Michael W. Findlay

Emerging Applications of Bedside 3D Printing in Plastic Surgery

Modern imaging techniques are an essential component of preoperative planning in plastic and reconstructive surgery. However, conventional modalities, including three-dimensional (3D) reconstructions, are limited by their representation on 2D workstations. 3D printing, also known as rapid prototyping or additive manufacturing, was once the province of industry to fabricate models from a computer-aided design (CAD) in a layer-by-layer manner. The early adopters in clinical practice have embraced the medical imaging-guided 3D-printed biomodels for their ability to provide tactile feedback and a superior appreciation of visuospatial relationship between anatomical structures. With increasing accessibility, investigators are able to convert standard imaging data into a CAD file using various 3D reconstruction softwares and ultimately fabricate 3D models using 3D printing techniques, such as stereolithography, multijet modeling, selective laser sintering, binder jet technique, and fused deposition modeling. However, many clinicians have questioned whether the cost-to-benefit ratio justifies its ongoing use. The cost and size of 3D printers have rapidly decreased over the past decade in parallel with the expiration of key 3D printing patents. Significant improvements in clinical imaging and user-friendly 3D software have permitted computer-aided 3D modeling of anatomical structures and implants without outsourcing in many cases. These developments offer immense potential for the application of 3D printing at the bedside for a variety of clinical applications. In this review, existing uses of 3D printing in plastic surgery practice spanning the spectrum from templates for facial transplantation surgery through to the formation of bespoke craniofacial implants to optimize post-operative esthetics are described. Furthermore, we discuss the potential of 3D printing to become an essential office-based tool in plastic surgery to assist in preoperative planning, developing intraoperative guidance tools, teaching patients and surgical trainees, and producing patient-specific prosthetics in everyday surgical practice.

Myogel, a novel, basement membrane-rich, extracellular matrix derived from skeletal muscle, is highly adipogenic in vivo and in vitro.

Background/Aims: Biological and synthetic scaffolds play important roles in tissue engineering and are being developed towards human clinical applications. Based on previous work from our laboratory, we propose that extracellular matrices from skeletal muscle could be developed for adipose tissue engineering. Methods: Extracellular matrices (Myogels) extracted from skeletal muscle of various species were assessed using biochemical assays including ELISA and Western blotting. Biofunctionality was assessed using an in vitro differentiation assay and a tissue engineering construct model in the rat. Results: Myogels were successfully extracted from mice, rats, pigs and humans. Myogels contained significant levels of laminin α4- and α2-subunits and collagen I compared to Matrigel™, which contains laminin 1 (α1β1γ1) and collagen IV. Levels of growth factors such as fibroblast growth factor 2 were significantly higher than Matrigel, vascular endothelial growth factor-A levels were significantly lower and all other growth factors were comparable. Myogels reproducibly stimulated adipogenic differentiation of preadipocytes in vitro and the growth of adipose tissue in the rat. Conclusions: We found Myogel induces adipocyte differentiation in vitroand shows strong adipogenic potential in vivo, inducing the growth of well-vascularised adipose tissue. Myogel offers an alternative for current support scaffolds in adipose tissue engineering, allowing the scaling up of animal models towards clinical adipose tissue engineering applications.

Tissue-Engineered Breast Reconstruction: Bridging the Gap toward Large-Volume Tissue Engineering in Humans

Background: Use of autologous tissue is ideal in breast reconstruction; however, insufficient donor tissue and surgical and donor-site morbidity all limit its use. Tissue engineering could provide replacement tissue, but only if vascularization of large tissue volumes is achievable. The authors sought to upscale their small-animal adipose tissue-engineering models to produce large volumes of tissue in a large animal (i.e., pig). Methods: Bilateral large-volume (78.5 ml) chambers were inserted subcutaneously in the groin enclosing a fat flap (5 ml) based on the superficial circumflex iliac pedicle for 6 (n = 4), 12 (n = 1), and 22 weeks (n = 2). Right chambers included a poly(L-lactide-co-glycolide) sponge. Other pedicle configurations, including a vascular pedicle alone (n = 2) or in combination with muscle (n = 2) or a free fat graft (n = 2), were investigated in preliminary studies. Serial assessment of tissue growth and vascularization by magnetic resonance imaging was undertaken during growth and correlated with quantitative histomorphometry at chamber removal. Results: All chambers filled with new tissue by 6 weeks, vascularized by the arteriovenous pedicle. In the fat flap chambers, the initial 5 ml of fat expanded to 25.9 ± 2.4, 39.4 ± 3.9, and 56.5 ml (by magnetic resonance imaging) at 6, 12, and 22 weeks, respectively. Adipose tissue volume was maintained up to 22 weeks after chamber removal (n = 2), including one where the specimen was transferred on its pedicle to an adjacent submammary pocket. Conclusion: The first clinically relevant volumes of tissue for in situ and remote breast reconstruction have been formed with implications for scaling of existing tissue-engineering models into human trials.

