Angiogenesis induction and regression in human surgical wounds

Brown, Nicola J.; Smyth, E.; Cross, Simon S.; Reed, Malcolm

doi:10.1046/j.1524-475x.2002.10408.x

Cited by 89 publications

(72 citation statements)

References 30 publications

(30 reference statements)

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“…These wounds are useful from an experimental perspective in that their size and depth can be precisely controlled. As they involve all the components of the healing process, they provide an excellent research tool and have been used to investigate angiogenesis (37)(38)(39), wound contraction, and closure (40,41). This model has also been used to investigate the effects of new treatments on wound healing.…”

Section: Animal Models Of Wound Healingmentioning

confidence: 99%

Models of wound healing: an emphasis on clinical studies

Wilhelm

Wilhelm²,

Bielfeldt³

2016

Skin Research and Technology

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Background: The healing of wounds has always provided challenges for the medical community whether chronic or acute. Understanding the processes which enable wounds to heal is primarily carried out by the use of models, in vitro, animal and human. It is generally accepted that the use of human models offers the best opportunity to understand the factors that influence wound healing as well as to evaluate efficacy of treatments applied to wounds. Objectives: The objective of this article is to provide an overview of the different methodologies that are currently used to experimentally induce wounds of various depths in human volunteers and examines the information that may be gained from them. Methods: There is a number of human volunteer healing models available varying in their invasiveness to reflect the different possible depth levels of wounds.Results: Currently available wound healing models include sequential tape stripping, suction blister, abrasion, laser, dermatome, and biopsy techniques. The various techniques can be utilized to induce wounds of variable depth, from removing solely the stratum corneum barrier, the epidermis to even splitthickness or full thickness wounds. Conclusion: Depending on the study objective, a number of models exist to study wound healing in humans. These models provide efficient and reliable results to evaluate treatment modalities. I N VITRO studies and animal models have provided useful information for many breakthroughs and medical advances. However, these are not always appropriate and in many cases are inadequate for discovering the actual pathology responsible. While animal models are suitable for many skin disorders and diseases, they do have their limitations when wound healing is being investigated. The complex biological pathway that occurs during wound healing is not always mirrored in animal models and human models need to be considered. In the case of chronic wound pathology, human models are not always good predictors but they do provide a good understanding of acute wound pathology. Because of the difficulty in obtaining suitable volunteers with chronic wounds and incorporating them into a study, human acute wound models provide the best opportunity to understand the wound healing process and the performance of different products that assist and promote wound healing. This paper evaluates the different wound healing models and discusses the potential for these models to be suitable predictors of wound healing.

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Section: Animal Models Of Wound Healingmentioning

confidence: 99%

Models of wound healing: an emphasis on clinical studies

Wilhelm

Wilhelm²,

Bielfeldt³

2016

Skin Research and Technology

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“…3B and 3C). This process is initially influenced by cytokines and growth factors, such as VEGF+, culminating with the advent of new blood vessels, which transport nutrients and inflammatory cells, accelerating the recovery of damaged tissue (Brown et al, 2002). Thus, we can then infer that the latex pro-inflammatory properties have a direct impact on their ability to modulate the scarring process.…”

Section: Discussionmentioning

confidence: 99%

Involvement of mast cells, CD68+ and VEGF+ expressions in response to Himatanthus drasticus commercial latex in mice wound healing model

Santos

Ferreira

Rodrigues

et al. 2017

Arq. Bras. Med. Vet. Zootec.

