The Crucial Role of Vascularization and Lymphangiogenesis in Skin Reconstruction

2018 ◽  
Vol 59 (3-4) ◽  
pp. 242-254 ◽  
Author(s):  
Florian S.  Frueh ◽  
Nadia Sanchez-Macedo ◽  
Maurizio Calcagni ◽  
Pietro Giovanoli ◽  
Nicole Lindenblatt

Background: The treatment of extensive skin defects and bradytrophic wounds remains a challenge in clinical practice. Despite emerging tissue engineering approaches, skin grafts and dermal substitutes are still the routine procedure for the majority of skin defects. Here, we review the role of vascularization and lymphangiogenesis for skin grafting and dermal substitutes from the clinician’s perspective. Summary: Graft revascularization is a dynamic combination of inosculation, angiogenesis, and vasculogenesis. The majority of a graft’s microvasculature regresses and is replaced by ingrowing microvessels from the wound bed, finally resulting in a chimeric microvascular network. After inosculation within 48–72 h, the graft is re-oxygenated. In contrast to skin grafts, the vascularization of dermal substitutes is slow and dependent on the ingrowth of vessel-forming angiogenic cells. Preclinical angiogenic strategies with adipose tissue-derived isolates are appealing for the treatment of difficult wounds and may markedly accelerate skin reconstruction in the future. However, their translation from bench to bedside is still restricted by major regulatory restrictions. Finally, the lymphatic system contributes to edema reduction and the removal of local wound debris. Therapeutic lymphangiogenesis is an emerging field of research in skin reconstruction. Key Messages: For the successful engraftment of skin grafts and dermal substitutes, the rapid formation of a microvascular network is of pivotal importance. Hence, to understand the biological processes behind revascularization of skin substitutes and to implement this knowledge into clinical practice is a prerequisite when treating skin defects. Furthermore, a functional lymphatic drainage crucially contributes to the engraftment of skin substitutes.

Author(s):  
Stephen M. Milner

Skin grafting is an indispensable technique used in a variety of clinical situations, including acute burns, traumatic wounds, scar contracture release, and oncological and congenital deficiencies. The author’s preferred techniques for harvesting and resurfacing various skin defects using split- and full-thickness skin grafts are described in this chapter, together with the assessment of donor and recipient sites, preoperative preparation and postoperative considerations.


2020 ◽  
Vol 41 (Supplement_1) ◽  
pp. S167-S168
Author(s):  
Laura Cooper ◽  
Phillip Kemp Bohan ◽  
Anders H Carlsson ◽  
Rodney K Chan ◽  
Tyler Everett

Abstract Introduction Skin graft survival relies on imbibition, inosculation, and revascularization from the wound bed. When a wound bed is poorly vascularized, as in the case of exposed fascia, tendon or bone, skin grafting may be delayed until the wound bed improves. We propose that topical nutrient supplementation may be able to increase take of skin grafts applied over an avascular wound bed. Methods Twenty full-thickness 5cm-diameter wounds were created on the dorsum of anesthetized swine and a dermal substitute (0.4mm, 0.8mm, 1.2mm, or 1.6mm thick) was placed on each wound. Negative pressure therapy with and without intermittent (3x per day) saline instillation was applied. Wounds were analyzed using a non-contact 3D camera at day 7 and day 14. Results Dermal substitutes of 0.8mm, 1.2mm, and 1.6mm thicknesses inhibited graft take significantly (p< 0.01, p=0.02, p< 0.01, respectively) for all wounds treated with wound vac alone. Addition of the normal saline instill showed a significant improvement in graft take (p=0.03) over wound vac alone for the wounds treated with the 0.8mm dermal substitute. Wounds covered with 1.2mm and 1.6mm dermal substitute continued to show significantly decreased graft take (p=0.03 and p=0.02, respectively). Wounds with 0.4mm dermal substitute showed similar graft take to control for both the wound vac and wound vac + instill treatments. Conclusions Dermal substitutes ≥0.8mm create a successful model of an avascular wound bed. Vac + instill treatment overcame the impedance of an avascular wound bed only for the 0.8mm dermal substitute thickness. This thickness of dermal substitute creates an ideal avascular wound bed model from which to conduct further studies incorporating topical nutrients instilled directly onto skin grafts placed onto avascular wound beds. Applicability of Research to Practice Single-stage skin grafting procedures onto avascular wound beds may become feasible with topical nutrient supplementation providing the environment to maintain graft survival until the wound bed is able to support the skin graft.


Author(s):  
K. Preethi ◽  
V. Gireesh Kumar ◽  
K.B. P. Raghavender ◽  
D. Pramod Kumar

The objective of this study was to reconstruct the skin defects with partial thickness mesh skin grafts and to compare the efficacy of platelet rich plasma along with skin grafting. The present study was performed on ten dogs with twelve wounds which were unamenable to primary closure. All the wounds were reconstructed with partial thickness mesh skin grafting technique in which six wounds were assigned to group–I and remaining were similarly reconstructed followed by injection of platelet rich plasma were assigned to group-II. It was concluded from the present study that, partial thickness mesh skin grafting procedure showed good results for correction of skin defects. The group II wounds showed early primary healing with no difference in graft viability.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2317-2317
Author(s):  
Hong Xu ◽  
Yiming Huang ◽  
Lala-Rukh Hussain ◽  
Suzanne T Ildstad

