive fluid loss. The resorption rate was adjusted to 3-4 weeks. These grafts were gradually replaced by new epithelial tissue growing in from the periphery of the wound edge. The new tissue had the elasticity and cosmetic appearance of surrounding skin. Thus, small periorbital skin tumors can now be removed without the necessity of doing a split thickness skin graft to cover the defect.

Topics: Adolescent; Adult; Aged; Biocompatible Materials; Cicatrix; Dermatologic Surgical Procedures; Eye Injuries; Eyelid Neoplasms; Female; Fibrin; Granuloma; Humans; Male; Middle Aged; Skin; Skin Diseases

Of 144 patients with bullous or cicatricial pemphigoid, nine with localized pemphigoid were seen at the Mayo Clinic between 1968 and 1975. In two patients the disease had become generalized before presentation, and in one it had evolved into bullous pemphigoid, the only case with positive indirect immunofluorescence. One additional patient showed mucosal lesions. Direct immunofluorescence was performed in five patients and showed linear deposition of C3 and fibrin but not immunoglobulins in three; in two patients immunofluorescence was negative. Localized pemphigoid can be divided into two types: that with scarring plaque-like lesions usually occurring on the head and neck predominantly in males, and that with localized bullous lesions usually occurring on the lower part of the legs of females.

Topics: Adult; Aged; Biopsy; Cicatrix; Complement C3; Female; Fibrin; Fluorescent Antibody Technique; Humans; Male; Middle Aged; Skin Diseases, Vesiculobullous

Topics: Animals; Cicatrix; Fibrin; Fibroblasts; Haplorhini; Iris; Leukocytes; Macaca; Macrophages; Microscopy, Electron; Phagocytosis; Pigments, Biological; Suture Techniques

Topics: Cicatrix; Epithelial Cells; Fibrin; Gastric Juice; Gastric Mucosa; Granulation Tissue; Humans; Necrosis; Peptic Ulcer Perforation; Stomach Ulcer

Topics: Animals; Anti-Bacterial Agents; Cerebellum; Chloroquine; Cicatrix; Dogs; Dura Mater; Female; Fibrin; Membranes, Artificial; Nylons; Ointments; Paper; Spinal Cord; Transplantation, Autologous; Trypsin

In 81 patients with fibrous intra-abdominal adhesions there was a high incidence of other lesions in which there was a substantial element of fibrosis. These included chronic peptic ulceration, ovarian cysts, fibrous stenotic lesions, and thickened scars. It is suggested that in some patients a generalized fibrotic tendency as well as local factors may play a part in the pathogenesis of adhesions.

Topics: Abdomen; ABO Blood-Group System; Adult; Aged; Chronic Disease; Cicatrix; Constriction; Female; Fibrin; Fibrinolysis; Humans; Male; Middle Aged; Ovarian Cysts; Peptic Ulcer; Tissue Adhesions