Philipp Babilas

Oxygen in acute and chronic wound healing

Oxygen is a prerequisite for successful wound healing due to the increased demand for reparative processes such as cell proliferation, bacterial defence, angiogenesis and collagen synthesis. Even though the role of oxygen in wound healing is not yet completely understood, many experimental and clinical observations have shown wound healing to be impaired under hypoxia. This article provides an overview on the role of oxygen in wound healing and chronic wound pathogenesis, a brief insight into systemic and topical oxygen treatment, and a discussion of the role of wound tissue oximetry. Thus, the aim is to improve the understanding of the role of oxygen in wound healing and to advance our management of wound patients.

Wound healing in the 21st century

Delayed wound healing is one of the major therapeutic and economic issues in medicine today. Cutaneous wound healing is an extremely well-regulated and complex process basically divided into 3 phases: inflammation, proliferation, and tissue remodeling. Unfortunately, we still do not understand this process precisely enough to give direction effectively to impaired healing processes. There have been many new developments in wound healing that provide fascinating insights and may improve our ability to manage clinical problems. Our goal is to acquaint the reader with selected major novel findings about cutaneous wound healing that have been published since the beginning of the new millennium. We discuss advances in areas such as genetics, proteases, cytokines, chemokines, and regulatory peptides, as well as therapeutic strategies, all set in the framework of the different phases of wound healing.

Cytokines, chemokines and growth factors in wound healing.

In wound healing, a variety of mediators have been identified throughout the years. The mediators discussed here comprise growth factors, cytokines and chemokines. These mediators act via multiple (specific) receptors to facilitate wound closure. As research in the last years has led to many new findings, there is a need to give an overview on what is known, and on what might possibly play a role as a molecular target for future wound therapy. This review aims to keep the reader up to date with selected important and novel findings regarding growth factors, cytokines and chemokines in wound healing.

Intense pulsed light (IPL): A review

Intense pulsed light (IPL) devices use flashlamps and bandpass filters to emit polychromatic incoherent high‐intensity pulsed light of determined wavelength spectrum, fluence, and pulse duration. Similar to lasers, the basic principle of IPL devices is a more or less selective thermal damage of the target. The combination of prescribed wavelengths, fluences, pulse durations, and pulse intervals facilitates the treatment of a wide spectrum of skin conditions.

Photodynamic therapy in dermatology: state‐of‐the‐art

Photodynamic therapy (PDT) has become an established treatment modality for dermatooncologic conditions like actinic keratosis, Bowens disease, in situ squamous cell carcinoma and superficial basal cell carcinoma. There is also great promise of PDT for many non‐neoplastic dermatological diseases like localized scleroderma, acne vulgaris, granuloma anulare and leishmaniasis. Aesthetic indications like photo‐aged skin or sebaceous gland hyperplasia complete the range of applications. Major advantages of PDT are the low level of invasiveness and the excellent cosmetic results. Here, we review the principal mechanism of action, the current developments in the field of photosensitizers and light sources, practical aspects of topical PDT and therapeutical applications in oncologic as well as non‐oncologic indications.

Photodynamic therapy in dermatology: an update

Topical photodynamic therapy (PDT) is a well‐established treatment modality which has mainly shown to be effective for dermatooncologic conditions like actinic keratoses (AK), Bowens disease, in situ squamous cell carcinoma and superficial basal cell carcinoma (BCC). However, a therapeutical benefit of PDT is also evident for inflammatory dermatoses like localized scleroderma, acne vulgaris and granuloma annulare. Recent work has been focused on the development and evaluation of topical photosensitizers like the heme precursor 5‐aminolevulinic acid (5‐ALA) or its methyl ester (methyl aminolevulinate) inducing photosensitizing porphyrins. These drugs do not induce strong generalized cutaneous photosensitization like the systemically applied porphyrins or their derivatives. For dermatological purposes, incoherent lamps or light‐emitting diode arrays can be used for light activation. Depending on the applied light dose and the concentration of the photosensitizer either cytotoxic effects resulting in tumor destruction or immunomodulatory effects improving the inflammatory conditions occur. Treating superficial oncologic lesions (tumor thickness <2–3 mm) cure rates achieved by PDT are equal to the cure rates of the respective standard therapeutic procedure. The benefits of PDT are the low level of invasiveness and the excellent cosmetic results after treatment.

