Transient non‐viral cutaneous gene delivery in burn wounds

Steinstraesser, Lars; Hirsch, Tobias; Beller, J. J.; Mittler, D.; Sorkin, Michael; Pazdierny, G.; Jacobsen, Frank; Eriksson, Elof; Steinau, Hans Ulrich

doi:10.1002/jgm.1099

Cited by 14 publications

(7 citation statements)

References 36 publications

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“…However, in vivo studies of a mouse intraperitoneal fat model showed that only the use of naked, plasmid DNA–containing scaffolds yielded successful long-term transgene delivery, which was determined by higher expression levels of both luciferase and green fluorescent protein. Several other groups (138–141) have also reported this contradiction between in vitro and in vivo results, which may be due to the interactions among carriers, host tissue, and immunity that cannot be adequately replicated in an in vitro setting. In addition to the delivery of nonviral vectors, POC has been investigated for use as a substrate to deliver genes via a lentivirus.…”

Section: Applications In Regenerative Engineeringmentioning

confidence: 97%

Citrate-Based Biomaterials and Their Applications in Regenerative Engineering

Tran

Yang

Ameer

2015

Annu. Rev. Mater. Res.

111

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Advances in biomaterials science and engineering are crucial to translating regenerative engineering, an emerging field that aims to recreate complex tissues, into clinical practice. In this regard, citrate-based biomaterials have become an important tool owing to their versatile material and biological characteristics including unique antioxidant, antimicrobial, adhesive, and fluorescent properties. This review discusses fundamental design considerations, strategies to incorporate unique functionality, and examples of how citrate-based biomaterials can be an enabling technology for regenerative engineering.

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Section: Applications In Regenerative Engineeringmentioning

confidence: 97%

Citrate-Based Biomaterials and Their Applications in Regenerative Engineering

Tran

Yang

Ameer

2015

Annu. Rev. Mater. Res.

111

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“…Studies investigating skin disorders in humans are limited owing to ethical concerns, leading to dependence on in vitro and experimental animal models to investigate novel therapies and biologic and pathophysiologic pathways [3]. Many models have been developed [7], but in vitro and in vivo models may show poor consistency with clinical situations [27]. …”

Section: Introductionmentioning

confidence: 99%

“…Interspecies differences in anatomy and physiology, differences in cause and course between natural human disease and artificially induced nonhuman pathology, and stress experienced by animals in laboratories invariably alter research results. Few in vitro or nonmammalian surrogate experiments accurately or adequately duplicate, or recapitulate, the full physiology of the human model for wound healing purposes [27]. Many research efforts seek new innovative approaches to in vitro modeling of in vivo complexity without clear progress or improved relevance.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, this approach offers improved translation between the investigative laboratory and the clinical setting. Skin infection and wound healing studies in skin explants have been performed previously [16, 27], and in most cases, epithelialization was analyzed [26]. In addition, the change in tensile strength can be monitored in the experimental setting [8].…”

Section: Introductionmentioning

confidence: 99%

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A novel human skin chamber model to study wound infection ex vivo

et al. 2009

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Wound infections with multi-drug resistant bacteria increase morbidity and mortality and have considerable socioeconomic impact. They can lead to impaired wound healing, resulting in rising treatment costs. The aim of this study was to investigate an ex vivo human wound infection model. Human full-thickness skin from the operating room (OR) was placed into the Bo-Drum® and cultivated for 7 days in an air–liquid interphase. On day 8, the skin was inoculated with either (1) Pseudomonas aeruginosa, (2) Staphylococcus aureus (105 CFU, n = 3) or (3) carrier control. 1, 3 and 7 days after inoculation colony forming units in the tissue/media were determined and cytokine expression was quantified. A reliable and reproducible wound infection could be established for 7 days. At this timepoint, 1.8 × 108 CFU/g tissue of P. aeruginosa and 2 × 107 CFU/g tissue of S. aureus were detected. Immunohistochemical analysis demonstrated bacterial infection and epidermolysis in infected skin. RT-PCR analysis exhibited a significant induction of proinflammatory cytokines after infection. The BO-drum® is a robust, easy-to-use, sterilizable and reusable ex vivo full-skin culture system. For investigation of wound infection, treatment and healing, the BO-drum® presents a convenient model and may help to standardize wound research.

