Zita M. Jessop

An algorithmic approach to perineal reconstruction after cancer resection--experience from two international centers.

AimThis paper aims to simplify the approach to reconstruction of the perineum after resection of malignancies of the anal canal, lower rectum, vulva, and vagina. Materials and MethodsThe data were collected from 2 centers, namely, Addenbrooke’s Hospital, University of Cambridge, United Kingdom and Christchurch Hospital, University of Otago, New Zealand. All patients who underwent perineal reconstruction from 1997 to 2009 at Christchurch Hospital (13 years) and 2001 to 2009 at Addenbrooke’s Hospital (9 years) were included. The diagnosis (indication), primary surgery, reconstructive surgery, complications, tumor outcomes (recurrence and survival), and follow-up were entered into a database (Microsoft Excel; Redmond, Wash). The incidence of previous radiotherapy, requirement for adjuvant radiotherapy, and length of inpatient stay were also recorded. ResultsForty-six patients were identified for this study—13 in New Zealand and 33 in Cambridge. Indications for perineal reconstruction included resection of anal and rectal malignancies (24), vulval and vaginal malignancy (19), perineal sarcoma (1), and perineal squamous cell carcinoma arising in an enterocutaneous fistula (Table 1). The reconstructive strategies adopted included rectus abdominis myocutaneous flaps (26), gluteal fold flaps (9), gracilis V-Y or advancement flaps (7) and others (4), gluteal rotation flaps (1), local flap (2), and free latissimus dorsi flaps (1). ConclusionsAlthough various surgeons performed the reconstructive surgeries at 2 different centers, the essential approach remained the same. Smaller defects were best treated by local flaps, whereas the rectus abdominis flap remained the standard option for larger defects that additionally required closure of dead space. On the basis of our 2 center experience, we propose a simple algorithm to facilitate the planning of reconstructive surgery for the perineum.

Transforming healthcare through regenerative medicine

Regenerative medicine therapies, underpinned by the core principles of rejuvenation, regeneration and replacement, are shifting the paradigm in healthcare from symptomatic treatment in the 20th century to curative treatment in the 21st century. By addressing the reasons behind the rapid expansion of regenerative medicine research and presenting an overview of current clinical trials, we explore the potential of regenerative medicine to reshape modern healthcare.

Adipose regeneration and implications for breast reconstruction: update and the future.

The evolution of breast reconstruction and management of breast cancer has evolved significantly since the earliest descriptions in the Edwin Smith Papyrus (3,000 BC). The development of surgical and scientific expertise has changed the way that women are managed, and plastic surgeons are now able to offer a wide range of reconstructive options to suit individual needs. Beyond the gold standard autologous flap based reconstructions, regenerative therapies promise the elimination of donor site morbidity whilst providing equivalent aesthetic and functional outcomes. Future research aims to address questions regarding ideal cell source, optimisation of scaffold composition and interaction of de novo adipose tissue in the microenvironment of breast cancer.

3D bioprinting for reconstructive surgery: Principles, applications and challenges

Despite the increasing laboratory research in the growing field of 3D bioprinting, there are few reports of successful translation into surgical practice. This review outlines the principles of 3D bioprinting including software and hardware processes, biocompatible technological platforms and suitable bioinks. The advantages of 3D bioprinting over traditional tissue engineering techniques in assembling cells, biomaterials and biomolecules in a spatially controlled manner to reproduce native tissue macro-, micro- and nanoarchitectures are discussed, together with an overview of current progress in bioprinting tissue types relevant for plastic and reconstructive surgery. If successful, this platform technology has the potential to biomanufacture autologous tissue for reconstruction, obviating the need for donor sites or immunosuppression. The biological, technological and regulatory challenges are highlighted, with strategies to overcome these challenges by using an integrated approach from the fields of engineering, biomaterial science, cell biology and reconstructive microsurgery.