Photodynamic therapy in dermatology

Currently, topical photodynamic therapy (PDT) has received approval for the treatment of dermato-oncologic conditions like actinic keratoses, Bowens disease, in-situ squamous cell carcinoma and basal cell carcinoma in many countries all over the world. For many non-neoplastic dermatological diseases like localized scleroderma, acne vulgaris and viral warts a therapeutical benefit of PDT is evident, too. Unlike the formerly used, only systemically-applicable haematoporphyrin derivates, the recently developed topical photosensitizers 5-aminolevulinic acid (ALA) or its methyl ester (MAL) induce photosensitizing porphyrins. Moreover, the latter do not induce strong generalized cutaneous photosensitization. Due to the easy accessibility of skin to light activation, incoherent lamps or LED arrays are suitable for PDT. The production of reactive oxygen intermediates like singlet oxygen depends on the applied light dose as well as the concentration and localization of the photosensitizer in the diseased tissue. Either cytotoxic effects resulting in tumor destruction or immunomodulatory effects improving inflammatory skin conditions are induced. Treating superficial non-melanoma skin cancer, PDT has been shown to be highly efficient despite the low level of invasiveness. The excellent cosmetic results after treatment are beneficial, too.

2D luminescence imaging of pH in vivo

Luminescence imaging of biological parameters is an emerging field in biomedical sciences. Tools to study 2D pH distribution are needed to gain new insights into complex disease processes, such as wound healing and tumor metabolism. In recent years, luminescence-based methods for pH measurement have been developed. However, for in vivo applications, especially for studies on humans, biocompatibility and reliability under varying conditions have to be ensured. Here, we present a referenced luminescent sensor for 2D high-resolution imaging of pH in vivo. The ratiometric sensing scheme is based on time-domain luminescence imaging of FITC and ruthenium(II)tris-(4,7-diphenyl-1,10-phenanthroline). To create a biocompatible 2D sensor, these dyes were bound to or incorporated into microparticles (aminocellulose and polyacrylonitrile), and particles were immobilized in polyurethane hydrogel on transparent foils. We show sensor precision and validity by conducting in vitro and in vivo experiments, and we show the versatility in imaging pH during physiological and chronic cutaneous wound healing in humans. Implementation of this technique may open vistas in wound healing, tumor biology, and other biomedical fields.

The impact of the pH value on skin integrity and cutaneous wound healing

The process of cutaneous wound healing comprises three overlapping major phases: inflammation, proliferation and tissue remodelling. However, while mechanisms are studied scientifically on the cellular and subcellular level, there is still a lack of knowledge concerning basic clinical parameters like wound pH or pO2. It could be proven that wound healing is affected by wound pH changes as they can lead to an inhibition of endogenous and therapeutically applied enzymes. Besides, the conformational structure of proteins and their functionality in wound healing is altered. Furthermore, the likelihood of bacterial colonization, which is a common problem in chronic wound pathogenesis, is affected by wound pH alterations. However, wound pH is rarely taken into account in current wound therapy strategies. A routinely performed monitoring of the wound pH and a subsequently adapted wound therapy would most possibly improve chronic wound therapy.

Variable pulsed light is less painful than light-emitting diodes for topical photodynamic therapy of actinic keratosis : a prospective randomized controlled trial

Background  Photodynamic therapy (PDT) of actinic keratosis (AK) using methylaminolaevulinate (MAL) is an effective and safe treatment option, but the procedure is painful.