Geoffroy C. Sisk

A bio-inspired swellable microneedle adhesive for mechanical interlocking with tissue

Achieving significant adhesion to soft tissues while minimizing tissue damage poses a considerable clinical challenge. Chemical-based adhesives require tissue-specific reactive chemistry, typically inducing a significant inflammatory response. Staples are fraught with limitations including high-localized tissue stress and increased risk of infection, and nerve and blood vessel damage. Here, inspired by the endoparasite Pomphorhynchus laevis which swells its proboscis to attach to its host’s intestinal wall, we have developed a biphasic microneedle array that mechanically interlocks with tissue through swellable microneedle tips, achieving ~ 3.5 fold increase in adhesion strength compared to staples in skin graft fixation, and removal force of ~ 4.5 N/cm2 from intestinal mucosal tissue. Comprising a poly(styrene)-block-poly(acrylic acid) swellable tip and non-swellable polystyrene core, conical microneedles penetrate tissue with minimal insertion force and depth, yet high adhesion strength in their swollen state. Uniquely, this design provides universal soft tissue adhesion with minimal damage, less traumatic removal, reduced risk of infection and delivery of bioactive therapeutics.

Vascularized composite tissue allotransplantation--state of the art.

Vascularized composite tissue allotransplantation is a viable treatment option for injuries and defects that involve multiple layers of functional tissue. In the past 15 yr, more than 150 vascularized composite allotransplantation (VCA) surgeries have been reported for various anatomic locations including – but not limited to – trachea, larynx, abdominal wall, face, and upper and lower extremities. VCA can achieve a level of esthetic and functional restoration that is currently unattainable using conventional reconstructive techniques.

Novel surgical technique for full face transplantation.

Background: Full face transplantation raises a new set of ethical concerns and technical difficulties when compared with partial face transplantation. Previously, it was thought that full face allografts must include bilateral superficial temporal and facial arteries, dictating the need for inclusion of donor parotid glands. This would lead to poor aesthetic outcomes and limit facial nerve coaptation to the level of the main trunk, which often results in synkinesias. The authors present a new approach to full facial allograft recovery based on blood supply from facial arteries alone. This approach eliminates the need to include parotid glands, enabling more distal coaptation of facial nerve branches and targeted innervation of effector muscles. The recovery can be reproducibly performed within 4 hours. Methods: Three mock cadaver dissections and three full face transplantations were performed. Results: Donor facial allografts were dissected in cranio-caudal and lateral-to-medial fashion. Individual facial nerve branches were cut medial to parotid glands and coapted to corresponding recipient nerve branches. With the exception of one parotid gland used to add bulk, parotids were generally not included in the allografts. Relevant sensory nerves were coapted. External carotid arteries were dissected, leaving only bilateral facial arteries as the primary arterial supply. All full facial allografts were well perfused immediately following transplantation and are surviving. Conclusions: The authors describe a new, simple, and reproducible technique of full facial allograft recovery that allows perfusion using only bilateral facial arteries. Their technique follows critical principles of targeted sensory and motor nerve coaptation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

CURRENT PRINCIPLES OF FACIAL ALLOTRANSPLANTATION: THE BRIGHAM AND WOMEN’S HOSPITAL EXPERIENCE

Background: Facial allotransplantation is a revolutionary operation that has at last introduced the possibility of nearly normal facial restoration to patients afflicted by the most severe cases of facial disfigurement. Methods: The facial transplantation team at Brigham and Women’s Hospital evaluated more than 20 patients as potential face transplant recipients; of these, six became face transplant candidates and underwent full screening procedures. The team performed facial allotransplantations in four of these patients between April of 2009 and May of 2011. This is the largest clinical volume of facial transplant recipients in the United States to date. Results: The authors have learned important lessons from each of these four unique cases and from the more than 20 patients that they have evaluated as potential face transplant recipients. The authors have translated lessons learned through direct experience into a set of fundamental surgical principles of the operation. Conclusions: The authors’ surgical principles emphasize safety, technical feasibility, preservation of functional facial units, and return of motor and sensory function. This article describes each of these principles along with their rationale and, in some instances, illustrates their application.

