Comparison of the Effect of Platelet-rich Plasma (PRP) and Fat Graft on Autologous Bone Grafting in a Randomized-controlled Experimental Skull Model.

Gold standard method for the treatment of critical-sized bone defects is the autogenous bone grafting procedure. A number of new and potentially useful adjuncts currently are being investigated to enhance the success of bone grafting. We propose to evaluate the effect of the most known and easily obtained 2 biological materials, fat graft and platelet-rich plasma (PRP), on bone graft healing. Twenty-seven New Zealand male rabbits were included in this randomized, controlled study. Two-sided 15-mm diameter bone defects were created in the parietal bones and the bones taken were replaced right-to-left and vice versa with 1 control group, 1 fat graft applied group, and the last one PRP applied group. Histologic evaluation and 3-dimensional maxillofacial computerized tomography were performed and bone density was calculated. In radiologic analysis, bone density was significantly different in the PRP group compared with the control and fat graft group in the 12th week (P<0.05). In histologic scoring analysis, the PRP group had a better score than the control and fat graft group, while the fat graft group was worse than the control group in the 6th week (P<0.05). The addition of PRP had a positive effect whereas fat graft had a negative effect on bone graft healing compared with the control group.

Topical Tacrolimus and Mycophenolic Acid Therapy Synergizes with Low Dose Systemic Immunosuppression to Sustain Vascularized Composite Allograft Survival.

AIM: The goal of this study was to evaluate whether topical administration of tacrolimus (TAC) and mycophenolic acid (MPA) at the transplant site enables vascularized composite allograft (VCA) survival with significant minimization of the dose and adverse effects of systemic TAC (STAC) immunosuppression. MATERIALS AND METHODS: Lewis (Lew) rats received orthotopic hind limb allotransplants from fully mismatched Brown Norway (BN) donors. Group 1 (Controls) received no treatment. Other groups were treated with STAC at a dose of 1 mg/kg/day for 7 days. On post-operative day (POD) 8, the STAC dose was dropped to 0.1 mg/kg/day for Group 2 and maintained at 1 mg/kg for Group 3. Group 4 received topical application of TAC and MPA on the transplanted (Tx) limb starting POD 8 without STAC. Group 5 received topical TAC and MPA on the contralateral non-Tx limb and Group 6 received topical TAC and MPA on the Tx limb starting POD 8 along with low dose STAC (0.1 mg/kg/day). Treatment was continued until the study end point was reached, defined as either grade 3 rejection or allograft survival exceeding 100 days. .We conducted sequential LC-MS/MS measurements to assess TAC and MPA concentrations in both blood/plasma and allograft tissues. Additionally, we evaluated markers indicative of organ toxicity associated with STAC immunosuppression. RESULTS: Compared to controls, topical therapy with TAC+MPA significantly prolonged allograft survival beyond 100 daysat very low dose STAC (0.1 mg/kg/day) (Group 6). The histopathological assessment of the grafts was consistent with the clinical outcomes. .Drug levels in blood/plasma remained low or undetectable, while allograft tissues showed higher drug concentrations compared to contralateral limb tissues (P<0.05). . Urinary creatinine clearance remained within the normal range at 2.5 mL/min. CONCLUSION: Combination therapy with topical TAC and MPA synergizes with a very low dose, corticosteroid- free-STAC regimen and facilitates rejection-free, prolonged VCA survival without morbidity.

Effectiveness of early rehabilitation in hand burns.

BACKGROUND: Hand burn trauma occurs quite commonly and the outcome of hand burns can significantly impact self-care daily function, work and employment, leisure activities, and overall health-related quality of life. The overall goal of the management of hand burn trauma is to optimize hand function. Rehabilitation and restoration of hand function are critical for the patient's independence and re-integration into society and work. The purpose of this study is to present our experience with 105 hand burn trauma patients admitted and treated in our burn center and to show the efficacy of early rehabilitation on their ability to return to their prior social life and work. METHODS: In our study, we included that 105 patients with acute severe hand burn trauma were hospitalized in Gulhane burn center between 2017 and 2021. They underwent rehabilitation program daily sessions. Patients with hand burns are evaluated by ranges of motions (ROM), grip strength, Cochin Hand Function Scale (CHFS), and Michigan Hand Questionnaire (MHQ) 12 months after the injury. RESULTS: Overall, mean digital total active motion were >180°. The mean values for grip strength of dominant hand for men were 27.2±9.3 kg, for women were 22.0±8.8 kg and non-dominant hand for men were 24.05±13.8 kg, for women were 17.8±10.3 kg. Total score of 5 items was 19.0 in CHFS. The mean overall score on the MHQ was 62.3±27.4. All obtained data were within normal or accepted functional ranges. Spearman correlation coefficient indicates a negative correlation between MHQ and CHFS (p≤0.01). CONCLUSION: A comprehensive rehabilitation program is essential in helping patients to regain optimal function after hand burn trauma. Physiotherapy and occupational therapy is most beneficial when started at the time of admission.

