Experimental Models in Penile Transplantation: Translational Insights and Relevance to Clinical Application.

Animal research is an essential contributor to the medical achievements of the last century. The first step of studying a disease in animals is the development of a model which is relevant to the clinical situation in humans. Thus, a good animal model is the sine qua non of the experimental research.

Ten-Year Follow-Up of Lower Limb Replantation: Objective Evaluation With Gait Analysis.

The decision-making process for lower limb replantation involves several critical factors, such as age, comorbidities, ischemia time, type of injury, and psychosocial considerations. Advances in microsurgical techniques have led to a greater focus on enhancing functionality through limb salvage. To improve functional outcomes, it is essential to gain a better understanding of the current challenges in reconstruction and address them in future cases.

A World Update of Progress in Lower Extremity Transplantation: What's Hot and What's Not.

The field of vascularized composite allotransplantation (VCA) is the new frontier of solid organ transplantation (SOT). VCA spans life-enhancing/life-changing procedures such as upper extremity, craniofacial (including eye), laryngeal, tracheal, abdominal wall, penis, and lower extremity transplants. VCAs such as uterus transplants are life giving unlike any other SOT.

Osteocutaneous Fibular Flap for Reconstruction of Composite Metacarpal Defects Due to Gunshot Wounds.

Background: Gunshot wounds of the hand are challenging, as these injuries include bones, tendons neurovascular structures, and soft tissue. The osteocutaneous fibula flap has shown to be an excellent option for treating the composite defects, including bone and soft tissue. In this study, reconstructions of gunshot injuries of the metacarpal bones with a fibular flap are presented.

A Reversibly Thermoresponsive, Theranostic Nanoemulgel for Tacrolimus Delivery to Activated Macrophages: Formulation and In Vitro Validation.

Despite long-term immunosuppression, organ transplant recipients face the risk of immune rejection and graft loss. Tacrolimus (TAC, FK506, Prograf) is an FDA-approved keystone immunosuppressant for preventing transplant rejection. However, it undergoes extensive first-pass metabolism and has a narrow therapeutic window, which leads to erratic bioavailability and toxicity.

Novel cell-based strategies for immunomodulation in vascularized composite allotransplantation.

Purpose Of Review: Vascularized composite allotransplantation (VCA) has become a clinical reality in the past two decades. However, its routine clinical applications are limited by the risk of acute rejection, and the side effects of the lifelong immunosuppression. Therefore, there is a need for new protocols to induce tolerance and extend VCA survival.

Functional Reconstruction of Arches of the Foot With Vascularized Fibula Flap.

The skeletal integrity of the foot is as important as the soft tissue coverage of the foot. In this article, we present reconstruction of arches of foot with free fibula flap. Three patients with composite foot defects underwent reconstruction a with vascularized fibula flap.

Composite tissue xenopreservation: Preliminary results of staged VCA in rat to mouse model.

Background: The time between procurement and transplantation of composite tissues, especially regarding the limited donor pool, is a challenge effecting the outcomes of the transplantation. Current preservation techniques mainly include either cold preservation with a solution or machine perfusion using blood or certain oxygen-carrying solutions. However, none enables preservation beyond 24 h.

Peripheral nerve repair is associated with augmented cross-tissue inflammation following vascularized composite allotransplantation.

Introduction: Vascularized composite allotransplantation (VCA), with nerve repair/coaptation (NR) and tacrolimus (TAC) immunosuppressive therapy, is used to repair devastating traumatic injuries but is often complicated by inflammation spanning multiple tissues. We identified the parallel upregulation of transcriptional pathways involving chemokine signaling, T-cell receptor signaling, Th17, Th1, and Th2 pathways in skin and nerve tissue in complete VCA rejection compared to baseline in 7 human hand transplants and defined increasing complexity of protein-level dynamic networks involving chemokine, Th1, and Th17 pathways as a function of rejection severity in 5 of these patients. We next hypothesized that neural mechanisms may regulate the complex spatiotemporal evolution of rejection-associated inflammation post-VCA.

Tacrolimus before CTLA4Ig and rapamycin promotes vascularized composite allograft survival in MGH miniature swine.

Background: We evaluated the outcome of vertical rectus abdominus myocutaneous flap (VRAM) allotransplantation in a mini-pig model, using a combined co-stimulation blockade (Co-SB) and mechanistic target of rapamycin inhibition (mTORi)-based regimen, with or without preceding calcineurin inhibition (CNI).

Materials And Methods: VRAM allotransplants were performed between SLA-mismatched MGH miniature swine. Group A (n = 2) was treated continuously with the mTOR inhibitor rapamycin from day -1 in combination with the Co-SB agent cytotoxic T lymphocyte antigen 4-Ig (CTLA4-Ig) from post-operative day (POD) 0.

Implantable Biomaterials for Peripheral Nerve Regeneration-Technology Trends and Translational Tribulations.

The use of autografted nerve in surgical repair of peripheral nerve injuries (PNI) is severely limited due to donor site morbidity and restricted tissue availability. As an alternative, synthetic nerve guidance channels (NGCs) are available on the market for surgical nerve repair, but they fail to promote nerve regeneration across larger critical gap nerve injuries. Therefore, such injuries remain unaddressed, result in poor healing outcomes and are a limiting factor in limb reconstruction and transplantation.

A thermoresponsive hydrogel system for long-acting corticosteroid delivery into the paranasal sinuses.

Delivering localized treatment to the paranasal sinuses for diseases such as chronic rhinosinusitis (CRS) is particularly challenging because of the small natural openings leading from the sinuses that can be further obstructed by presence of inflammation. As such, oral steroids, topical nasal sprays or irrigation, and surgery can be utilized to treat persistent sinonasal inflammation, but there exists a need for post-operative options for long-term steroid delivery to prevent disease recurrence. In the present study, a Thermogel, Extended-release Microsphere-based-delivery to the Paranasal Sinuses (TEMPS) is developed with the corticosteroid mometasone furoate.

