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Adopting novel sandwich structures with FRP (Fibre Reinforced Polymer) skins and a metallic lattice core, both of which have high specific strength and stiffness, is one way to achieve better mechanical performance while remaining lightweight. Flexural stress is a load pattern that frequently occurs in the structural frame components of automobiles; nonetheless, while the in-plane load scheme has scarcely been examined, the out-of-plane load one has. As a result, the former configuration received consideration in this work. Moreover, short beam specimens were taken into account. The mechanical response of specimens with three different kinds of composite materials as skin material was analysed. The skins were made of CFRP (Carbon Fiber Reinforced Polymer), with two different weaving styles, and AFRP (Aramid Fiber Reinforced Polymer). All-titanium specimens were studied, too. Similar maximum loads and maximum displacement at break were recorded for both CFRP and AFRP specimens, while the all-titanium one resulted stronger. In terms of the load-displacement curves, the first section featured an initial linear phase, followed by a minor load drop, likely attributed to the breakage of fibres. The CFRP specimens showed a sharp fracture of the skin fibres, while for the AFRP, a fraying was observed.

Summary:. Hard-to-heal wounds represent a global and growing medical and economic burden. Skin autografting is a useful treatment option but is often limited by donor site morbidity, logistical considerations, and grafting success in compromised wound beds. Combining autologous skin cell suspension (ASCS) technology with minced dermal grafts can allow for dermal elements and epithelial healing as well as closed donor sites. This study explores the combination of minced autografting with ASCS in healing recalcitrant wounds. Two patients with diabetic foot ulcers (DFUs) whose previous skin grafting had failed were included. Under local anesthesia, donor skin was harvested as a full-thickness ellipse and divided into a superficial split-thickness graft (STSG) and a dermal autograft. ASCS was prepared from the STSG, and the dermal component was finely minced using a scalpel. Prepared wound beds were directly dressed with Telfa clear and compression dressings. Patients included a 62-year-old man with a DFU (15 cm2) on the left plantar heel present for 2 years, and a 53-year-old man with a DFU (10 cm2) on the plantar surface of the first metatarsal head present for 2 years. After combination treatment, complete closure was achieved by days 27 and 24, respectively. There was evidence of continued remodeling and skin thickening for the following 4 months. Combining dermal mincing with ASCS promotes healing of both dermal and epidermal layers while enabling primary closure of donor sites. These initial cases are encouraging, and ongoing studies are validating outcomes in more patients with various hard-to heal wounds.

Humans and other large mammals heal wounds by forming fibrotic scar tissue with diminished function. Here, the authors show that disrupting mechanotransduction through the focal adhesion kinase pathway in large animals accelerates healing, prevents fibrosis, and enhances skin regeneration.

Background:. The advent of acellular dermal matrix (ADM) has revolutionized prosthesis-based breast reconstruction. However, paucity of human cadaveric tissue has resulted in limitation of supply and increased associated costs, prompting concerted effort to identify xenograft alternatives. Although studies have examined the safety of Artia, a porcine-derived ADM, few have evaluated its clinical efficacy as soft tissue reinforcement. This study uniquely evaluates the clinical efficacy of Artia in implant-based breast reconstruction. Methods:. IRB-approved retrospective chart review was conducted to identify 243 consecutive TE-based procedures performed at a tertiary academic medical center between March 2017 and March 2021. Propensity matching was conducted to minimize differences between cohorts. Efficacy metrics, defined as initial tissue expander (TE) fill volume, number of TE fills, and time interval between exchange of TE for final implant, were compared between xenograft (Artia) and allograft (AlloDerm) groups. Results:. Patients who underwent Artia-based breast reconstruction achieved superior initial TE fill volume relative to those who underwent AlloDerm-based breast reconstruction via univariate analysis (317.3 ± 185.8 mL versus 286.1 ± 140.4 mL, P < 0.01) when patient and operative characteristics were well-matched. However, linear regression analysis failed to demonstrate difference in efficacy metrics, such as initial TE fill volume (P = 0.31), ratio between initial TE fill volume and final implant size (P = 0.19), and number of TE fills (P = 0.76). Complication rates were comparable between groups. Conclusion:. This study suggests that Artia can be used as a safe and efficacious alternative to human-derived ADM in immediate TE-based breast reconstruction.