Tacrolimus-Eluting Disk within the Allograft Enables Vascularized Composite Allograft Survival with Site-Specific Immunosuppression without Systemic Toxicity.

AIM: Widespread clinical application of vascularized composite allotransplantation (VCA) has been limited by the need for lifelong systemic immunosuppression to prevent rejection. Our goal was to develop a site-specific immunosuppressive strategy that promotes VCA allograft survival and minimizes the risk of systemic side effects. METHODS: Tacrolimus loaded polycaprolactone (TAC-PCL) disks were prepared and tested for their efficacy in sustaining VCA allograft survival via site-specific immunosuppression. Brown Norway-to-Lewis rat hind limb transplantations were performed; animals received one TAC disk either in the transplanted (DTx) or in the contralateral non-transplanted (DnonTx) limbs. In another group, animals received DTx and lymphadenectomy on Tx side. Blood and allograft levels of TAC were measured using LC-MS/MS. Systemic toxicity was evaluated. RESULTS: Animals that received DTx achieved long-term allograft survival (> 200 days) without signs of metabolic and infectious complications. In these animals, TAC blood levels were low but stable between 2 to 5 ng/mL for nearly 100 days. High concentrations of TAC were achieved in the allografts and the draining lymph nodes (DLN). Animals that underwent lymphadenectomy rejected their allograft by 175 days. Animals that received DnonTx rejected their allografts by day 70. CONCLUSION: Controlled delivery of TAC directly within the allograft (with a single TAC disk) effectively inhibits rejection and prolongs VCA allograft survival, while mitigating the complications of systemic immunosuppression. There was a survival benefit of delivering TAC within the allograft as compared to a remote site. We believe this approach of local drug delivery has significant implications for drug administration in transplantation.

Loop nerve graft prefabrication for peripheral nerve defect reconstruction.

BACKGROUND: Delayed autologous nerve graft reconstruction is inevitable in devastating injuries. Delayed or prolonged repair time has deleterious effects on nerve grafts. We aimed improving and accelerating nerve graft reconstruction process in a rat long nerve defect model with loop nerve graft prefabrication particularly to utilize for injuries with tissue loss. METHODS: Twenty-four Sprague-Dawley rats were allocated into three groups. 1.5 cm long peroneal nerve segment was excised, reversed in orientation, and used as autologous nerve graft. In conventional interpositional nerve graft group (Group 1), nerve defects were repaired in single-stage. In loop nerve graft prefabrication group (Group 2), grafts were sutured end-to-end (ETE) to the proximal peroneal nerve stumps. Distal ends of the grafts were sutured end-to-side to the peroneal nerve stumps 5 mm proximal to the ETE repair sites in first stage. In second stage, distal ends of the prefabricated grafts were transposed and sutured to distal nerve stumps. In staged conventional interpositional nerve graft group (Group 3), grafts were sutured ETE to proximal peroneal nerve stumps in first stage. Distal ends of the grafts and nerve stumps were tacked to the surrounding muscles until the final repair in second stage. Follow-up period was 4 weeks for each stage in Groups 2 and 3, and 8 weeks for Group 1. Peroneal function index (PFI), electrophysiology, and histological assessments were conducted after 8 weeks. P<0.05 was considered significant for statistical analysis. RESULTS: PFI results of Group 1 (-22.75±5.76) and 2 (-22.08±6) did not show statistical difference (p>0.05). Group 3 (-33.64±6.4) had a statistical difference compared to other groups (p<0.05). Electrophysiology results of Group 1 (16.19±2.15 mV/1.16±0.21 ms) and 2 (15.95±2.82 mV/1.17±0.16 ms) did not present statistical difference (p>0.05), whereas both groups had a statistical difference compared to Group 3 (10.44±1.96 mV/1.51±0.15 ms) (p<0.05). Axon counts of Group 1 (2227±260.4) and 3 (2194±201.1) did not have statistical difference (p>0.05), whereas both groups had significantly poor axon counts compared to Group 2 (2531±91.18) (p<0.05). CONCLUSION: Loop nerve graft prefabrication improved axonal regeneration without delay. Loop prefabrication can accelerate prolonged regeneration time for the injuries indicating a delayed nerve reconstruction. Higher axon counts derived with loop nerve prefabrication may even foster its investigation in immediate long nerve defect reconstructions in further studies.

