The standard in nipple reconstruction remains the autologous skin flap. Unfortunately, the results are not satisfying, with up to 75% loss of nipple projection over time. Existing studies ...investigated the use of primates as a source of implants. The authors hypothesized that the porcine nipple can serve as a perfect shape-supporting implant because of functional similarities to the human nipple. A decellularization protocol was developed to obtain an acellular nipple scaffold (ANS) for nipple reconstruction.
Tissue samples were collected from eight disease-free female Yorkshire pigs (60 to 70 kg) and then decellularized. The decellularization efficiency and extracellular matrix characterization was performed histologically and quantitatively (DNA, total collagen, elastin, and glycosaminoglycan content). In vitro and in vivo biocompatibility was determined by human dermal fibroblast culture and subcutaneous implantation of six ANSs in a single Yorkshire pig (60 to 70 kg), respectively. Inflammation and adverse events were monitored daily based on local clinical signs.
The authors showed that all cellular structures and 96% of DNA 321.7 ± 57.6 ng DNA/mg wet tissue versus 11.7 ± 10.9 ng DNA/mg wet tissue, in native and ANS, respectively ( P < 0.001) can be successfully removed. However, this was associated with a decrease in collagen 89.0 ± 11.4 and 58.8 ± 9.6 μg collagen/mg ( P < 0.001) and elastin 14.2 ± 1.6 and 7.9 ± 2.4 μg elastin/mg ( P < 0.05) and an increase in glycosaminoglycan content 5.0 ± 0.7 and 6.0 ± 0.8 ng/mg ( P < 0.05). ANS can support continuous cell growth in vitro and during preliminary biocompatibility tests in vivo.
This is a preliminary report of a novel promising ANS for nipple reconstruction, but more research is needed to validate results.
Breast cancer is very common among women. Treatment involves mastectomy, but its consequences affect patient mental well-being, and can lead to depression. Nipple-areola complex reconstruction is critical, and existing methods lead to unsatisfactory outcomes.
Background
A general belief is to consider elderly patients as poor candidates for free flap reconstruction, which does not reflect our 20‐year experience for breast reconstruction (BR). The aim of ...this study was to determine the safety and benefits of BR using deep inferior epigastric perforator (DIEP) free flap in the elderly population.
Methods
We conducted a retrospective study of all consecutive BRs using DIEP flaps in patients 65 years or older at the European Georges Pompidou Hospital from January 2011 to December 2019. Postoperative complications were reported as minor or major. We used a descriptive approach to analyze the main characteristics of the patients included. Surgical patient‐reported outcomes and quality of life were assessed using the validated BREAST‐Q questionnaire.
Results
Eighty‐three DIEP flaps were performed in 79 patients (4 bilateral flaps) for BR. Sixty‐six percent of the patients (52/79) did not present any complication. Total flap loss occurred in 3 BR (3.6%), arterial thrombosis in 4 BR (4.8%), and venous thrombosis in 8 BR (9.6%). The average duration of inpatient stay was 9.5 (±2.7) days. Forty‐one of 69 eligible patients completed the questionnaire (response rate 59.4%). Patients reported high satisfaction and well‐being scores. The mean Q score for psychosocial well‐being was 75.4 (±16.7) and 59 (±13.3) for satisfaction with breasts.
Conclusion
In our retrospective cohort, DIEP flap BR in elderly population had similar success and complication rates compared with those in younger patients, as well as high satisfaction scores. The free flap should be encouraged for BR in women over 65 years of age, and personal motivation as well as physiological age considered as main criteria for patient selection.
•Six hours of ex vivo subnormothermic machine perfusion (SNMP) of rodent vascularized composite allografts (VCA) is feasible using acellular oxygen carrier HBOC-201•SNMP results in superior tissue ...preservation compared to conventional static cold storage (SCS) preservation•Successful transplantation of VCA grafts preserved with 6 h of SNMP is feasible and 30-d•survival rates are comparable to SCS preserved graft
Machine perfusion is gaining interest as an efficient method of tissue preservation of Vascularized Composite Allografts (VCA). The aim of this study was to develop a protocol for ex vivo subnormothermic oxygenated machine perfusion (SNMP) on rodent hindlimbs and to validate our protocol in a heterotopic hindlimb transplant model.
In this optimization study we compared three different solutions during 6 h of SNMP (n = 4 per group). Ten control limbs were stored in a preservation solution on Static Cold Storage SCS). During SNMP we monitored arterial flowrate, lactate levels, and edema. After SNMP, muscle biopsies were taken for histology examination, and energy charge analysis. We validated the best perfusion protocol in a heterotopic limb transplantation model with 30-d follow up (n = 13). As controls, we transplanted untreated limbs (n = 5) and hindlimbs preserved with either 6 or 24 h of SCS (n = 4 and n = 5).