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This study aimed to evaluate Himatanthus drasticus latex in a mice wound healing experimental model. Animals were divided into four groups (n=7) according to the treatments: GI -saline 0.9% (control), GIImineral oil (vehicle), GIII -H. drasticus commercial latex (HdCL) and GIV -H. drasticus mixed isolated fraction (MIF, 1 mg/mL). The treatments were applied topically once daily, 50 µL for 14 consecutive days. Macroscopic lesions were evaluated, considering parameters such as swelling, redness, granulation tissue and reepithelialization. VEGF+, CD68+ expressions and mast cells (Toluidin blue stain) were evaluated. HdCL induced higher contraction and exuberant granulation tissue (P > 0.05). HdCL showed a mild inflammatory process while MIF induced intense infiltrate inflammatory predominantly by lymphocytes, vascular congestion, bleeding and did not presented full reepithelialization. Reorganization of collagen fibers (red picrosirius stain) was observed. CD68+ expression and mast cells were presented as moderate, intense and mild in GI, GIII and GIV, respectively. Neovascularization occurred in all groups, while VEGF+ expression was intense in MIF in relation to HdCL. We concluded that HdCL presents wound healing potential, through modulation of mast cells, CD68+ and VEGF+ expressions that can be associated to triterpenes presence according MIF isolated from HdCL.Keywords: latex, Apocinaceae, wound healing, angiogenesis, inflammatory infiltrate RESUMO Objetivou-se avaliar o látex de Himatanthus drasticus em feridas induzidas experimentalmente em camundongos. Os animais foram divididos em quatro grupos (n=7): GI -salina 0,9% (controle), GIIóleo mineral (veículo), GIII -látex comercial de H. drasticus (HdCL) e GIV -fração isolada mista de H. drasticus (MIF, 1mg/mL). Os tratamentos foram aplicados topicamente uma vez ao dia (50µL), durante 14 dias consecutivos. Lesões macroscópicas, as expressões de VEGF+, CD68+ e a participação dos mastócitos (coloração azul de toluidina) foram avaliadas. HdCL induziu maior contração e tecido de granulação exuberante (P >0,05). HdCL induziu leve processo inflamatório enquanto MIF promoveu intenso infiltrado inflamatório predominantemente linfocítico, congestão vascular, hemorragia e reepitelização parcial. Observou-se reorganização das fibras colágenas (coloração picrosírius

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“…In our own experiments in normoglycemic mice, significantly higher vessel densities were found in primed animals on the day of surgery and on day 17 after surgery. Numerous studies have indicated that vascular regression is probably a regulated process in wound healing, with endothelial cells undergoing apoptosis [24,25]. Different matrix metalloproteinases and plasminogen have been shown to induce vascular regression during the formation of highly vascularized granulation tissue [25], and a long-lasting period of angiogenesis has been observed to comprise of the remodeling phase and maturation of wounds [26,27].…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies have indicated that vascular regression is probably a regulated process in wound healing, with endothelial cells undergoing apoptosis [24,25]. Different matrix metalloproteinases and plasminogen have been shown to induce vascular regression during the formation of highly vascularized granulation tissue [25], and a long-lasting period of angiogenesis has been observed to comprise of the remodeling phase and maturation of wounds [26,27]. Therefore, proangiogenic priming mimics the physiological continuum of vessel induction and vessel regression, which is in contrast to the permanent angiogenic stimuli occurring during topical treatment.…”

Section: Discussionmentioning

confidence: 99%

Priming with a Combination of Proangiogenic Growth Factors Enhances Wound Healing in Streptozotocin-Induced Diabetes in Mice

et al. 2011

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Background: Numerous proangiogenic growth factors have been shown to improve impaired wound healing. This study evaluated the effects of subcutaneous pretreatment with a combination of proangiogenic growth factors on wound closure, mechanical properties, vessel density, and morphology. Methods: Thirty-six Balb/c mice with streptozotocin-induced diabetes were divided into 3 groups. A mixture of VEGF (35.0 µg), bFGF (2.5 µg), and PDGF (3.5 µg) was administered subcutaneously 3, 5, and 7 days prior to wounding in the first group, whereas the second group received three doses of 3.5 µg PDGF. Wound sizes were assessed daily and the repaired tissues were harvested 7 days after wound closure. Results: Complete closure (≧95% healing of initial wound area) was reached in all proangiogenic pretreated animals by day 17, whereas the PDGF monotherapy group needed up to 20 days for complete closure. By the time of tissue harvesting on day 24, complete closure was not reached in all control animals. Punch biopsy material revealed 1.6-fold higher vessel densities in the proangiogenic combination-pretreated group than in the controls. Conclusions: Proangiogenic priming revealed several significant effects on diabetic wound healing: faster time to closure, a higher vessel density, and improved functional outcome.

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Angiogenesis induction and regression in human surgical wounds

Cited by 89 publications

References 30 publications

Models of wound healing: an emphasis on clinical studies

Models of wound healing: an emphasis on clinical studies

Involvement of mast cells, CD68+ and VEGF+ expressions in response to Himatanthus drasticus commercial latex in mice wound healing model

Priming with a Combination of Proangiogenic Growth Factors Enhances Wound Healing in Streptozotocin-Induced Diabetes in Mice

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