CCR8 Expression Defines Tissue-Resident Memory T Cells in Human Skin

Human skin harbors two major T cell compartments of equal size that are distinguished by expression of the chemokine receptor CCR8. In vitro studies have demonstrated that CCR8 expression is regulated by TCR engagement and the skin tissue microenvironment. To extend these observations, we examined the relationship between CCR8+ and CCR8− skin T cells in vivo. Phenotypic, functional, and transcriptomic analyses revealed that CCR8+ skin T cells bear all the hallmarks of resident memory T cells, including homeostatic proliferation in response to IL-7 and IL-15, surface expression of tissue localization (CD103) and retention (CD69) markers, low levels of inhibitory receptors (programmed cell death protein 1, Tim-3, LAG-3), and a lack of senescence markers (CD57, killer cell lectin-like receptor subfamily G member 1). In contrast, CCR8− skin T cells are heterogeneous and comprise variable numbers of exhausted (programmed cell death protein 1+), senescent (CD57+, killer cell lectin-like receptor subfamily G member 1+), and effector (T-bethi, Eomeshi) T cells. Importantly, conventional and high-throughput sequencing of expressed TCR β-chain (TRB) gene rearrangements showed that these CCR8-defined populations are clonotypically distinct, suggesting unique ontogenies in response to separate antigenic challenges and/or stimulatory conditions. Moreover, CCR8+ and CCR8− skin T cells were phenotypically stable in vitro and displayed similar levels of telomere erosion, further supporting the likelihood of a nonlinear differentiation pathway. On the basis of these results, we propose that long-lived memory T cells in human skin can be defined by the expression of CCR8.

the challenge for reconstructive surgeons in the twenty-first century: manufacturing tissue-engineered solutions

These are exciting times in the field of plastic and reconstructive surgery. Meaningful advances in a wide range of basic science and clinical spheres have been made in the field in recent years, with direct translation to patient care. As a community, we are fortunate to be involved in such a vast, complex, increasingly interdisciplinary, rapidly expanding, and intellectually challenging field of surgery. Plastic surgery aims to restore “form and function” following a wide range of congenital or acquired defects, with procedures often transcending anatomic boundaries. This versatility promotes innovation, and with the recent advances in medical imaging (1), microsurgery (2), composite tissue allotransplantation (3, 4), nanotechnology (5), cell biology and biomaterials (6), and 3D printing (7), treatment options for patients are wider than ever before. For centuries, the “reconstructive ladder” was restricted to local flaps and skin grafts. Although these autologous options are reliable, plastic surgeons, with their constant wish to refine techniques, have become increasingly cognizant that there is the real potential for a paradigm shift in reconstructive surgery in the medium term. Tissue-engineered solutions (Figure 1A) offer the potential to alleviate the need for donor sites and their associated morbidity and to reduce hospital stay and associated costs (8).

Skin tissue engineering using 3D bioprinting: An evolving research field

BACKGROUND Commercially available tissue engineered skin remains elusive despite extensive research because the multi-stratified anisotropic structure is difficult to replicate in vitro using traditional tissue engineering techniques. Bioprinting, involving computer-controlled deposition of cells and scaffolds into spatially controlled patterns, is able to control not only the macro but also micro and nanoarchitecture and could offer the potential to more faithfully replicate native skin. METHODS We conducted a literature review using PubMed, EMBASE and Web of Science for studies on skin 3D bioprinting between 2009 and 2016, evaluating the bioprinting technique, cell source, scaffold type and in vitro and in vivo outcomes. RESULTS We outline the evolution of biological skin replacements, principles of bioprinting and how they apply to the skin tissue engineering field, potential clinical applications as well the current limitations and future avenues for research. Of the studies analysed, the most common types of bioinks consisted of keratinocytes and fibroblasts combined with collagen, although stem cells are gaining increasing recognition. Laser assisted deposition was the most common printing modality, although ink-jet and pneumatic extrusion have also been tested. Bioprinted skin promoted accelerated wound healing, was able to mimic stratified epidermis but not the thick, elastic, vascular dermis. CONCLUSIONS Although 3D bioprinting shows promise in engineering skin, evidenced by large collective investments from the cosmetic industry, the research is still in its infancy. The resolution, vascularity, optimal cell and scaffold combinations and cost of bioprinted skin are hurdles that need to be overcome before the clinical applicability can be realised. Small scale 3D skin tissue models for cosmetics, drug and toxicity testing as well as tumour modelling are likely to be translated first before we see this technology used in reconstructive surgery patients.

