Flexor tendon injuries: Repair & Rehabilitation.

Flexor tendon injuries are common and occur mostly by penetrating trauma. Suspected flexor tendon injuries require a thorough clinical assessment and often are not isolated injuries. A detailed understanding of flexor tendon anatomy and spatial relationships is essential, especially when repairing multi-tendon injuries. Principles of flexor tendon repair include a strong suture construct, minimising gap formation between tendon ends, preserving tendon blood supply and providing a smooth repair interface. Moreover, adequate exposure of the zone of injury using full-thickness skin flaps and preservation of neurovascular and pulley structures is essential. In this article an overview of contemporary management strategies is presented. Today's hand surgeons and therapists can choose from a variety of treatment options when managing these important and potentially life-changing injuries.

Embryonic stem cell extracts improve wound healing in diabetic mice.

AIMS/HYPOTHESIS: Impaired wound healing significantly impacts morbidity and mortality in diabetic patients, necessitating the development of novel treatments to improve the wound healing process. We here investigated the topical use of acellular embryonic stem cell extracts (EXTs) in wound healing in diabetic db/db mice. METHODS: Wounds were induced in diabetic db/db mice, which were subsequently treated with EXTs, with 3T3 fibroblast cell line protein extracts (3T3XTs) or with saline as a control. Pathology and mechanistic assays were then performed. RESULTS: The in vivo topical administration of EXTs facilitates wound closure, contraction and re-epithelialization. Moreover, EXTs reduced the number of wound-infiltrating CD45+ inflammatory cells and increased the rate of repair and of angiogenesis as compared to controls. Interestingly, the EXT effect was partly enhanced by the use of a collagen-based biocompatible scaffold. In vivo, topical administration of EXTs increased the percentage of regulatory T cells in the wounded tissue, while in vitro EXT treatment reduced T cell-mediated IFN-γ production. Proteomic screening revealed 82 proteins differentially segregating in EXTs as compared to 3T3 extracts, with APEX1 identified as a key player for the observed immunomodulatory effect of EXTs. CONCLUSIONS: EXTs are endowed with immunoregulatory and anti-inflammatory properties; their use improves wound healing in diabetic preclinical models.

Increasing Fat Graft Retention in Irradiated Tissue after Preconditioning with External Volume Expansion.

BACKGROUND: Fat grafting is an adjuvant that may improve the quality of radiation-damaged tissue. However, fat grafting for volume restoration in irradiated sites may be less effective because of a poorly vascularized fibrotic recipient bed. External volume expansion has emerged as a potential technique to prepare the recipient sites for improved survival of grafted fat. The authors previously demonstrated increased vasculature with external volume expansion stimulation of irradiated tissues. The authors now hypothesize that external volume expansion's improvements in recipient-site vascularity will increase the volume retention and quality of fat grafts in fibrotic irradiated sites. METHODS: Athymic mice were irradiated until development of chronic radiation injury. Then, the irradiated site was stimulated by external volume expansion (external volume expansion group), followed by subcutaneous fat grafting. Grafts in an irradiated site without external volume expansion stimulation (irradiated control group) and grafts in a healthy nonirradiated (nonirradiated control group) site were used as controls. All grafts were monitored for 8 weeks and evaluated both histologically and by micro-computed tomography for analysis of volume retention. RESULTS: Hyperspectral imaging confirmed a 25 percent decrease in vascularity of irradiated tissue (irradiated control group) compared with nonirradiated tissue (nonirradiated control group). Grafts in the irradiated control group retained 11 percent less volume than grafts in the nonirradiated control group. The experimental external volume expansion group achieved a 20 percent (p = 0.01) increase in retained graft volume compared with the irradiated control group. CONCLUSIONS: External volume expansion stimulation can mitigate the effects of irradiation at the recipient site and in turn help preserve fat graft volume retention. Possible mechanisms include increased vascularity, adipogenic conversion, and increased compliance of a fibrotic recipient site.