During SNMP, arterial outflow increased, and lactate clearance decreased in all groups. Total edema was significantly lower in the HBOC-201 group compared to the BSA group (P = 0.005), 4.9 (4.3-6.1) versus 48.8 (39.1-53.2) percentage, but not to the BSA + PEG group (P = 0.19). Energy charge levels of SCS controls decreased 4-fold compared to limbs perfused with acellular oxygen carrier HBOC-201, 0.10 (0.07-0.17) versus 0.46 (0.42-0.49) respectively (P = 0.002).
Six hours ex vivo SNMP of rodent hindlimbs using an acellular oxygen carrier HBOC-201 results in superior tissue preservation compared to conventional SCS.
Reconstructive techniques to repair severe tissue defects include the use of autologous fasciocutaneous flaps, which may be limited due to donor site availability or lead to complications such as ...donor site morbidity. A number of synthetic or natural dermal substitutes are in use clinically, but none have the architectural complexity needed to reconstruct deep tissue defects. The perfusion decellularization of fasciocutaneous flaps is an emerging technique that yields a scaffold with the necessary composition and vascular microarchitecture and serves as an alternative to autologous flaps. In this study, we show the perfusion decellularization of porcine fasciocutaneous flaps using sodium dodecyl sulfate (SDS) at three different concentrations, and identify that 0.2% SDS results in a decellularized flap that is efficiently cleared of its cellular material at 86%, has maintained its collagen and glycosaminoglycan content, and preserved its microvasculature architecture. We further demonstrate that the decellularized graft has the porous structure and growth factors that would facilitate repopulation with cells. Finally, we show the biocompatibility of the decellularized flap using human dermal fibroblasts, with cells migrating as deep as 150 µm into the tissue over a 7-day culture period. Overall, our results demonstrate the promise of decellularized porcine flaps as an interesting alternative for reconstructing complex soft tissue defects, circumventing the limitations of autologous skin flaps.
Vascularized Composite Allografts (VCA) such as hand, face, or penile transplant represents the cutting-edge treatment for devastating skin defects, failed by the first steps of the reconstructive ...ladder. Despite promising aesthetic and functional outcomes, the main limiting factor remains the need for a drastically applied lifelong immunosuppression and its well-known medical risks, preventing broader indications. Therefore, lifting the immune barrier in VCA is essential to tip the ethical scale and improve patients' quality of life using the most advanced surgical techniques. De novo creation of a patient-specific graft is the upcoming breakthrough in reconstructive transplantation. Using tissue engineering techniques, VCAs can be freed of donor cells and customized for the recipient through perfusion-decellularization-recellularization. To develop these new technologies, a large-scale animal VCA model is necessary. Hence, swine fascio-cutaneous flaps, composed of skin, fat, fascia, and vessels, represent an ideal model for preliminary studies in VCA. Nevertheless, most VCA models described in the literature include muscle and bone. This work reports a reliable and reproducible technique for saphenous fascio-cutaneous flap harvest in swine, a practical tool for various research fields, especially vascularized composite tissue engineering.
•We bioengineered rat fibroblasts to secrete a biomarker: Gaussia Luciferase.•Machine perfusion was used to engraft these genetically modified cells in rat limbs.•After transplantation we could track ...the biomarker secretion for 4 days.•It is the first step toward engraftment of biosensor cells before transplantation.•Vascularized Composite Allotransplantation would benefit from in situ cell therapy.
Transplantation of the hand or face, known as vascularized composite allotransplantation (VCA), has revolutionized reconstructive surgery. Notwithstanding, there are still several areas of improvement to mitigate immune rejection while sparing systemic adverse effects. The goal of this study was to evaluate the engraftment and viability of a genetically modified cell population pre-engrafted into a VCA transplant, to potentially act as a local biosensor to report and modify the graft in vivo. A rat fibroblast cell line genetically modified to secrete Gaussia-Luciferase (gLuc), which served as a constitutive biomarker of cells, was incorporated into a VCA to study the viability of biosensor cells in a syngeneic rat heterotopic partial hindlimb transplantation model.
Five perfusions were first performed as engineering runs to have a stable limb perfusion protocol, followed by 3 perfusions to analyze the cell engraftment during machine perfusion, and finally 4 perfusions to study in vivo persistence of the cell biosensors. Blood samples were collected to monitor gLuc secretion during perfusion and postoperatively. A time-dependent increase in gLuc secretion in the limb perfusion outflow during machine perfusion indirectly verified the presence of biosensors within the graft. After the ex vivo perfusion, VCA hindlimbs were analyzed for near infrared fluorescence emission that showed a presence of dyed engineered cells in all areas of the limbs. Postoperatively, gLuc was detectable 4 to 5 days after transplantation (W = 16, P = .02857). This study demonstrated that engineered cells could be successfully preimplanted into VCAs—an important step toward development of an in vivo biosensor platform to use in modulating acute VCA outcomes.
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