Abstract There is an increased rate of graft failure associated with nonmyeloablative conditioning approaches for hematopoietic stem cell (HSC) transplantation, often resulting in subsequent sensitization to donor alloantigens. Recipient sensitization is among the most critical of problems currently facing clinical transplantation, resulting in hyperacute rejection of transplanted HSC and/or organ grafts by existing donor-specific antibodies (Ab) against major histocompatibility (MHC) antigens in secondary transplants. The humoral immune response to minor histocompatibility antigens (Mi-HAg) has not been fully evaluated in BMC transplantation to date. In this study, we explored the role of allosensitization to Mi-HAg in BMC transplant rejection using a mouse model. AKR (H-2k) mice were sensitized with donor skin grafts from MHC-matched, but minor antigen-disparate B10.BR (H-2k) mice. Significantly higher levels of Abs against donor were generated as detected at 4 weeks after skin grafting by flow cytometry cross match assay (mean fluorescence intensity (MFI) 231.3 ± 151.1; P < 0.0001) compared with the Ab levels in sera of naïve AKR mice (MFI 4.2 ± 2.0) . The MFI of Ab titer to anti-Mi-HAg was similar to that in mice after rejecting skin grafts with MHC disparity (MFI: 231.3 ± 139.0) or MHC plus Mi-HAg disparity (MFI: 301.1 ± 141.1). IgG subclasses of IgG1, IgG2a, and IgG2b were detected in all tested AKR mice with high levels of anti–donor total IgG. Surprisingly, the Abs generated to minor antigens were not donor-specific as they also bound to splenocytes from B6 (H-2b), BALB/c (H-2d), C3H (H-2k) and B10.D2 (H-2d) mice. In subsequent HSC transplantation performed 5–7 weeks after skin grafting, only 20% of B10.BR skin sensitized AKR mice engrafted after ablative conditioning. In contrast, all naïve AKR control mice engrafted but none did in mice sensitized to MHC alloantigens. These findings correlated with in vivo cytotoxicity assays performed at the same time point. Mi-HAg sensitized AKR mice eliminated CFSE labeled donor splenocytes with a significantly faster rate than naïve AKR but significantly slower rate than the mice sensitized to MHC alloantigen. We previously reported that blockade of signaling via the CD40/CD154 co-stimulatory pathway with anti-CD154 induces B cell tolerance and abrogates donor-specific Ab generation in a MHC plus minor antigen mismatched mouse model. Here, we therefore examined whether CD154 blockade during exposure to minor antigens would also prevent sensitization to minor antigens. The production of anti-donor-Mi-HAg antibodies was totally prevented in mice treated with anti-CD154 mAb (MFI 6.1±3.48l P=0.33) compared with the Ab in naïve mice (3.9±0.25), suggesting a dominant role of the CD154:CD40 pathway in B-cell responses to Mi-HAg. Moreover, anti-CD154 treatment promoted bone marrow engraftment to 100% in recipients previously exposed to donor Mi-HAg, suggesting that antibody and not T cells play a dominant role in sensitization to minor antigens. These data demonstrate that sensitization to minor antigens poses a significant barrier in transplantation, but with less intensity than sensitization to MHC antigens, and can be prevented by anti-CD154 mAb. Our findings may identify a novel and clinically relevant approach in the development of conditioning approaches to enhance engraftment but prevent sensitization in the event of graft failure.


2020 ◽  
Vol 08 (01) ◽  
pp. e77-e80
Author(s):  
Lin Qiu ◽  
Xuan Zhang ◽  
Yan Liu ◽  
Yuexian Fu ◽  
Xingang Yuan

AbstractPediatric penile skin grafting is rarely performed. We present a case series of four pediatric patients receiving skin grafting due to the loss of penile skin. The four boys were followed up for 1 to 5 years. One full-thickness skin graft and three split-thickness skin grafts (STSGs) survived well with low Vancouver scar scale scores. One boy gradually developed lymphedema of the distal foreskin and underwent a second preputioplasty. He presented with normal erectile function and did not experience any pain. We propose thick STSGs as the most appropriate choice for pediatric penile skin reconstruction. Lymphedema of the foreskin is an important long-term complication of penile skin grafting.


2020 ◽  
Vol 48 (5) ◽  
pp. 2295-2305
Author(s):  
Jiawei Zhang ◽  
Dandan Li ◽  
Rui Zhang ◽  
Peng Gao ◽  
Rongxue Peng ◽  
...  

The role of miR-21 in the pathogenesis of various liver diseases, together with the possibility of detecting microRNA in the circulation, makes miR-21 a potential biomarker for noninvasive detection. In this review, we summarize the potential utility of extracellular miR-21 in the clinical management of hepatic disease patients and compared it with the current clinical practice. MiR-21 shows screening and prognostic value for liver cancer. In liver cirrhosis, miR-21 may serve as a biomarker for the differentiating diagnosis and prognosis. MiR-21 is also a potential biomarker for the severity of hepatitis. We elucidate the disease condition under which miR-21 testing can reach the expected performance. Though miR-21 is a key regulator of liver diseases, microRNAs coordinate with each other in the complex regulatory network. As a result, the performance of miR-21 is better when combined with other microRNAs or classical biomarkers under certain clinical circumstances.


1994 ◽  
Vol 49 (1) ◽  
pp. 30-33 ◽  
Author(s):  
J. Jarrett Clinton ◽  
Kathleen McCormick ◽  
Jacqueline Besteman

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