Background: Reporting quality of systematic reviews and meta-analyses is of critical importance in dermatology because of their key role in informing health care decisions. Objective: To assess the compliance of systematic reviews and meta-analyses in leading dermatology journals with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement guidelines. Methods: This review was carried out in accordance with PRISMA guidelines. Included studies were reviews published across 6 years in the top 4 highest-impact-factor dermatology journals of 2017. Records and full texts were screened independently. Data analysis was conducted with univariate multivariable linear regression. The primary outcome was to assess the compliance of systematic reviews and meta-analyses in leading dermatology journals with the PRISMA statement. Results: A total of 166 studies were included and mean PRISMA compliance across all articles was 73%. Compliance significantly improved over time (β = .016; P =

Abstract Fat grafting can reduce radiation‐induced fibrosis. Improved outcomes are found when fat grafts are enriched with adipose‐derived stromal cells (ASCs), implicating ASCs as key drivers of soft tissue regeneration. We have identified a subpopulation of ASCs positive for CD74 with enhanced antifibrotic effects. Compared to CD74− and unsorted (US) ASCs, CD74+ ASCs have increased expression of hepatocyte growth factor, fibroblast growth factor 2, and transforming growth factor β3 (TGF‐β3) and decreased levels of TGF‐β1. Dermal fibroblasts incubated with conditioned media from CD74+ ASCs produced less collagen upon stimulation, compared to fibroblasts incubated with media from CD74− or US ASCs. Upon transplantation, fat grafts enriched with CD74+ ASCs reduced the stiffness, dermal thickness, and collagen content of overlying skin, and decreased the relative proportions of more fibrotic dermal fibroblasts. Improvements in several extracellular matrix components were also appreciated on immunofluorescent staining. Together these findings indicate CD74+ ASCs have antifibrotic qualities and may play an important role in future strategies to address fibrotic remodeling following radiation‐induced fibrosis.

Abstract Fat grafting is a surgical technique able to reconstruct and regenerate soft tissue. The adipose‐derived stromal cells (ASCs) within the stromal vascular fraction are believed to drive these beneficial effects. ASCs are increasingly recognized to be a heterogeneous group, comprised of multiple stem and progenitor subpopulations with distinct functions. We hypothesized the existence of an ASC subpopulation with enhanced angiogenic potential. Human ASCs that were CD34+CD146+, CD34+CD146−, or CD34+ unfractionated (UF) were isolated by flow cytometry for comparison of expression of proangiogenic factors and endothelial tube‐forming potential. Next, lipoaspirate was enriched with either CD34+CD146+, CD34+CD146−, CD34+ UF ASCs, or was not enriched, and grafted beneath the scalp skin of immunodeficient CD‐1 Nude mice (10 000 cells/200 μL/graft). Fat retention was monitored radiographically more than 8 weeks and fat grafts were harvested for histological assessment of quality and vascularization. The CD34+CD146+ subpopulation comprised ~30% of ASCs, and exhibited increased expression of vascular endothelial growth factor and angiopoietin‐1 compared to CD34+CD146− and CD34+ UF ASCs, and increased expression of fibroblast growth factor‐2 compared to CD34+CD146− ASCs. The CD34+CD146+ subpopulation exhibited enhanced induction of tube‐formation compared to CD34+CD146− ASCs. Upon transplantation, fat enriched CD34+CD146+ ASCs underwent less resorption and had improved histologic quality and vascularization. We have identified a subpopulation of CD34+ ASCs with enhanced angiogenic effects in vitro and in vivo, likely mediated by increased expression of potent proangiogenic factors. These findings suggest that enriching lipoaspirate with CD34+CD146+ ASCs may enhance fat graft vascularization and retention in the clinical setting.

Cell therapy for treatment of peripheral arterial disease (PAD) is a promising approach but is limited by poor cell survival when cells are delivered using saline. The objective of this study was to examine the feasibility of aligned nanofibrillar scaffolds as a vehicle for the delivery of human stromal vascular fraction (SVF), and then to assess the efficacy of the cell-seeded scaffolds in a murine model of PAD. Flow cytometric analysis was performed to characterize the phenotype of SVF cells from freshly isolated lipoaspirate, as well as after attachment onto aligned nanofibrillar scaffolds. Flow cytometry results demonstrated that the SVF consisted of 33.1 ± 9.6% CD45+ cells, a small fraction of CD45–/CD31+ (4.5 ± 3.1%) and 45.4 ± 20.0% of CD45–/CD31–/CD34+ cells. Although the subpopulations of SVF did not change significantly after attachment to the aligned nanofibrillar scaffolds, protein secretion of vascular endothelial growth factor (VEGF) significantly increased by six-fold, compared to SVF cultured in suspension. Importantly, when SVF-seeded scaffolds were transplanted into immunodeficient mice with induced hindlimb ischemia, the cell-seeded scaffolds induced a significant higher mean perfusion ratio after 14 days, compared to cells delivered using saline. Together, these results show that aligned nanofibrillar scaffolds promoted cellular attachment, enhanced the secretion of VEGF from attached SVF cells, and their implantation with attached SVF cells stimulated blood perfusion recovery. These findings have important therapeutic implications for the treatment of PAD using SVF.