Leeching as Salvage Venous Drainage in Ear Reconstruction: Clinical Case and Review of Literature.

BACKGROUND: Ear avulsion is a rare complication of different traumas, such as car accidents, human or animal bites and stab wounds, and can result in dramatic cosmetic consequences for the patient. Ear replantation, revascularization, and reattachment are the options offering best aesthetic results. But venous outflow insufficiency is responsible for a high rate of failures. Leeching is one the most efficient methods to relieve venous congestion. It has been used as an alternative venous outflow in case of severe impairment of the physiologic one. METHODS: We present a case of successful rescue of a congested reattached ear by leeching after subtotal avulsion, along with a review of the literature on cases of avulsed auricle reconstruction salvaged by hirudotherapy. Data were collected and analyzed to identify a best regimen to deal with venous congestion. RESULTS: More than 130 cases of avulsed auricle savage are described in the literature, in a fourth of which leech therapy was used in the management of venous congestion. DISCUSSION: In case of both venous outflow deficit or absence, leeches are a potentially successful option to correct the congestion while new veins reestablish normal physiology. The need for anticoagulant/antiaggregant therapy, antibiotics, and often blood transfusion are the main pitfalls of leeching. CONCLUSION: Leeches can be considered a salvage method for ear replantation and reattachment in those cases that lack venous outflow in the presence of valid arterial inflow.

Surgical Otoplasty: An Evidence-Based Approach to Prominent Ears Correction.

Otoplasty is one of the first procedures learned during residency. A myriad of surgical techniques and nuances exist. Many have merit, some are ineffective, some destructive, and some frankly fanciful. Adopting an effective and safe technique should be based on proven efficacy and effectiveness to avoid early disappointments. We present a review of traditional otoplasty techniques and more recent innovations. Their pros and cons are discussed in view of the relative risks/benefits balance. Recurrence rates are low for most techniques. Some techniques carry a higher risk of significant complications. A ladder approach preferring techniques that minimize cartilage damage appears advisable.

Moderate-Intensity Intermittent External Volume Expansion Optimizes the Soft-Tissue Response in a Murine Model.

BACKGROUND: Intermittent external volume expansion using suction enhances the vascular network of soft tissues, possibly increasing fat graft survival. However, the optimal kinetics of application have not been determined. Based on their previous experience, the authors hypothesized that moderate-intensity intermittent external volume expansion application may further enhance both the angiogenic and adipogenic potential. METHODS: Fifty 12-week-old wild-type mice were assigned to five experimental groups (n = 10 per group) and underwent five different intermittent applications of external volume expansion (i.e., single-application control, low-intensity, moderate-intensity, and two groups of high-intensity). Five days after the final stimulation, skin biopsy specimens were obtained from stimulated and contralateral nonstimulated areas. Microscopic sections were analyzed for angiogenesis, skin remodeling, and adipogenesis. RESULTS: Moderate-intensity intermittent stimulation (0.5 hour, 6 times/day for 5 days at -25 mmHg suction) almost doubled cutaneous vascular density (1.9-fold increase), induced skin thickening (1.9-fold increase), and expanded the subcutaneous tissue (2.3-fold increase) compared with control. External volume expansion kinetics did not affect tissue inflammation at 5 days after treatment. High-intensity intermittent stimulations also increased the density of blood vessels (1.6-fold increase compared with controls) but caused tissue damage, whereas low-intensity external volume expansion did not induce significant changes. CONCLUSION: Application of moderate-intensity intermittent external volume expansion optimizes induction of angiogenesis and adipogenesis in soft tissues without tissue damage, holding potential for time-effective recipient-site preconditioning before fat grafting.

Overexpressing IRS1 in Endothelial Cells Enhances Angioblast Differentiation and Wound Healing in Diabetes and Insulin Resistance.

