scholarly journals A mathematical model for collagen fibre formation during foetal and adult dermal wound healing

1996 ◽  
Vol 263 (1370) ◽  
pp. 653-660 ◽  
Keyword(s):  
Mathematical Model ◽  
Wound Healing ◽  
Transforming Growth Factor ◽  
Collagen Fibre ◽  
Transforming Growth Factor Β ◽  
Scar Tissue ◽  
A Value ◽  
Fibre Formation ◽  
The Difference ◽  
Dermal Wound

Adult dermal wounds, in contrast to foetal wounds, heal with the formation of scar tissue. A crucial factor in determining the nature of the healed tissue is the ratio of collagen 1 to collagen 3, which regulates the diameter of collagen fibres. We develop a mathematical model which focuses on the stimulus for collagen synthesis due to the secretion of the different isoforms of the regulatory chemical transforming growth factor β. Numerical simulations of the model lead to a value of this ratio consistent with that of healthy tissue for the foetus but corresponding to scarring in adult wound healing. We investigate the effect of topical application of TGFβ isoforms during healing and determine the key parameters which control the difference between adult and foetal repair.

Effects of Avotermin (Transforming Growth Factor β3) in a Clinically Relevant Pig Model of Long, Full-Thickness Incisional Wounds

2010 ◽  
Vol 14 (5) ◽  
pp. 223-232 ◽  
Author(s):  
Hugh G. Laverty ◽  
Nick L. Occleston ◽  
Mark Johnson ◽  
John Little ◽  
Richard Jones ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Clinical Parameters ◽  
Full Thickness ◽  
Relevant Model ◽  
Normal Wound Healing ◽  
Surgical Incisions ◽  
Dermal Wound

Background: The pig is an accepted species for evaluating the safety of molecules in dermal wound healing indications; however, the sizes of wounds assessed have not always been comparable to large incisions encountered clinically. Objective: To develop a clinically relevant model of incisional wounding in the Göttingen minipig for assessing the safety and tolerance of compounds in development to improve scarring. Methods: Intradermal avotermin (recombinant transforming growth factor β3 [TGFβ3]) up to 6,000 ng/100μL was administered twice to 20 cm full-thickness incisions. Results: Incisions were well tolerated in the minipig. Avotermin treatment was not associated with adverse changes in a range of clinical parameters, including wound healing and strength. Plasma TGFβ3 levels were transient with ≈0.1% bioavailability. Conclusion: A clinically relevant model of long, full-thickness, sutured surgical incisions in the minipig is achievable. Avotermin is well tolerated in this model and does not adversely affect normal wound healing at levels that significantly exceed those doses to be used clinically in humans.

scholarly journals A mathematical model of wound healing and subsequent scarring

2009 ◽  
Vol 7 (42) ◽  
pp. 19-34 ◽  
Author(s):  
B. D. Cumming ◽  
D. L. S. McElwain ◽  
Z. Upton
Keyword(s):  
Wound Healing ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Dermal Wound Healing ◽  
Hybrid Approaches ◽  
Complex Process ◽  
Representation Techniques ◽  
Dermal Wound ◽  
Size Scales

Wound healing is a complex process involving the delicate interaction between elements that vary widely in nature and size scales, from the nanometre level, such as molecules, to cells measured in micrometres, and fibres with width and length measured on both scales. Hybrid approaches, where each species is represented by a model on an appropriate size scale, have received attention recently. In this study, we provide a review of earlier work on such hybrid models of wound healing. General models for each of the element types involved in dermal wound healing used in this research are described: cells, modelled as discrete individuals; chemicals, modelled as continua; and fibres, modelled with a novel tensorial representation. Techniques for integrating such disparate models are outlined. A six-species model (fibrin, collagen, macrophages, fibroblasts, transforming growth factor-β (TGF-β) and tissue plasminogen activator) of dermal wound healing is presented. The role of the cytokine TGF-β in the healing cascade is investigated using the model, along with its role in the degree of scarring in the healed tissue.

scholarly journals A pulsatile release platform based on photo-induced imine-crosslinking hydrogel promotes scarless wound healing

