a-full-skin-defect-model-to-evaluate-vascularization-biomaterials

A Full Skin Defect Model to Evaluate Vascularization of Biomaterials <em>In Vivo</em>

Insufficient vascularization is considered to be one of the main factors limiting the clinical success of tissue-engineered constructs. In order to ...

ischemic-tissue-injury-dorsal-skinfold-chamber-mouse-skin-flap-model

Ischemic Tissue Injury in the Dorsal Skinfold Chamber of the Mouse: A Skin Flap Model to Investigate Acute Persistent Ischemia

Despite profound expertise and advanced surgical techniques, ischemia-induced complications ranging from wound breakdown to extensive tissue necrosis are ...

University Hospital Zürich

University Hospital Zurich

The objective of this study was to analyze whether erythropoietin (EPO) protects from necrosis of critically perfused musculocutaneous tissue and the mechanisms by which this protection is achieved.

Erythropoietin protects critically perfused flap tissue.

Recent findings have attested the protective effects of erythropoietin (EPO) in ischemically challenged organs. We therefore aimed at elaborating the underlying mechanism of EPO-mediated protection in musculocutaneous tissue undergoing persistent ischemia after acute injury. Mice were assigned to five experimental groups equipped with a randomly perfused flap fixed in a dorsal skinfold chamber, whereas the sixth group did not undergo flap preparation: EPO, L-Name, EPO and L-Name, EPO and bevacizumab, untreated flap, and nonischemic chamber (control). Intravital fluorescence microscopic analysis of microhemodynamics, apoptotic cell death, macromolecular leakage and angiogenesis was carried out over a 10-day period. Further, immunohistochemical analysis was used to study the protein expression of endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF). Increased expression of eNOS in EPO-administered mice correlated with significant arteriolar dilation and thus increased blood flow resulting in a maintained functional capillary density (FCD) at day 10. In addition, EPO induced a VEGF upregulation, which was associated with newly formed capillaries. In addition, EPO was able to reduce ischemia-induced apoptotic cell death and finally to significantly reduce flap necrosis. In contrast, coadministration of L-Name abolished EPO-mediated tissue protection by abrogating the dilatory effect resulting in reduced FCD and tissue survival, without counteracting angiogenesis and apoptotic cell death, whereas additional administration of bevacizumab did not influence the beneficial effect of EPO on flap survival despite abrogating angiogenesis. Macromolecular leakage was found to be increased in all treatment groups. This study shows that EPO administration prevents musculocutaneous tissue from ischemic necrosis as a consequence of an eNOS-dependent arteriolar hyperperfusion maintaining capillary perfusion, thus representing a promising approach to pharmacologically protect ischemically challenged tissue.

Erythropoietin-induced upregulation of endothelial nitric oxide synthase but not vascular endothelial growth factor prevents musculocutaneous tissue from ischemic damage.

Vital tissue provided by fresh frozen tissue banking is often required for genetic tumor profiling and tailored therapies. However, the potential patient benefits of fresh frozen tissue banking are currently limited to university hospitals. The objective of the present pilot study--the first one in the literature--was to evaluate whether fresh frozen tissue banking is feasible in a regional hospital without an integrated institute of pathology.

Tissue banking in a regional hospital: a promising future concept? First report on fresh frozen tissue banking in a hospital without an integrated institute of pathology.

To investigate whether systemic erythropoietin administration can prevent secondary burn progression in an experimental model and to elucidate the underlying mechanisms.

Secondary burn progression decreased by erythropoietin.

Recent findings have attested to EPO tissue-protective effects in ischemically challenged tissues. Therefore, the study aimed at elaborating the effect of systemic pre- and postconditioning using EPO in a mouse model of persistent ischemia of the skin.

Long-term preconditioning with erythropoietin reduces ischemia-induced skin necrosis.

Shockwave (SW) application has been shown to limit flap necrosis. However, the underlying microhemodynamic mechanisms remain unclear. Therefore, the objective of this study was to analyze the effect of SW application on a microcirculatory level.

Local shockwave-induced capillary recruitment improves survival of musculocutaneous flaps.