The effect of enhancing insulin's actions in endothelial cells (ECs) to improve angiogenesis and wound healing was studied in obesity and diabetes. Insulin receptor substrate 1 (IRS1) was overexpressed in ECs using the VE-cadherin promoter to create ECIRS1 TG mice, which elevated pAkt activation and expressions of vascular endothelial growth factor (VEGF), Flk1, and VE-cadherin in ECs and granulation tissues (GTs) of full-thickness wounds. Open wound and epithelialization rates and angiogenesis significantly improved in normal mice and high fat (HF) diet-induced diabetic mice with hyperinsulinemia in ECIRS1 TG versus wild type (WT), but not in insulin-deficient diabetic mice. Increased angioblasts and EC numbers in GT of ECIRS1 mice were due to proliferation in situ rather than uptake. GT in HF-fed diabetic mice exhibited parallel decreases in insulin and VEGF-induced pAkt and EC numbers by >50% without changes in angioblasts versus WT mice, which were improved in ECIRS1 TG mice on normal chow or HF diet. Thus, HF-induced diabetes impaired angiogenesis by inhibiting insulin signaling in GT to decrease the differentiation of angioblasts to EC, which was normalized by enhancing insulin's action targeted to EC, a potential target to improve wound healing in diabetes and obesity.

Induction of Adipogenesis by External Volume Expansion.

BACKGROUND: External volume expansion by suction is used to prepare the recipient site for fat grafting by increasing its compliance and vascularity. The authors previously developed a mouse model for external volume expansion and demonstrated its pro-proliferative and angiogenic effects. Increased thickness of the subcutaneous tissue was also observed. This study was thus designed to assess the adipogenic potential of external volume expansion stimulation. METHODS: A miniaturized external volume expansion device consisting of a rubber dome connected to a -25 mmHg suction source was applied to the dorsum of mice for a single 2-hour stimulation or for 2 hours daily for 5 days. Tissues were harvested up to 48 hours after the last stimulation and analyzed for edema, inflammation, and adipocyte content by staining for hematoxylin and eosin, CD45, and perilipin-A. Expression of peroxisome proliferator-activated receptor-γ (proadipogenic factor) and preadipocyte factor 1 (preadipocyte marker) was evaluated by Western blot analysis. RESULTS: Both a 2-hour stimulation and cyclical 2-hour stimulation for 5 days induced 1.5- and 1.9-fold increases in the number of adipocytes per millimeter. Edema was present in the immediate poststimulation period, and inflammation was seen 2 days later. Peroxisome proliferator-activated receptor-γ was increased at the end of stimulation. CONCLUSIONS: Stretch is known to stimulate proliferation, whereas edema and inflammation are both emerging proadipogenic factors. Their combination in external volume expansion seems to produce proadipogenic effects, seen even after a single 2-hour stimulation.

Hyperspectral Imaging as an Early Biomarker for Radiation Exposure and Microcirculatory Damage.

BACKGROUND: Radiation exposure can lead to detrimental effects in skin microcirculation. The precise relationship between radiation dose received and its effect on cutaneous perfusion still remains controversial. Previously, we have shown that hyperspectral imaging (HSI) is able to demonstrate long-term reductions in cutaneous perfusion secondary to chronic microvascular injury. This study characterizes the changes in skin microcirculation in response to varying doses of ionizing radiation and investigates these microcirculatory changes as a possible early non-invasive biomarker that may correlate with the extent of long-term microvascular damage. METHODS: Immunocompetent hairless mice (n = 66) were exposed to single fractions of superficial beta-irradiation in doses of 0, 5, 10, 20, 35, or 50 Gy. A HSI device was utilized to measure deoxygenated hemoglobin levels in irradiated and control areas. HSI measurements were performed at baseline before radiation exposure and for the first 3 days post-irradiation. Maximum macroscopic skin reactions were graded, and histological assessment of cutaneous microvascular densities at 4 weeks post-irradiation was performed in harvested tissue by CD31 immunohistochemistry. RESULTS: CD31 immunohistochemistry demonstrated a significant correlation (r = 0.90, p < 0.0001) between dose and vessel density reduction at 4 weeks. Using HSI analysis, early changes in deoxygenated hemoglobin levels were observed during the first 3 days post-irradiation in all groups. These deoxygenated hemoglobin changes varied proportionally with dose (r = 0.98, p < 0.0001) and skin reactions (r = 0.98, p < 0.0001). There was a highly significant correlation (r = 0.91, p < 0.0001) between these early changes in deoxygenated hemoglobin and late vascular injury severity assessed at the end of 4 weeks. CONCLUSION: Radiation dose is directly correlated with cutaneous microvascular injury severity at 4 weeks in our model. Early post-exposure measurement of cutaneous deoxygenated hemoglobin levels may be a useful biomarker for radiation dose reconstruction and predictor for chronic microvascular injury.