Effect of hyperbaric oxygen therapy when combined with fresh and frozen platelet-rich plasma on chronic wound healing in rats.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) has an added dimension to the armamentarium of treating complicated chronic wounds. The purpose of this study is to investigate the effects of HBOT on chronic wounds when combined with fresh and frozen platelet-rich plasma (PRP). METHODS: Rats were divided into two main groups containing 18 rats in each group as HBOT received and non-received. Each group was divided into three subgroups as Group 1: Control, Group 2: Fresh, and Group 3: Frozen PRP applied. For PRP preparation, 10 rats were used. Histologic parameters including fibroblast, collagen fibers, lymphocytes, and vessels were evaluated by Clemex Vision Lite 3.5; wound sizes were evaluated by ImageJ digital analyzing program. RESULTS: In HBOT received group, the number of fibroblasts, collagen fibers, lymphocytes, and vessels in all fresh and frozen PRP applied and control subgroups were significantly higher than hyperbaric oxygen non-received group (p<0.05). In HBOT received group, wound surface area measurement values of control, fresh, and frozen PRP applied groups at 5-10-15 days were lower than HBOT non-received group. CONCLUSION: HBOT accelerates wound healing when combined with both fresh and frozen PRP. Frozen PRP is as effective as fresh form to be considered as an alternative in clinical setting.

Pharmacokinetics and Biodistribution of Tacrolimus after Topical Administration: Implications for Vascularized Composite Allotransplantation.

AIM: The high doses of oral tacrolimus (TAC) (1,2) necessary to prevent acute rejection (AR) after vascularized composite allotransplantation (VCA) are associated with systemic adverse effects. The skin is the most antigenic tissue in VCA and the primary target of AR. However, the short-term use of topical TAC (Protopic®), as an off-label adjunct to oral TAC, to treat AR episodes pro re nata (PRN), has yielded inconsistent results. There is lack of data on the pharmacokinetics and tissue distribution of topical TAC in VCA, that hampers our understanding of the reasons for unreliable efficacy. Toward this goal, we evaluated the ability of topical TAC to achieve high local tissue concentrations at the site of application with low systemic concentrations. MATERIALS AND METHODS: We assessed the pharmacokinetics and tissue distribution of topical TAC (Protopic®, 0.03%) after single or repeated topical application in comparison to those after systemic delivery in rats. Animals received a single topical application of TAC ointment (Group 1) or an intravenous (IV) injection of TAC (Group 2) at a dose of 0.5 mg/kg. In another experiment, animals received daily topical application of TAC ointment (Group 3), or daily intraperitoneal (IP) injection of TAC (Group 4) at a dose of 0.5 mg/kg for 7 days. TAC concentrations in blood and tissues were analyzed by Liquid Chromatography-Mass Spectrometry (LC/MS-MS). RESULTS: Following single topical administration, TAC was absorbed slowly with a Tmax of 4 h and an absolute bioavailability of 11%. The concentrations of TAC in skin and muscle were several folds higher than whole blood concentrations. Systemic levels remained subtherapeutic (< 3 ng/ml) with repeated once daily applications. CONCLUSION: Topical application of TAC ointment (Protopic®, 0.03%) at a dose of 0.5 mg/kg/day provided high concentrations in the local tissues with low systemic exposure. Repeated topical administration of TAC is well tolerated with no local or systemic adverse effects. This study confirms the feasibility of topical application of TAC for site specific graft immunosuppression and enables future applications in VCA.

Evaluation of Porcine Versus Human Mesenchymal Stromal Cells From Three Distinct Donor Locations for Cytotherapy.