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jian Zhang ◽  
Yongjun Zheng ◽  
Jimmy Lee ◽  
Jieyu Hua ◽  
Shilong Li ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Repair ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Skin Wound ◽  
Large Animal ◽  
Skin Wounds ◽  
Tgfβ Signaling ◽  
Pulsatile Release ◽  
Ecm Extracellular Matrix

AbstractEffective healing of skin wounds is essential for our survival. Although skin has strong regenerative potential, dysfunctional and disfiguring scars can result from aberrant wound repair. Skin scarring involves excessive deposition and misalignment of ECM (extracellular matrix), increased cellularity, and chronic inflammation. Transforming growth factor-β (TGFβ) signaling exerts pleiotropic effects on wound healing by regulating cell proliferation, migration, ECM production, and the immune response. Although blocking TGFβ signaling can reduce tissue fibrosis and scarring, systemic inhibition of TGFβ can lead to significant side effects and inhibit wound re-epithelization. In this study, we develop a wound dressing material based on an integrated photo-crosslinking strategy and a microcapsule platform with pulsatile release of TGF-β inhibitor to achieve spatiotemporal specificity for skin wounds. The material enhances skin wound closure while effectively suppressing scar formation in murine skin wounds and large animal preclinical models. Our study presents a strategy for scarless wound repair.

scholarly journals Simple Modelling of Extracellular Matrix Alignment in Dermal Wound Healing I. Cell Flux Induced Alignment

1998 ◽  
Vol 1 (3) ◽  
pp. 175-192 ◽  
Author(s):  
Luke Olsen ◽  
Philip K. Maini ◽  
Jonathan A. Sherratt ◽  
Ben Marchant
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Cell Movement ◽  
Collagen Fibre ◽  
Cell Types ◽  
Travelling Wave ◽  
Generic Model ◽  
Dimensional Version ◽  
Healing Wounds ◽  
Dermal Wound

We present a generic model to investigate alignment due to cell movement with spefic application to collagen fibre alignment in wound healing. In particular, alignment in two orthogonal directions is considered. Numerical simulation are presented to show how alignment is affected by key parameter min the model. from a travelling wave analysis of a simplified one-dimensional version of the model we derive a first order ordinary differential equation to describe the time evolution of aligment. We conclude that in the wound healing context,faster healing wounds result in more aligment and hence more serve scarring. It is shown how the model can be extended to included orientation dependent Kinetics,multipkle cell types and several extracellular matrix materials.

Cellular inhibitor of apoptosis protein 2 controls human colonic epithelial restitution, migration, and Rac1 activation

2015 ◽  
Vol 308 (2) ◽  
pp. G92-G99 ◽  
Author(s):  
Jakob Benedict Seidelin ◽  
Sylvester Larsen ◽  
Dorte Linnemann ◽  
Ben Vainer ◽  
Mehmet Coskun ◽  
...  
Keyword(s):  
Wound Healing ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Human Colon ◽  
Inhibitor Of Apoptosis ◽  
Experimental Ulcer ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptosis Protein

Identification of pathways involved in wound healing is important for understanding the pathogenesis of various intestinal diseases. Cellular inhibitor of apoptosis protein 2 (cIAP2) regulates proliferation and migration in nonepithelial cells and is expressed in human colonocytes. The aim of the study was to investigate the role of cIAP2 for wound healing in the normal human colon. Wound tissue was generated by taking rectosigmoidal biopsies across an experimental ulcer in healthy subjects after 5, 24, and 48 h. In experimental ulcers, the expression of cIAP2 in regenerating intestinal epithelial cells (IECs) was increased at the wound edge after 24 h ( P < 0.05), returned to normal after reepithelialization, and correlated with the inflammatory reaction in the experimental wounds ( P < 0.001). cIAP2 was induced in vitro in regenerating Caco2 IECs after wound infliction ( P < 0.01). Knockdown of cIAP2 caused a substantial impairment of the IEC regeneration through inhibition of migration ( P < 0.005). cIAP2 overexpression lead to formation of migrating IECs and upregulation of expression of RhoA and Rac1 as well as GTP-activation of Rac1. Transforming growth factor-β1 enhanced the expression of cIAP2 but was not upregulated in wounds in vivo and in vitro. NF-κB and MAPK pathways did not affect cIAP2 expression. cIAP2 is in conclusion a regulator of human intestinal wound healing through enhanced migration along with activation of Rac1, and the findings suggest that cIAP2 could be a future therapeutic target to improve intestinal wound healing.