Facial allotransplantation: a 3-year follow-up report.

INTRODUCTION Long term follow-up of face transplant patients is fundamental to our understanding of risks and benefits of this procedure. Worldwide experience has shown that function improves gradually over time. METHODS In April of 2009, a multidisciplinary team at Brigham and Womens Hospital performed face transplantation on a male patient to address a severe facial defect caused by high-voltage burns. Physical and occupational therapy was performed for the first six post-operative months. Close monitoring of the patients functional recovery, immunosuppression, and quality of life was performed at set time points. RESULTS Three years after face transplantation, the patient has recovered near-normal sensation. Along with satisfactory aesthetic results, his motor function continues to improve, aiding his speech, facial expressions, and social interaction. Furthermore, the patient reports continued improvements in quality of life. Infectious, metabolic, and immunologic complications have been successfully managed in a team approach. Immunosuppression doses have been effectively reduced, and steroid therapy was withdrawn before the end of the first postoperative year. CONCLUSIONS The presented outcomes demonstrate the procedures growing role in reconstructive surgery as teams continue to focus their efforts on further optimization of immunosuppression and surgical technique.

Evolution of ethical debate on face transplantation.

Background: Face transplantation can provide improved quality of life to severely disfigured individuals. The unique challenges of face transplantation prompted much ethical discussion even before the first clinical case. Many deemed it unethical, because of issues ranging from the need for potentially harmful immunosuppression to the potential transfer of identity. Over time, the ethical debate surrounding face transplantation has evolved. Methods: In August of 2012, the authors performed a review of the scientific literature on the ethics of face transplantation, focusing on the evolution of the discussion from before to after the first clinical case in 2005. The authors conducted a primary search (73 peer-reviewed publications) in PubMed using combinations of the terms “ethics” and “face transplantation” and “opinions,” and a secondary search (37 peer-reviewed publications) retrieving publications cited in some of the primary search findings. In total, the authors reviewed 110 articles. Results: A series of 15 issues were addressed repeatedly throughout the reviewed articles. The authors observed an evolution of the general opinion regarding face transplantation: initially seen almost unanimously as an outlandish and morally objectionable procedure, it began to be accepted as a feasible and necessary treatment option for the most significant facial defects. Conclusion: With growing clinical experience globally, new ethical questions have arisen that must be addressed to move the field of face transplantation forward in an ethically sound manner.

Initial Experience of Dual Maintenance Immunosuppression With Steroid Withdrawal in Vascular Composite Tissue Allotransplantation

Current immunosuppression in VCA is largely based on the experience in solid organ transplantation. It remains unclear if steroids can be reduced safely in VCA recipients. We report on five VCA recipients who were weaned off maintenance steroids after a median of 2 months (mean: 4.8 months, range 2–12 months). Patients were kept subsequently on a low dose, dual maintenance consisting of tacrolimus and mycophenolate mofetil/mycophenloic acid with a mean follow‐up of 43.6 months (median = 40 months, range 34–64 months). Early and late acute rejections responded well to temporarily augmented maintenance, topical immunosuppression, and/or steroid bolus treatment. One late steroid‐resistant acute rejection required treatment with thymoglobulin. All patients have been gradually weaned off steroids subsequent to the treatment of acute rejections. Low levels of tacrolimus (<5 ng/mL) appeared as a risk for acute rejections. Although further experience and a cautious approach are warranted, dual‐steroid free maintenance immunosuppression appears feasible in a series of five VCA recipients.