Background: Mesenchymal stromal cell (MSC)-based cytotherapies fuel the hope for reduction of chronic systemic immunosuppression in allotransplantation, and our group has previously shown this capability for both swine and human cells. MSCs harvested from distinct anatomical locations may have different behavior and lead to different outcomes in both preclinical research and human trials. To provide an effective reference for cell therapy studies, we compared human and porcine MSCs from omental fat (O-ASC), subcutaneous fat (SC-ASC) and bone marrow (BM-MSC) under rapid culture expansion with endothelial growth medium (EGM). Methods: MSCs isolated from pigs and deceased human organ donors were compared for yield, viability, cell size, population doubling times (PDT), surface marker expression and differentiation potential after rapid expansion with EGM. Immunosuppressant toxicity on MSCs was investigated in vitro for four different standard immunosuppressive drugs. Immunomodulatory function was compared in mixed lymphocyte reaction assays (MLR) with/without immunosuppressive drug influence. Results: Human and porcine omental fat yielded significantly higher cell numbers than subcutaneous fat. Initial PDT was significantly shorter in ASCs than BM-MSCs and similar thereafter. Viability was reduced in BM-MSCs. Porcine MSCs were positive for CD29, CD44, CD90, while human MSCs expressed CD73, CD90 and CD105. All demonstrated confirmed adipogenic differentiation capacity. Cell sizes were comparable between groups and were slightly larger in human cells. Rapamycin revealed slight, mycophenolic acid strong and significant dose-dependent toxicity on viability/proliferation of almost all MSCs at therapeutic concentrations. No relevant toxicity was found for Tacrolimus and Cyclosporin A. Immunomodulatory function was dose-dependent and similar between groups. Immunosuppressants had no significant adverse effect on MSC immunomodulatory function. Discussion: MSCs from different harvest locations and donor species differ in terms of isolation yields, viability, PDT, and size. We did not detect relevant differences in immunomodulatory function with or without the presence of immunosuppressants. Human and pig O-ASC, SC-ASC and BM-MSC share similar immunomodulatory function in vitro and warrant confirmation in large animal studies. These findings should be considered in preclinical and clinical MSC applications.

Heterotopic Transplantation of Allogeneic Vertical Rectus Abdominis Myocutaneous Flaps in Miniature Swine.

BACKGROUND: Vascularized composite tissue allotransplantation (VCA) opens new possibilities for reconstruction of complex tissue defects, including upper extremity and facial transplantation. The main challenges in VCA transplantation are the side effects of long-term immunosuppression and chronic graft rejection. Translational preclinical animal models are crucial for VCA research to improve clinical outcomes and to study underlying immunologic mechanisms. Herein, we describe a novel, large animal, non-bone-bearing VCA model in inbred, swine leukocyte antigen-typed miniature swine. METHODS: Transplantation of vertical rectus abdominis myocutaneous (VRAM) flaps was performed between fully swine leukocyte antigen-mismatched miniature swine. The flaps were transferred to the posterolateral aspect of the neck of recipients and anastomosed to the common carotid artery and internal jugular vein. Different immunosuppressive drug regimens were used. Clinical graft evaluation was performed daily, and punch biopsies were taken for histology. RESULTS: Ten VRAM transplants were performed. The mean ischemia time was 89.4 min (SD ± 47), mean pedicle length 7.5 cm (SD ± 2), mean venous diameter 2.5 mm (SD ± 0.4), and mean arterial diameter 2.2 mm (SD ± 0.3). Follow-up demonstrated good correlation between clinical appearance and progression of graft rejection confirmed by histologic assessment. Complications were intraoperative cardiac arrest in one recipient and one flap loss due to venous compromise. CONCLUSIONS: VRAM transplantation in miniature swine is an appropriate preclinical VCA model, with the advantage of good clinical and histologic correlation during the course of rejection, as well as easy access to the graft. The availability of inbred, haplotyped animals allows studies across different major histocompatibility complex barriers in a non-bone-bearing VCA.

A Practical Noncontact Model to Create Standardized Experimental Burn Wounds of Any Thickness: Blue Beam Laser Pointer for Burn Induction.