Vascularized tissue-engineered chambers promote survival and function of transplanted islets and improve glycemic control.

We have developed a chamber model of islet engraftment that optimizes islet survival by rapidly restoring islet‐extracellular matrix relationships and vascularization. Our aim was to assess the ability of syngeneic adult islets seeded into blood vessel‐containing chambers to correct streptozotocin‐induced diabetes in mice. Approximately 350 syngeneic islets suspended in Matrigel® extracellular matrix were inserted into chambers based on either the splenic or groin (epigastric) vascular beds, or, in the standard approach, injected under the renal capsule. Blood glucose was monitored weekly for 7 weeks, and an intraperitoneal glucose tolerance test performed at 6 weeks in the presence of the islet grafts. Relative to untreated diabetic animals, glycemic control significantly improved in all islet transplant groups, strongly correlating with islet counts in the graft (P<0.01), and with best results in the splenic chamber group. Glycemic control deteriorated after chambers were surgically removed at week 8. Immunohistochemistry revealed islets with abundant insulin content in grafts from all groups, but with significantly more islets in splenic chamber grafts than the other treatment groups (P<0.05). It is concluded that hyperglycemia in experimental type 1 diabetes can be effectively treated by islets seeded into a vascularized chamber functioning as a “pancreatic organoid.”

The regenerative role of adipose-derived stem cells (ADSC) in plastic and reconstructive surgery†

The potential use of stem cell‐based therapies for the repair and regeneration of various tissues and organs offers a paradigm shift in plastic and reconstructive surgery. The use of either embryonic stem cells (ESC) or induced pluripotent stem cells (iPSC) in clinical situations is limited because of regulations and ethical considerations even though these cells are theoretically highly beneficial. Adult mesenchymal stem cells appear to be an ideal stem cell population for practical regenerative medicine. Among these cells, adipose‐derived stem cells (ADSC) have the potential to differentiate the mesenchymal, ectodermal and endodermal lineages and are easy to harvest. Additionally, adipose tissue yields a high number of ADSC per volume of tissue. Based on this background knowledge, the purpose of this review is to summarise and describe the proliferation and differentiation capacities of ADSC together with current preclinical data regarding the use of ADSC as regenerative tools in plastic and reconstructive surgery.

Long-term persistence of tissue-engineered adipose flaps in a murine model to 1 year: an update.

Background: Tissue engineering of patient-specific adipose tissue has the potential to revolutionize reconstructive surgery. Numerous models have been described for the production of adipose tissue with success in the short term, but little has been reported on the stability of this tissue-engineered fat beyond 4 months. Methods: A murine model of de novo adipogenesis producing a potentially transplantable adipose tissue flap within 4 to 6 weeks was developed in the authors’ laboratory. In this study, the authors assess the ability of three-chamber (44-&mgr;l volume) configurations shown to be adipogenic in previous short-term studies (autograft, n = 8; open, n = 6; fat flap, n = 11) to maintain their tissue volume for up to 12 months in vivo, to determine the most adipogenic configuration in the long term. Results: Those chambers having the most contact with existing vascularized adipose tissue (open and fat flap groups) showed increased mean adipose tissue percentage (77 ± 5.6 percent and 81 ± 6.9 percent, respectively; p < 0.0007) and volume (12 ± 6.8 &mgr;l and 30 ± 14 &mgr;l, respectively; p < 0.025) when compared with short-term controls and greater adipose tissue volume than the autograft (sealed) chamber group (4.9 ± 5.8 &mgr;l; p = 0.0001) at 1 year. Inclusion of a vascularized fat flap within the chamber produced the best results, with new fat completely filling the chamber by 1 year. Conclusions: These findings demonstrate that fat produced by tissue engineering is capable of maintaining its volume when the appropriate microenvironment is provided. This has important implications for the application of tissue-engineering techniques in humans.