Polymeric Nanofibre Scaffold for the Delivery of a Transforming Growth Factor β1 Inhibitor

2017 ◽  
Vol 70 (3) ◽  
pp. 280 ◽  
Author(s):  
Vipul Agarwal ◽  
Fiona M. Wood ◽  
Mark Fear ◽  
K. Swaminathan Iyer
Keyword(s):  
Tissue Engineering ◽  
Wound Healing ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Normal Skin ◽  
Scar Tissue ◽  
Transforming Growth Factor Β1 ◽  
Collagen I ◽  
Elevated Concentration ◽  
Skin Wound Healing

Skin scarring is a highly prevalent and inevitable outcome of adult mammalian wound healing. Scar tissue is both pathologically and aesthetically inferior to the normal skin owing to elevated concentration of highly orientated collagen I architecture in the innate repaired tissue. With highly invasive surgery being the main treatment modality, there is a great need for alternative strategies to mitigate the problem of scar formation. Tissue engineering approaches using polymeric scaffolds have shown tremendous promise in various disease models including skin wound healing; however, the problem of skin scarring has been greatly overlooked. Herein, we developed an electrospun poly(glycidyl methacrylate) (ES-PGMA) scaffold incorporating a small-molecule antiscarring agent, PXS64. PXS64, a lipophilic neutral analogue of mannose-6-phosphate, has been shown to inhibit the activation of transforming growth factor β1 (TGFβ1). TGFβ1 is a primary protein cytokine regulating the expression of collagen I during wound healing and therefore governs the formation of scar tissue. The nanofibres were tested for biocompatibility as a tissue engineering scaffold and for their efficacy to inhibit TGFβ1 activation in human dermal skin fibroblasts.

scholarly journals Proteolytic Release of Latent Transforming Growth Factor-β (TGF-β) Binding Protein-1 (LTBP-1) Fragment in Wound Healing

2009 ◽  
Vol 55 (3) ◽  
pp. 468-472
Author(s):  
Koji Mizuno ◽  
Hiroshi Wachi ◽  
Zenzo Isogai ◽  
Masahiko Yoneda ◽  
Satoshi Fujii ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Binding Protein ◽  
Transforming Growth Factor Β

scholarly journals The extracellular matrix: an active or passive player in fibrosis?

2011 ◽  
Vol 301 (6) ◽  
pp. G950-G955 ◽  
Author(s):  
Thomas N. Wight ◽  
Susan Potter-Perigo
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Transforming Growth Factor Β ◽  
Cytokine Signaling ◽  
Wound Healing Process ◽  
Inflammatory Stimuli ◽  
Specialized Form ◽  
Excessive Accumulation

Fibrosis is characterized by excessive accumulation of collagen and other extracellular matrix (ECM) components, and this process has been likened to aberrant wound healing. The early phases of wound healing involve the formation of a provisional ECM containing fibrin, fibrinogen, and fibronectin. Fibroblasts occupy this matrix and proliferate in response to activators elaborated by leukocytes that have migrated into the wound and are retained by the ECM. This coincides with the appearance of the myofibroblast, a specialized form of fibroblast whose differentiation is primarily driven by cytokines, such as transforming growth factor-β (TGF-β), and by mechanical tension. When these signals are reduced, as when TGF-β secretion is reduced, or as in scar shrinkage, myofibroblasts undergo apoptosis, resulting in a collagen-rich, cell-poor scar. Retention of myofibroblasts in fibrosis has been described as the result of imbalanced cytokine signaling, especially with respect to levels of activated TGF-β. ECM components can regulate myofibroblast persistence directly, since this phenotype is dependent on extracellular hyaluronan, tenascin-C, and the fibronectin splice variant containing the “extra domain A,” and also, indirectly, through retention of TGF-β-secreting cells such as eosinophils. Thus the ECM is actively involved in both cellular and extracellular events that lead to fibrosis. Targeting components of the ECM as cells respond to injury and inflammatory stimuli holds promise as a means to avoid development of fibrosis and direct the wound-healing process toward reestablishment of a healthy equilibrium.

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