The objective of this study was to describe a predictable and easy-to-use model that can create standardized burn wounds. A 450-nm 1000-mW blue beam laser pointer was used to create burn wounds on the dorsal skin of 24 Sprague Dawley rats. Twelve distinct areas of dorsal skin were pulsed for 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, and 23 seconds with the help of a punched plastic card template. Three groups of 8 animals were killed immediately after on the third day and on the seventh day of the procedure and tissue samples were taken for histological evaluation and measurements. A second-degree burn was obtained in all animals with 3 and 5 seconds of laser application on the same day, third day, and seventh day measurements. Seven seconds of application resulted in a burn depth of 84.87% of dermis on the application day which deepened to involve the whole dermal layer on the third and seventh day. Nine seconds and longer application times resulted in third-degree burn wounds. Burn induction with blue beam laser pointer is an easy-to-use, predictable and safe model to create a standardized burn wound of desired thickness.

Corrosion and bone healing of Mg-Y-Zn-Zr-Ca alloy implants: Comparative in vivo study in a non-immobilized rat femoral fracture model.

Biodegradable magnesium (Mg) alloys exhibit improved mechanical properties compared to degradable polymers while degrading in vivo circumventing the complications of permanent metals, obviating the need for surgical removal. This study investigated the safety and efficacy of Mg-Y-Zn-Zr-Ca (WZ42) alloy compared to non-degradable Ti6Al4V over a 14-week follow-up implanted as pins to fix a full osteotomy in rat femurs and as wires wrapped around the outside of the femurs as a cerclage. We used a fully load bearing model allowing implants to intentionally experience realistic loads without immobilization. To assess systemic toxicity, blood cell count and serum biochemical tests were performed. Livers and kidneys were harvested to observe any accumulation of alloying elements. Hard and soft tissues adjacent to the fracture site were also histologically examined. Degradation behavior and bone morphology were determined using micro-computed tomography scans. Corrosion occurred gradually, with degradation seen after two weeks of implantation with points of high stress observed near the fracture site ultimately resulting in WZ42 alloy pin fracture. At 14 weeks however, normal bone healing was observed in femurs fixed with the WZ42 alloy confirmed by the presence of osteoid, osteoblast activity, and new bone formation. Blood testing exhibited no significant changes arising from the WZ42 alloy compared to the two control groups. No recognizable differences in the morphology and more importantly, no accumulation of Mg, Zn, and Ca in the kidney and liver of rats were observed. These load bearing model results collectively taken, thus demonstrate the feasibility for use of the Mg-Y-Zn-Zr-Ca alloy for long bone fracture fixation applications.

Mycophenolic Acid for Topical Immunosuppression in Vascularized Composite Allotransplantation: Optimizing Formulation and Preliminary Evaluation of Bioavailability and Pharmacokinetics.

Mycophenolic acid (MPA), is the active form of the ester prodrug mycophenolate mofetil (MMF). MMF is an FDA approved immunosuppressive drug that has been successfully used in systemic therapy in combination with other agents for the prevention of acute rejection (AR) following solid organ transplantation (SOT) as well as in vascularized composite allotransplantation (VCA). Systemic use of MMF is associated with gastrointestinal adverse effects. Topical delivery of the prodrug could thus provide graft-targeted immunosuppression while minimizing systemic drug exposure. Our goal was to develop a topical formulation of MPA with optimal in vitro/in vivo characteristics such as release, permeation, and tissue bioavailability to enable safety and efficacy evaluation in clinical VCA. Permeation studies were performed with a solution of MPA (10 mg/ml). In vitro release and permeation studies were performed for different semisolid formulations (Aladerm, Lipoderm, emollient, and VersaBase) of MPA (1% w/w) using a Franz Diffusion Cell System (FDCS). In vivo pharmacokinetic characterization of MPA release from Lipoderm was performed in rats. MPA in solution exhibited a steady state flux (3.8 ± 0.1 µg/cm2/h) and permeability (1.1 × 10-7 ± 3.2 × 10-9 cm/s). MPA in Lipoderm exhibited a steady state flux of 1.12 ± 0.24 µg/cm2/h, and permeability of 6.2 × 10-09 ± 1.3 × 10-9 cm/s across the biomimetic membrane. The cumulative release of MPA from Lipoderm, showed a linear single-phase profile with a R2 of 0.969. In vivo studies with MPA in Lipoderm showed markedly higher local tissue MPA levels and lower systemic MPA exposure as compared to values obtained after intravenous delivery of the same dose of drug (p < 0.05). We successfully developed for the first time, a topical formulation of MPA in Lipoderm with optimal in vitro/in vivo permeability characteristics and no undesirable local or systemic adverse effects in vivo. Our study provides key preliminary groundwork for translational efficacy studies of topical MPA in pre-clinical large animal VCA models and for effectiveness evaluation in patients receiving VCA.