Tissue-Engineered Solutions in Plastic and Reconstructive Surgery: Principles and Practice

Recent advances in microsurgery, imaging, and transplantation have led to significant refinements in autologous reconstructive options; however, the morbidity of donor sites remains. This would be eliminated by successful clinical translation of tissue-engineered solutions into surgical practice. Plastic surgeons are uniquely placed to be intrinsically involved in the research and development of laboratory engineered tissues and their subsequent use. In this article, we present an overview of the field of tissue engineering, with the practicing plastic surgeon in mind. The Medical Research Council states that regenerative medicine and tissue engineering “holds the promise of revolutionizing patient care in the twenty-first century.” The UK government highlighted regenerative medicine as one of the key eight great technologies in their industrial strategy worthy of significant investment. The long-term aim of successful biomanufacture to repair composite defects depends on interdisciplinary collaboration between cell biologists, material scientists, engineers, and associated medical specialties; however currently, there is a current lack of coordination in the field as a whole. Barriers to translation are deep rooted at the basic science level, manifested by a lack of consensus on the ideal cell source, scaffold, molecular cues, and environment and manufacturing strategy. There is also insufficient understanding of the long-term safety and durability of tissue-engineered constructs. This review aims to highlight that individualized approaches to the field are not adequate, and research collaboratives will be essential to bring together differing areas of expertise to expedite future clinical translation. The use of tissue engineering in reconstructive surgery would result in a paradigm shift but it is important to maintain realistic expectations. It is generally accepted that it takes 20–30 years from the start of basic science research to clinical utility, demonstrated by contemporary treatments such as bone marrow transplantation. Although great advances have been made in the tissue engineering field, we highlight the barriers that need to be overcome before we see the routine use of tissue-engineered solutions.

Combining regenerative medicine strategies to provide durable reconstructive options: auricular cartilage tissue engineering

Recent advances in regenerative medicine place us in a unique position to improve the quality of engineered tissue. We use auricular cartilage as an exemplar to illustrate how the use of tissue-specific adult stem cells, assembly through additive manufacturing and improved understanding of postnatal tissue maturation will allow us to more accurately replicate native tissue anisotropy. This review highlights the limitations of autologous auricular reconstruction, including donor site morbidity, technical considerations and long-term complications. Current tissue-engineered auricular constructs implanted into immune-competent animal models have been observed to undergo inflammation, fibrosis, foreign body reaction, calcification and degradation. Combining biomimetic regenerative medicine strategies will allow us to improve tissue-engineered auricular cartilage with respect to biochemical composition and functionality, as well as microstructural organization and overall shape. Creating functional and durable tissue has the potential to shift the paradigm in reconstructive surgery by obviating the need for donor sites.

Long-Term Outcomes of Microsurgical Nasal Replantation: Review of the Literature and Illustrated 10-Year Follow-Up of a Pediatric Case with Full Sensory Recovery

We present a case of successful artery only total nose replantation in an 18-month-old child, with 10 years of follow-up and full sensory recovery despite no nerve repair. The common absence of veins for anastomosis does not prevent successful replant, as demonstrated with the use of Hirudo medicinalis use in this unique case. We comprehensively review the literature of this rare and complex injury and advocate microsurgical replantation where possible over other methods of nasal reconstruction.