Diffusion and perfusion: the keys to fat grafting.

BACKGROUND: Fat grafting is now widely used in plastic surgery. Long-term graft retention can be unpredictable. Fat grafts must obtain oxygen via diffusion until neovascularization occurs, so oxygen delivery may be the overarching variable in graft retention. METHODS: We studied the peer-reviewed literature to determine which aspects of a fat graft and the microenvironment surrounding a fat graft affect oxygen delivery and created 3 models relating distinct variables to oxygen delivery and graft retention. RESULTS: Our models confirm that thin microribbons of fat maximize oxygen transport when injected into a large, compliant, well-vascularized recipient site. The "Microribbon Model" predicts that, in a typical human, fat injections larger than 0.16 cm in radius will have a region of central necrosis. Our "Fluid Accommodation Model" predicts that once grafted tissues approach a critical interstitial fluid pressure of 9 mm Hg, any additional fluid will drastically increase interstitial fluid pressure and reduce capillary perfusion and oxygen delivery. Our "External Volume Expansion Effect Model" predicts the effect of vascular changes induced by preoperative external volume expansion that allow for greater volumes of fat to be successfully grafted. CONCLUSIONS: These models confirm that initial fat grafting survival is limited by oxygen diffusion. Preoperative expansion increases oxygen diffusion capacity allowing for additional graft retention. These models provide a scientific framework for testing the current fat grafting theories.

Mechanoregulation of Angiogenesis in Wound Healing.

Significance: Mechanical forces are important regulators of cell and tissue function. Endothelial cells proliferate in response to tissue stretch and the mechanical properties of the environment direct capillary sprouting and growth. As the vascular network is a key factor in physiology and disease, control of the vascularity by means of mechanical forces could lead to the development of innovative therapeutic strategies. Recent Advances: Increased understanding of mechanobiology has stimulated translational research and allowed the development and optimization of clinical devices that exploit mechanical forces for the treatment of diseases, in particular in the field of wound healing. Stretching in distraction osteogenesis and tissue expansion induces neogenesis of well-vascularized tissues. In micro-deformational wound therapy, micro-mechanical distortions of the wound bed stimulate cell proliferation and angiogenesis by stretching resident cells to improve healing of difficult wounds. Relief from tension antagonizes proliferation and angiogenesis in primarily closed wounds allowing for better scar quality. Critical Issues: The integration of mechanobiology into traditional cell biology and pathophysiology in general is not yet complete and further research is needed to fill existing gaps, in particular in the complexity of in vivo conditions. Future Directions: Still largely unexplored approaches based on mechanical perturbation of the micro-/macro-environment can be devised to overcome the limits of current strategies in a broad spectrum of clinical conditions.

Greater surgical precision of a flexible carbon dioxide laser fiber compared to monopolar electrosurgery in porcine myometrium.