Targeted mesenchymal stem cell and vascular endothelial growth factor strategies for repair of nerve defects with nerve tissue implanted autogenous vein graft conduits.

Peripheral nerve gaps exceeding 1 cm require a bridging repair strategy. Clinical feasibility of autogenous nerve grafting is limited by donor site comorbidity. In this study we investigated neuroregenerative efficacy of autogenous vein grafts implanted with tissue fragments from distal nerve in combination with vascular endothelial growth factor (VEGF) or mesenchymal stem cells (MSCs) in repair of rat peripheral nerve defects. Six-groups of Sprague-Dawley rats (n = 8 each) were evaluated in the autogenous setting using a 1.6 cm long peroneal nerve defect: Empty vein graft (group 1), Nerve graft (group 2), Vein graft and nerve fragments (group 3), Vein graft and nerve fragments and blank microspheres (group 4), Vein graft and nerve fragments and VEGF microspheres (group 5), Vein graft and nerve fragments and MSCs (group 6). Nerve fragments were derived from distal segment. Walking track analysis, electrophysiology and nerve histomorphometry were performed for assessment. Peroneal function indices (PFI), electrophysiology (amplitude) and axon count results for group 2 were -9.12 ± 3.07, 12.81 ± 2.46 mV, and 1697.88 ± 166.18, whereas the results for group 5 were -9.35 ± 2.55, 12.68 ± 1.78, and 1566 ± 131.44, respectively. The assessment results did not reveal statistical difference between groups 2 and 5 (P > 0.05). The best outcomes were seen in group 2 and 5 followed by group 6. Compared to other groups, poorest outcomes were seen in group 1 (P ≤ 0.05). PFI, electrophysiology (amplitude) and axon count results for group 1 were -208.82 ± 110.69, 0.86 ± 0.52, and 444.50 ± 274.03, respectively. Vein conduits implanted with distal nerve-derived nerve fragments improved axonal regeneration. VEGF was superior to MSCs in facilitating nerve regeneration. © 2015 Wiley Periodicals, Inc. Microsurgery 36:578-585, 2016.

Recalcitrant caustic burn wound and definitive treatment with medial plantar flap.

Caustic chemicals cause destruction in tissues even long after the initial exposure. This study reported a case of recurrent graft lysis encountered throughout the treatment of a sodium hydroxide burn. A caustic burn on the ankle of a patient was reconstructed with split thickness skin grafts thrice in a period of four months. The burn site healed uneventfully after each skin grafting. However, weeks after each successful graft take, even though the patient did not experience any trauma at his operated ankle, an eczematous blistering at the skin graft site was observed. Thereafter, skin grafts almost totally sloughed over time even after each successful graft take. Six months after the initial burn and recurrent skin graft lysis, the defect site was reconstructed with medial plantar flap. At the postoperative ninth month follow-up, there was no sign of the blistering or skin loss at the burn area after definitive flap surgery. Recurrent graft lysis, in a few weeks after total skin graft take is an unusual complication for most of the burn cases. Caustic burns may have a deceptively superficial appearance concealing the chemical reactions that further damage the tissue. Therefore, early surgical interventions such as deep debridement and graft surgery should be kept in mind as primary treatment options.

Origin, Reality, and Clinical Importance of the Arcade of Struthers: An Anatomic Study.

The literature contains confusing and opposing views about the naming, prevalence, anatomic structure, and clinical significance of the arcade of Struthers. The conflicting rates of arcade (between 0% and 100%) prevalence found in the literature may be due to the varying definition of the arcade among the authors, as well as the dissection method. The present study aims to examine the structure to determine whether or not the arcade of Struthers exists through an anatomic dissection study of a fresh human cadaver and seeks to compare its findings with those in the literature. Twenty arms from fresh frozen cadavers were dissected. An arcade of Struthers was not found in any specimen. Study concluded that its existence is unproven, and the arcade of Struthers does not exist.