Summary:. Fibroblasts’ integral role in tissue development, maintenance, and disease represents a fast-growing field of basic science research. Although fibroblasts were long thought to be a homogeneous cell population, recent research has illuminated the unforeseen complexity of these cells, giving rise to the rapidly expanding research field of “fibroblast heterogeneity.” Fibroblasts play a critical role in states of tissue fibrosis such as skin scarring, which affects hundreds of millions of patients annually and causes severe aesthetic, developmental, and functional morbidity. Beyond scarring, major organ fibrosis is an enormous public health concern responsible for nearly half of all deaths in the United States. Because fibrosis is a conserved response to tissue damage in all organs, the study of fibroblasts throughout the body may help us to understand their role in the conditions most relevant to plastic and reconstructive surgery—for instance, skin scarring (eg, from burns, traumatic lacerations, or surgical incisions), “pathological” scarring (hypertrophic scars, keloids), and capsular contracture. Here, we present a basic science review of fibroblast heterogeneity in wound healing, cancer, organ fibrosis, and human dermal architecture. The field of fibroblast heterogeneity is young, and many of the insights discussed have yet to be translated clinically. However, plastic surgeons stand in a unique position to bridge these discoveries into clinical realities. We hope this information can spur readers to consider both what questions in plastic surgery can be studied from the lens of fibroblast heterogeneity, and how these preclinical insights can be translated to improving care of our patients.

Tissue fibrosis is the deposition of excessive extracellular matrix and can occur as part of the body's natural wound healing process upon injury, or as a consequence of diseases such as systemic sclerosis. Skin fibrosis contributes to significant morbidity due to the prevalence of injuries resulting from trauma and burn. Fibroblasts, the principal cells of the dermis, synthesize extracellular matrix to maintain the skin during homeostasis and also play a pivotal role in all stages of wound healing. Although it was previously believed that fibroblasts are homogeneous and mostly quiescent cells, it has become increasingly recognized that numerous fibroblast subtypes with unique functions and morphologies exist. This Review provides an overview of fibroblast heterogeneity in the mammalian dermis. We explain how fibroblast identity relates to their developmental origin, anatomical site and precise location within the skin tissue architecture in both human and mouse dermis. We discuss current evidence for the varied functionality of fibroblasts within the dermis and the relationships between fibroblast subtypes, and explain the current understanding of how fibroblast subpopulations may be controlled through transcriptional regulatory networks and paracrine communications. We consider how fibroblast heterogeneity can influence wound healing and fibrosis, and how insight into fibroblast heterogeneity could lead to novel therapeutic developments and targets for skin fibrosis. Finally, we contemplate how future studies should be shaped to implement knowledge of fibroblast heterogeneity into clinical practice in order to lessen the burden of skin fibrosis.

Background:. Capsular contracture remains a common complication after implant-based breast reconstruction. Previous work has suggested that the use of acellular dermal matrix (ADM) reduces the rate of capsular contracture, though little is understood about the underlying mechanism. As myofibroblasts are believed to be the key cells implicated in contracture formation, we hypothesized that ADM would result in a reduction in periprosthetic myofibroblast concentration. Methods:. Five patients who underwent immediate prepectoral tissue expander placement with anterior ADM coverage and an inferior cuff were included. At the second stage, tissue samples were obtained of both ADM and capsule from each reconstructed breast. Samples were then prepared for hematoxylin and eosin staining and immunohistochemistry for myofibroblast identification (alpha smooth muscle actin and vimentin positive and desmin negative) and analysis. Experimental values are presented as mean ± SD unless otherwise stated. Statistical significance was determined using unpaired t test. Results:. Successful incorporation of ADM was noted in all cases. A significant reduction in myofibroblast concentration was noted in the ADM versus the capsule (P = 0.0018). This was paralleled by significantly thicker periprosthetic capsule formation overlying the formerly raw pectoralis major muscle, that is, not covered by ADM (P < 0.0001). Conclusions:. In the presence of ADM, there are significantly fewer myofibroblasts in breast capsules and thinner capsules on histology. Given the central role of myofibroblasts in the development of clinically significant capsular contracture, this study unmasks a possible mechanism for the protective effect of ADM with respect to capsular contracture development.