Moist dressing coverage supports proliferation and migration of transplanted skin micrografts in full-thickness porcine wounds

Transplantation of skin micrografts in a 1:100 ratio regenerate the epidermis of full-thickness wounds in pigs within 14 days in a wet environment. The aim of the current study was to combine micrografts and commercially available moist dressings. We hypothesized that micrografts regenerate the epidermis when covered with a moist dressing. 5cm×5cm and 10cm×10cm full-thickness wounds were created on the backs of pigs. Wounds were transplanted with 0.8mm×0.8mm micrografts created from a split-thickness skin graft in a 1:100 ratio. 5cm×5cm wounds were treated with wound chambers, moist dressings or dry gauze (non-transplanted control group). 10cm×10cm wounds were compared to non-transplanted wounds, both covered with moist dressings. Reepithelialization was assessed in biopsies from day 10, 14 and 18 post-transplantation. 5cm×5cm transplanted wounds covered with moist dressings showed 69.5±20.6% reepithelialization by day 14 and 90.5±10.4% by day 18, similar to wounds covered with a wound chamber (63.9±16.7 and 86.2±11.9%, respectively). 18 days post-transplantation, 10cm×10cm transplanted wounds covered with moist dressings showed 66.1±10.3% reepithelialization, whereas nontransplanted wounds covered with moist dressings were 40.6±6.6% reepithelialized. We conclude that micrografts combined with clinically available moist dressings regenerate the epidermis of full-thickness wounds.

Vascular Communications Between Donor and Recipient Tissues After Successful Full Face Transplantation

The vascular reorganization after facial transplantation has important implications on future surgical planning. The purpose of this study was to evaluate blood flow (BF) after full face transplantation using wide area‐detector computed tomography (CT) techniques. Three subjects with severe craniofacial injury who underwent full face transplantation were included. All subjects underwent a single anastomosis bilaterally of the artery and vein, and the recipient tongue was preserved. Before and after surgery, dynamic volume CT studies were analyzed for vascular anatomy and blood perfusion. Postsurgical CT showed extensive vascular reorganization for external carotid artery (ECA) angiosome; collateral flows from vertebral, ascending pharyngeal or maxillary arteries supplied the branches from the recipient ECAs distal to the ligation. While allograft tissue was slightly less perfused when the facial artery was the only donor artery when compared to an ECA–ECA anastomosis (4.4 ± 0.4% vs. 5.7 ± 0.7%), allograft perfusion was higher than the recipient normal neck tissue. BF for the recipient tongue was maintained from contralateral/donor arteries when the lingual artery was sacrificed. Venous drainage was adequate for all subjects, even when the recipient internal jugular vein was anastomosed in end‐to‐end fashion on one side. In conclusion, dynamic CT identified adequate BF for facial allografts via extensive vascular reorganization.

Functional Outcomes after Bilateral Hand Transplantation: A 3.5-Year Comprehensive Follow-Up.

Background: Since the first successful hand transplantation in 1998, 72 patients have been operated on for unilateral/bilateral hand transplantation across 13 countries. There have been multiple studies evaluating the outcomes of hand transplantation; however, there is considerable variability among the outcome measures evaluated in these studies. Methods: This article reports functional outcomes in a patient with bilateral hand transplants at a mid-forearm level with serial follow-ups over 3.5 years. Different parameters used to study the functional outcomes include the Disabilities of the Arm, Shoulder, and Hand score, the Carroll test, the Hand Transplant Score System, the Short Form-36 Health Survey, and routine occupational therapy measures. Various task-oriented outcomes were also assigned to provide milestones to the recovery. Results: The patient had a Disabilities of the Arm, Shoulder, and Hand score of 40, a Carroll test score of 48 (right) and 49 (left), and a Hand Transplant Score System score of 58 (right) and 57.5 (left) at 3.5-year follow-up. Interestingly, his objective scores did not change significantly during the follow-up, but he continued to function quite independently and is subjectively pleased with his outcomes. Conclusions: Multiple functional outcome measures provide an objective way to follow patients who have undergone hand transplantation. The authors propose a series of measures to elucidate subtleties in functional gains. However, use of this series in isolation may belie subjectively good results. They also propose a series of milestones in the recovery to give a better real-world explanation of progress. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.