In situ recruitment of regulatory T cells promotes donor-specific tolerance in vascularized composite allotransplantation.

Vascularized composite allotransplantation (VCA) encompasses face and limb transplantation, but as with organ transplantation, it requires lifelong regimens of immunosuppressive drugs to prevent rejection. To achieve donor-specific immune tolerance and reduce the need for systemic immunosuppression, we developed a synthetic drug delivery system that mimics a strategy our bodies naturally use to recruit regulatory T cells (T) to suppress inflammation. Specifically, a microparticle-based system engineered to release the T-recruiting chemokine CCL22 was used in a rodent hindlimb VCA model.

The effect of thymus transplantation on donor-specific chimerism in the rat model of composite osseomusculocutaneous sternum, ribs, thymus, pectoralis muscles, and skin allotransplantation.

Introduction: Research on tolerance has proven that development of donor-specific chimerism (DSC) may accompany tolerance induction in vascularized composite allotransplantation (VCA). In this study, we aimed to determine the effect of thymus transplantation on the induction of DSC in rat VCA model of osseomusculocutaneous sternum (OMCS) and osseomusculocutaneous sternum and thymus (OMCST) allotransplantation.

Materials And Methods: A total of 20 Lewis-Brown Norway and Lewis rats, 5-6 weeks old, weighting between 120 and 150 g, were used in the study.

Treg-inducing microparticles promote donor-specific tolerance in experimental vascularized composite allotransplantation.

For individuals who sustain devastating composite tissue loss, vascularized composite allotransplantation (VCA; e.g., hand and face transplantation) has the potential to restore appearance and function of the damaged tissues.

Immunological considerations and concerns as pertinent to whole eye transplantation.

Purpose Of Review: The advent of clinical vascularized composite allotransplantation (VCA), offers hope for whole eye transplantation (WET) in patients with devastating vison loss that fails or defies current treatment options. Optic nerve regeneration and reintegration remain the overarching hurdles to WET. However, the realization of WET may indeed be limited by our lack of understanding of the singular immunological features of the eye as pertinent to graft survival and functional vision restoration in the setting of transplantation.

Demonstration of technical feasibility and viability of whole eye transplantation in a rodent model.

Introduction: Whole eye transplantation (WET) holds promise for vision restoration in devastating/disabling visual loss (congenital or traumatic) not amenable to surgical or neuroprosthetic treatment options. The eye includes multiple tissues with distinct embryonic lineage and differential antigenicity. Anatomically and immunologically, the eye is unique due to its avascular (cornea) and highly vascular (retina) components.

A New Composite Eyeball-Periorbital Transplantation Model in Humans: An Anatomical Study in Preparation for Eyeball Transplantation.

Background: Vascularized composite allotransplantation offers a new hope for restoration of orbital content and perhaps vision. The aim of this study was to introduce a new composite eyeball-periorbital transplantation model in fresh cadavers in preparation for composite eyeball allotransplantation in humans.

Methods: The composite eyeball-periorbital transplantation flap borders included the inferior border, outlined by the infraorbital rim; the medial border, created by the nasal dorsum; the lateral border, created by the lateral orbital rim; and the superior border, created by the superior part of the eyebrow.

Case Report: Late Reconstruction of the Land Mine-Injured Heel With an Osteomyocutaneous Composite Fibular Flap.

The heel comprises the epidermis, minimal subcutaneous tissue, a dense septum, and the calcaneus. Injury to any of these structures can impair the ability to walk. The soft tissue or calcaneal bone can be injured by trauma.

Three-layer primary closure of the bipedicled TRAM flap donor site for unilateralbreast reconstruction: a 15-year experience with 124 consecutive patients.

Background/aim: The pedicled transverse rectus abdominis myocutaneous (TRAM) flap remains widely used as a breast reconstruction technique. The bipedicled TRAM flap is not as preferable as it was formerly, mainly because of its donor site complications. However, in a number of situations, a bipedicled TRAM flap may be the only alternative.

Pre-expanded Thoracodorsal Artery Perforator Flap.

The size of the thoracodorsal artery perforator (TDAP) flap or pedicle, in general, may be found to be inadequate. Pre-expansion of the flap before harvest can be a solution to increase the size of the TDAP flap in such instances. The pre-expanded TDAP flap can be used to reconstruct large-sized defects with the advantage of primary closure of the donor site.

A new total hemiface allotransplantation model in rats.

Introduction: Vascularized composite allotransplantation (VCA), a new reconstructive option for patients suffering from extensive facial defects leads to superior functional and aesthetic outcomes compared to the standard autologous reconstruction. Among VCA recipients, each case involves different facial structures and tissues depending on the patient's injury, thus drawing conclusions on the mechanism of immune interactions between the donor and recipient is challenging. This study introduces a new total hemiface VCA model, including scalp, external ear, mystacial pad, premaxilla, upper/lower lids, nose, and upper/lower lips to evaluate the effect of transplantation of multitissue VCA on the recipient's immune response.

Challenging Breast Augmentations: The Influence of Preoperative Anatomical Features on the Final Result.

Background: Achieving satisfactory results may be difficult in augmentation mammaplasty patients in the presence of breast, chest wall, or vertebral deformities. These deformities have not been classified previously, and the impact of each deformity or combination of deformities has not been defined.

Objectives: The aims of this study are to determine the complicating factors in augmentation mammaplasty, to classify these factors according to their influence on surgical outcome, and to develop an identification system for simplifying the recognition of challenging cases.