Changing the Donor Site Selection Concept of Facial Skin Expansion from Pure Healthy Tissue to Defect and Healthy Tissue Combination.

UNLABELLED: Facial defect reconstruction is a challenge for plastic surgeons due to unique esthetic and functional properties of the region. Facial tissue expansion provides an ideal reconstruction resource. However, the donor site is limited in the facial region. Thus, a cost-effective expansion management is crucial for an efficient reconstruction. In this article, the evolution of our donor site preference for tissue expansion from pure healthy tissue to a defect-healthy tissue combination is presented. Fifteen patients underwent skin reconstruction with local tissue expansion for facial and cervical defects. The full facial or cervical region including the defect and healthy tissue combination was determined as the donor expansion site. The donor site was not limited only to pure healthy tissue. The largest size rectangular expander suitable for the combined expandable donor site size was placed under the defect and healthy tissue border, paying attention to carry the expander far beneath the defect site. The defect site and most adjacent healthy tissue were expanded simultaneously. Major complications such as infection, hematoma, rupture, or flap necrosis were not observed. The expansion of defect-healthy tissue border presented successful reconstruction results with acceptable scars. In the traditional tissue expansion concept, using a large size expander to provide more abundant flap gain does not comply with the limited size of healthy donor site in the face. Expanding the whole facial region, without restriction of the defect, supplies excess donor tissue area for larger size expander use. Eventually, defect-healthy tissue border expansion with large expanders results in minimum final scar and less tissue loss in flap relocation and enables optimal flap gain. This method can easily be adapted to any tissue expansion site of the body. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Comparison of Treatments With Local Mesenchymal Stem Cells and Mesenchymal Stem Cells With Increased Vascular Endothelial Growth Factor Expression on Irradiation Injury of Expanded Skin.

INTRODUCTION: Radiation injury results in chronically ischemic tissue. Radionecrosis can be encountered in severe cases. Mesenchymal stem cells (MSCs) have a therapeutic effect on ischemia-related lesions. In here, effects of bone-marrow derived MSC and vascular endothelial growth factor (VEGF) gene-transfected MSC (VEGF-MSC) treatment on expanded skin with irradiation injury is investigated. METHODS: Silicone tissue expander (50 cm) was placed subcutaneously and expanded weekly up to 60 cm in 24 Sprague Dawley rats. Single fraction (30 Gy) radiotherapy was applied to the 2 × 2 cm area of the expanded skin. Dulbecco modified Eagle medium without cell component, MSCs, and VEGF-MSCs were injected subcutaneously at the irradiation-expansion sites. Skin samples were evaluated by histomorphometry and immunohistochemistry. Perfusion rate of the samples was assessed by scintigraphy. RESULTS: Epidermal thickness of irradiated-expanded skin was increased after MSC and VEGF-MSC treatments, whereas dermal and capsule thicknesses did not change. The MSC and VEGF-MSC treatments were effective in preserving, respectively, CD31 and VEGF expressions at a similar level as expanded skin after irradiation injury. The VEGF-MSC treatment significantly elevated CD31 levels in the irradiated tissue. Skin perfusion results were consistent with the CD31 and VEGF expressions. The MSC and VEGF-MSC treatments were effective in increasing proliferating cell nuclear antigen (PCNA) expression in irradiation zone. The VEGF-MSC treatment was efficient in reducing both expansion- and irradiation-related apoptosis. CONCLUSION: Vascular impairment and dermal insufficiency due to tissue expansion and irradiation injury can easily result in a wound hard to repair. The MSCs and VEGF-MSCs can promote neovascularization, reverse the effect of irradiation, and provide more durable soft tissue for expansion/implant reconstruction.

Avoiding Extended Scar in Skin Expansion: Alagoz Technique.

The principal aim of skin expansion is to provide additional donor tissue without extra donor-site morbidity. Most of the reports about tissue expansion are focused on the properties of expander. Donor-site decision is usually underestimated. Here, we offer to use the defect area and surrounding healthy tissue as the donor site.In 4 cases, expanders were placed just under the defect in a fashion to extend 1 to 2 cm more laterally toward the encircling healthy tissue. The expanded tissue was not mobilized for longer distances; thus, there was no loss in flap gain. The resulting final scar was linear or crescentic. In the Alagoz technique, tissue gain similar in size to the defect is sufficient for reconstruction. The simpler the flap, the best the resulting scar.