Summary:. Radiotherapy (RT) helps cure and palliate thousands of patients with a range of malignant diseases. A major drawback, however, is the collateral damage done to tissues surrounding the tumor in the radiation field. The skin and subcutaneous tissue are among the most severely affected regions. Immediately following RT, the skin may be inflamed, hyperemic, and can form ulcers. With time, the dermis becomes progressively indurated. These acute and chronic changes cause substantial patient morbidity, yet there are few effective treatment modalities able to reduce radiodermatitis. Fat grafting is increasingly recognized as a tool able to reverse the fibrotic skin changes and rejuvenate the irradiated skin. This review outlines the current progress toward describing and understanding the cellular and molecular effects of fat grafting in irradiated skin. Identification of the key factors involved in the pathophysiology of fibrosis following RT will inform therapeutic interventions to enhance its beneficial effects.

Wnt signaling plays a central regulatory role across a remarkably diverse range of functions during embryonic development, including those involved in the formation of bone and cartilage. Wnt signaling continues to play a critical role in adult osteogenic differentiation of mesenchymal stem cells. Disruptions in this highly-conserved and complex system leads to various pathological conditions, including impaired bone healing, autoimmune diseases and malignant degeneration. For reconstructive surgeons, critically sized skeletal defects represent a major challenge. These are frequently associated with significant morbidity in both the recipient and donor sites. The Wnt pathway is an attractive therapeutic target with the potential to directly modulate stem cells responsible for skeletal tissue regeneration and promote bone growth, suggesting that Wnt factors could be used to promote bone healing after trauma. This review summarizes our current understanding of the essential role of the Wnt pathway in bone regeneration and repair.

Background:. Incidentalomas are lesions found coincidentally during examination, imaging, or surgical procedures. Preoperative computed tomography angiography (CTA) before abdominal flap harvest for breast reconstruction can lead to identification of incidentalomas leading to the need for further investigations. The aim of this study was to examine the prevalence of incidental findings on preoperative CTA and to determine their impact on management. Methods:. A retrospective chart review was performed at a single tertiary institution. CTA reports were analyzed for the presence of incidental findings and details of follow-up were studied. Logistic regression was used to identify factors associated with incidental findings. Results:. One hundred eighteen patients with a mean age of 49 years were included in the study. The majority of patients underwent bilateral reconstruction (65%, n = 77) in the immediate setting (70%, n = 83). Fifty-six percentage had an incidental finding on CTA, with hepatic (20%), renal (14%), and osseous (11%) abnormalities being most common. Additional imaging including ultrasound, CT, and magnetic resonance imaging were recommended in 19 cases (16%). Additional consultations were sought for 3 patients before reconstruction (with suspicion of bone metastases, an intraabdominal mass, and suspicion of colonic malignancy, respectively). No significant surgical delay secondary to CT findings was noted. Conclusions:. Incidentalomas following preoperative CTA of the abdomen/pelvis are common (56%). However, unlike previous reports, we did not observe a change in reconstructive plan following incidentaloma discovery. We recommend that all patients are counseled pre-CTA regarding the possibilities of incidentaloma detection and need for additional imaging.

Background:. Fingertip amputations are common. This study reports on the outcomes of composite grafts used for fingertip amputations in children, measuring graft take, predictors of graft take, complications, and patient-reported outcomes. Methods:. A retrospective case series of consecutive patients (≤ 16 years) undergoing composite grafts for fingertip amputations in a tertiary pediatric hospital, January 06 to December 16, was performed. Information was collected on amputations, graft take, and complications. Logistic regression was used to analyze factors predicting graft take (partial/complete or failure) including age; amputation level; mechanism and time delay to surgery. Patients were contacted via post or telephone to ask about functional and cosmetic outcomes and their perception of graft take. Results:. One hundred patients [57 (57%) males; mean age, 4.41 ± 3.98 years], presenting with 100 fingertip amputations, met the inclusion criteria. Amputation mechanism was crush in 75 (75%), avulsion in 13 (13%), and laceration in 12 (13%). Thirteen (13%) composite grafts survived completely, 46 (46%) partially, and 41 (41%) failed. Graft survival was higher in children under 4 years (P = 0.016). Seventeen (17%) grafts became infected, 9 (9%) required a reoperation, 9 (9%) had wound healing complications, and 4 (4%) patients developed psychological complications. Patient-reported survival was 33% higher than medical-reported survival. Cosmetic issues were the commonest complication reported by patients. Patients rated fingertips looking 3.5/5 normal, and that they were 4/5 satisfied with the appearance. Most patients were using their fingers normally by 2–6 months. Conclusions:. Composite grafts for fingertip amputations mostly only partially survive, but morbidity is low, patient satisfaction is high, and acceptable cosmetic and functional outcomes are achieved.