The objective of this experimental animal study was to compare the surgical precision of a flexible CO2 laser fiber with that of monopolar electrosurgery in porcine myometrium. The subjects were 6 live adult non-pregnant female pigs. Linear injury to the uterine horns was created using a flexible CO2 laser fiber at 5W, 10W, and 15W and with monopolar electrosurgery at 10W, 20W, 30W, and 40W in both cut and coagulation modes. Hysterectomy was then performed in the live animals. Cross-sections of the tissue were processed and stained using Masson trichrome to differentiate damaged from undamaged myometrium. Measurement means were compared using analysis of variance with Tukey honest significant difference correction; p <.05 indicated significance. Incision width of the laser at 5W and 10W was significantly less than both monopolar coagulation at all power settings and monopolar cut at 30W and 40W (all p <.01), at 5W was also significantly less than monopolar cut at 10W (p = .03), and at 15W was significantly less than monopolar coagulation at 40W (p = .001). Incision depth of the laser at 5W was significantly less than monopolar coagulation at 40W and laser at 15W (both p = .01), at 15W was significantly greater than monopolar coagulation at 10W and monopolar cut at 10, 20, and 30W (p ≤.01), and increased proportional to power for all 3 energy types. Collateral thermal damage width at all laser power settings was significantly less than at all monopolar coagulation power settings (p ≤.04) with the exception of the laser at 15W compared with monopolar coagulation at 10W (p = .30), and at all laser power settings was significantly less than at all monopolar coagulation power settings (p <.001). Collateral thermal damage depth of the laser at 5W and 10W was significantly less than monopolar cut at 30W (p ≤.002) and increased proportional to power in monopolar coagulation mode but remained constant with the laser. Incising efficiency of the laser at 5W was significantly greater than monopolar coagulation at 10W (p = .04), at 10W was significantly greater than at all monopolar power settings (p ≤.007) except cut at 40W (p = .29), and at 15W was significantly greater than that of every other energy type and power setting tested (p ≤.04). These findings support the hypothesis that CO2 laser energy delivered via a flexible fiber system would exhibit greater surgical precision than monopolar electrosurgery, in both cut and coagulation modes, as defined by 3 parameters: incising efficiency, changes in incision depth compared with width as power increases, and variability in the resulting incision measurements. Because increased thermal damage has been associated with delayed tissue necrosis and adhesion formation, these findings prompt the design of a comparative survival animal study to assess additional clinically relevant parameters.

The role of mouse mast cell proteases in the proliferative phase of wound healing in microdeformational wound therapy.

BACKGROUND: Stored in the secretory granules of cutaneous mouse mast cells are mouse mast cell proteases (mMCP-4, -5, and -6). Using transgenic mouse lines that lacked these enzymes, it was shown that mMCP-4 and mMCP-5 modulate the outcome of burn-induced skin injury. Whether or not these proteases also play a role in the repair of surgically damaged skin, with or without microdeformational wound therapy, remains to be determined. METHODS: Wild-type C57BL/6 mice and transgenic C57BL/6 mouse lines lacking mMCP-4, -5, or -6 were subjected to surgical wounding of their skin. Wounds were splinted with a stabilizing patch, and the mice received either microdeformational wound therapy (n = 5) or occlusive dressing (n = 5) for 7 days. Wound healing parameters were assessed in the proliferative phase. RESULTS: Cell proliferation in the wounded wild-type mice receiving microdeformational wound therapy was 60 ± 3 percent. Cell proliferation was only 35 ± 5 percent, 25 ± 5 percent, and 45 ± 4 percent for the treated mMCP-4-, mMCP-5-, and mMCP-6-null mice, respectively (p = 0.005). Blood vessel sprouting was higher in the control mice with microdeformational wound therapy (170 ± 40 vessels/high-power field) compared with mouse mast cell protease 6-null mice with microdeformational wound therapy (70 ± 20 vessels/high-power field; p = 0.005), and higher in the control mice with occlusive dressing (110 ± 30 vessels/high-power field) compared with mMCP-4-null mice with occlusive dressing (50 ± 20 vessels/high-power field; p = 0.01). Qualitatively, the granulation tissue of all the protease-deficient groups receiving microdeformational wound therapy was disrupted. CONCLUSION: Results suggest that mouse mast cell proteases 4, 5, and 6 are mediators of the critical role mast cells play in microdeformational wound therapy in the proliferative phase of healing.