Delayed wound healing and scar formation are among the most frequent complications after surgical interventions. Although biodegradable surgical sutures present an excellent drug delivery opportunity, their primary function is tissue fixation. Mesenchymal stem cells (MSC) act as trophic mediators and are successful in activating biomaterials. Here biodegradable sutures were filled with adipose-derived mesenchymal stem cells (ASC) to provide a pro-regenerative environment at the injured site. Results showed that after filling, ASCs attach to the suture material, distribute equally throughout the filaments, and remain viable in the suture. Among a broad panel of cytokines, cell-filled sutures constantly release vascular endothelial growth factor to supernatants. Such conditioned media was evaluated in an in vitro wound healing assay and showed a significant decrease in the open wound area compared to controls. After suturing in an ex vivo wound model, cells remained in the suture and maintained their metabolic activity. Furthermore, cell-filled sutures can be cryopreserved without losing their viability. This study presents an innovative approach to equip surgical sutures with pro-regenerative features and allows the treatment and fixation of wounds in one step, therefore representing a promising tool to promote wound healing after injury.

Surgical sutures filled with adipose-derived stem cells promote wound healing.

The sentinel lymph node (SLN) procedure for colon cancer patients has been increasingly performed over the past decade and has shown advantages regarding lymph node staging. However, there are concerns that the manipulation of the colon, particularly the blue dye injection, results in isolated tumor cell dissemination to lymph nodes. Therefore, the objective of the present study was to evaluate whether the blue dye injection during the SLN procedure for colon cancer induces epithelial cell dissemination to the regional lymph nodes using a fake SLN procedure as a model.

Blue dye injection does not induce dissemination of epithelial cells during SLN procedure in colon cancer patients.

After a burn injury, superficial partial-thickness burn wounds may progress to deep partial-thickness or full-thickness burn wounds, if kept untreated. This phenomenon is called secondary burn wound progression or conversion. Burn wound depth is an important determinant of patient morbidity and mortality. Therefore, reduction or even the prevention of secondary burn wound progression is one goal of the acute care of burned patients. The objective of this study was to review preclinical approaches evaluating therapies to reduce burn wound progression. A systematic review of experimental approaches in animals that aim at reducing or preventing secondary burn wound progression was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta Analysis (PRISMA) guidelines. The selected references consist of all the peer-reviewed studies performed in vivo in animals and review articles published in English, German, Italian, Spanish, or French language relevant to the topic of secondary burn wound progression. We searched MEDLINE, Cochrane Library, and Google Scholar including all the articles published from the beginning of notations to the present. The search was conducted between May 3, 2012 and December 26, 2013. We included 29 experimental studies in this review, investigating agents that maintain or increase local perfusion conditions, as well as the agents that exhibit an anti-coagulatory, an anti-inflammatory, or an anti-apoptotic property. Warm water, simvastatin, EPO, or cerium nitrate may represent particularly promising approaches for the translation into clinical use in the near future. This review demonstrates promising experimental approaches that might reduce secondary burn wound progression. Nevertheless, a translation into clinical application needs to confirm the results compiled in experimental animal studies.

ArticleTotal : 2	Year
Publication title Cited by 13	2014
Publication title Cited by 15	2014

Article	Year
Erythropoietin protects critically perfused flap tissue. Annals of surgery\| PubMed ID: 19092336	2008
Erythropoietin-induced upregulation of endothelial nitric oxide synthase but not vascular endothelial growth factor prevents musculocutaneous tissue from ischemic damage. Laboratory investigation; a journal of technical methods and pathology\| PubMed ID: 19901910	2010
Tissue banking in a regional hospital: a promising future concept? First report on fresh frozen tissue banking in a hospital without an integrated institute of pathology. World journal of surgery\| PubMed ID: 22638684	2012
Secondary burn progression decreased by erythropoietin. Critical care medicine\| PubMed ID: 23324953	2013
Long-term preconditioning with erythropoietin reduces ischemia-induced skin necrosis. Microcirculation (New York, N.Y. : 1994)\| PubMed ID: 23510335	2013
Local shockwave-induced capillary recruitment improves survival of musculocutaneous flaps. The Journal of surgical research\| PubMed ID: 23582757	2013
Surgical sutures filled with adipose-derived stem cells promote wound healing. PloS one\| PubMed ID: 24625821	2014
Blue dye injection does not induce dissemination of epithelial cells during SLN procedure in colon cancer patients. International journal of colorectal disease\| PubMed ID: 24763756	2014
Treatment of Secondary Burn Wound Progression in Contact Burns-A Systematic Review of Experimental Approaches. Journal of burn care & research : official publication of the American Burn Association\| PubMed ID: 25094011	2014

Farid Rezaeian

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