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“…1,16 However, very few in vitro models can completely reproduce the physiology of human skin for wound repair studies. 17 Lack of multidimensional growth makes the mono-layer keratinocyte culture a less robust tool for wound healing investigation. Despite the fact that both keratinocyte-fibroblast co-culture and organotypic culture have the characters of three-dimensional cell culture, their fidelity to in vivo is still limited.…”

mentioning

confidence: 99%

Application of a partial-thickness human ex vivo skin culture model in cutaneous wound healing study

Hong

Song

et al. 2012

Laboratory Investigation

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A number of in vivo and ex vivo skin models have been applied to human wound healing studies. A reliable skin model, which recapitulates the features of human wound repair, is essential for the clinical and mechanical investigation of human cutaneous wound healing. Full-skin ex vivo culture systems have been used in wound healing studies. However, important structures of the skin, such as the differentiation of keratinocytes and epidermis-dermis junction, are poorly characterized in this model. This study aims to develop an optimized partial-thickness human ex vivo skin culture (HESC) model to maintain human skin characteristics in vitro. During our culture, the basal layer, suprabasal layer, and stratum granulosum layer of epidermis were preserved until day 8. Analyses of hemidesmosome proteins, bullous pemphigoid antigen 1 (BP180) and 2 (BP230), showed that the integrity of the basement membrane of the epidermis was well preserved in the HESC model. In contrast, an organotypic culture with human keratinocytes and fibroblasts failed to show an integrated basement membrane. Maintenance of skin structure by histological analysis and proliferation of epidermal keratinocytes by Ki67 staining were observed in our model for 12 days. Complete re-epithelialization of the wounding area was observed at day 6 post wounding when a superficial incisional wound was created. The expression of Ki-67 and keratin 6, indicators of activated keratinocytes in epidermis, was significantly upregulated and new collagen synthesis was found in the dermis during the wound healing process. As control, we also used organotypic culture in studying the differentiation of the keratinocyte layers and incisional wound repair. It turned out that our model has advantage in these study fields. The results suggest that our HESC model retains important elements of in vivo skin and has significant advantages for the wound healing studies in vitro.Laboratory Investigation (2012) 92, 584-599; doi:10.1038/labinvest.2011.184; published online 9 January 2012 KEYWORDS: collagen reproduction; human skin ex vivo culture; keratinocyte apoptosis; keratinocyte proliferation; keratinocyte differentiation; keratinocyte migration; wound healing Wound closure is a complex process involving multiple factors in several dynamic phases. A successful experimental model will encapsulate each phase to better understand the mechanistic features of wound repair and to the development of biological therapeutics for clinical use.1 Currently, popular wound healing models can be classified as in vivo or in vitro with model selection dependent on the objectives and hypotheses of the investigation. An in vivo model utilizing animal subjects has the advantages of simulating wound healing that is most similar to clinical cases. For example, the host's vascular and immune systems, as well as the external environment, influence animal models like humans. Although mouse, 2 rat, 3 rabbit, 4 and guinea pig 5 wound healing models are used to imitate human skin repair, these models are af...

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Transient non‐viral cutaneous gene delivery in burn wounds

Cited by 14 publications

References 36 publications

Citrate-Based Biomaterials and Their Applications in Regenerative Engineering

Citrate-Based Biomaterials and Their Applications in Regenerative Engineering

A novel human skin chamber model to study wound infection ex vivo

Application of a partial-thickness human ex vivo skin culture model in cutaneous wound healing study

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