Early return to work and improved range of motion with modified relative motion splinting: a retrospective comparison with immobilization splinting for zones V and VI extensor tendon repairs:

Introduction There is a lack of evidence on the best method for rehabilitating extensor tendon injuries in zones V and VI. The purpose of this study was to evaluate the outcomes of modified relative motion splinting compared with immobilization following repair of extensor tendons in zones V and VI. Methods A retrospective analysis compared the outcomes of relative motion splinting with immobilization. Sixteen patients (16 fingers) were treated by conventional immobilization splinting for four weeks (immobilization group) followed by mobilization with avoidance of ‘at-risk/heavy’ activities for a further 4–6 weeks. Twenty-three patients (23 fingers) were treated with the modified relative motion splint (mRMS group) during the day and a resting splint worn overnight for the first four weeks. The relative motion splint was continued for ‘at-risk/heavy’ activities for a further 4–6 weeks. Results The mRMS group demonstrated statistically significant improvement in range of motion compared with the immobilization group. This effect was most marked at six weeks (P = 0.0194, two-way mixed ANOVA) with the mRMS group achieving a 12% higher mean percentage total active motion (P = 0.0076, Mann-Whitney U test). Results were similar for both groups 12 weeks postoperatively. Differences in return to work times between groups were statistically significant (P = 0.0062, Mann-Whitney U test). Average return to work was 9.4 weeks for the immobilization group and 3.3 weeks for the mRMS group, equating to a 42 days earlier return to work for the mRMS group. There was no incidence of tendon rupture in either group. Conclusion This study demonstrates that modified relative motion splintage (finger based without wrist component) can be applied in the postoperative management of single zone V or VI extensor tendon repairs. The main advantages of this protocol, compared with immobilization include the small simple splint design, and straightforward patient instructions that enable earlier mobilization, functional hand use and return to both daily living and work.

Development and evaluation of elastomeric hollow fiber membranes as small diameter vascular graft substitutes

Engineering of small diameter (<6mm) vascular grafts (SDVGs) for clinical use remains a significant challenge. Here, elastomeric polyester urethane (PEU)-based hollow fiber membranes (HFMs) are presented as an SDVG candidate to target the limitations of current technologies and improve tissue engineering designs. HFMs are fabricated by a simple phase inversion method. HFM dimensions are tailored through adjustments to fabrication parameters. The walls of HFMs are highly porous. The HFMs are very elastic, with moduli ranging from 1-4MPa, strengths from 1-5MPa, and max strains from 300-500%. Permeability of the HFMs varies from 0.5-3.5×10(-6)cm/s, while burst pressure varies from 25 to 35psi. The suture retention forces of HFMs are in the range of 0.8 to 1.2N. These properties match those of blood vessels. A slow degradation profile is observed for all HFMs, with 71 to 78% of the original mass remaining after 8weeks, providing a suitable profile for potential cellular incorporation and tissue replacement. Both human endothelial cells and human mesenchymal stem cells proliferate well in the presence of HFMs up to 7days. These results demonstrate a promising customizable PEU HFMs for small diameter vascular repair and tissue engineering applications.

The cervico-submental keystone island flap for locoregional head and neck reconstruction

BACKGROUND Locally advanced head and neck cancer often requires wide resections of the cheek and parotid gland, and in an ageing population preferred reconstructive options aim to avoid lengthy operating times or high risk surgery. While most large parotid defects traditionally require free flap reconstruction, we describe a new and versatile locoregional flap that has been shown to be reliable, simple and safe. METHODS We describe the cervico-submental (CSM) keystone-design perforator island flap for head and neck reconstruction, including an analysis of 33 consecutive patients with a range of head and neck defects. The flap was raised based on perforators of the external carotid artery and its branches, and designed to overlay the C2/C3 dermatomes (an aide memoire for flap design). The indications, and surgical technique are described. RESULTS In 33 consecutive patients, no major complications were encountered. Five patients developed superficial infections, one developed post-operative bleeding and one patient developed partial tip necrosis. Theatre time was considerably shorter than our alternative reconstructive options. CONCLUSION The CSM keystone-design perforator island flap is a novel and versatile flap, which can be used in a range of advanced cheek and parotidectomy defects, and may enable improved surgical management in an increasingly elderly and high-risk population.

Keystone island flap reconstruction of parotid defects.

Background: Skin cancers of the face and scalp have a propensity to metastasize to the parotid group of lymph nodes. The resection of these secondary tumors and other primary tumors in the parotid region often results in defects requiring flap reconstruction. Pectoralis major flaps are reliable and free flaps are arguably the criterion standard. However, we have found keystone island flaps to be a simple and robust alternative, with low donor-site and patient morbidity. The aim of this article is to share our surgical technique, experience, and outcomes of reconstructing parotid defects with keystone island flaps. Methods: The authors retrospectively reviewed 62 patients who had 63 parotid defect reconstructions at a single institution from 2004 to 2009 (5-year period). Results: The diseases involved were squamous cell carcinoma (52 cases), melanoma (five cases), basal cell carcinoma (four cases), and others (two cases). Nine patients presented with a previous history of radiotherapy and 33 patients required adjuvant radiotherapy. Seven patients (11 percent) suffered postoperative complications necessitating a return to the operating room. Conclusions: Keystone island perforator-based flaps present an alternative to free tissue transfer. From the series presented, it can be seen that reliable and reproducible results are achievable. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.