Elisabeth K. Beahm

Progress in adipose tissue construct development

Although the field of tissue engineering has been the focus of a great deal of promise and study, only recently has significant attention been given to the engineering of soft tissues. The applicability of an engineered adipose construct as a basic science model and a reconstructive tool is unquestioned; yet, there have been limitations in previous work, specifically issues of construct size and maintenance over time. This article briefly overviews the pivotal factors necessary for adipocyte growth and differentiation, optimal scaffolds for the engineering of soft tissues, and a means of providing vascular support for these highly demanding cells. Clinical science and bioengineering concepts that may provide the foundation toward the successful in vivo engineering of an adipose tissue construct that maintains its complex three-dimensional shape over time are critically reviewed.

Auricular reconstruction for microtia: Part II. Surgical techniques

Reconstruction of the microtic ear represents one of the most demanding challenges in reconstructive surgery. In this review the two most commonly used techniques for ear reconstruction, the Brent and Nagata techniques, are addressed in detail. Unique to this endeavor, the originator of each technique has been allowed to submit representative case material and to address the pros and cons of the others technique. What follows is a detailed, insightful overview of microtia reconstruction, as a state of the art. The review then details commonly encountered problems in ear reconstruction and pertinent technical points. Finally, a glimpse into the future is offered with an accounting of the advances made in tissue engineering as this technology applies to auricular reconstruction.

The advantages of free abdominal-based flaps over implants for breast reconstruction in obese patients

Background: The authors hypothesized that, for obese patients, delayed abdominal-based free flap (rather than implant-based and immediate) breast reconstruction would result in fewer overall complications and reconstruction losses. Methods: The authors retrospectively analyzed consecutive implant- and abdominal-based free flap breast reconstructions performed in obese patients between 2005 and 2010 by utilizing the World Health Organization obesity classifications: class I, 30.0 to 34.9 kg/m2; class II, 35.0 to 39.9 kg/m2; and class III, ≥40 kg/m2. Primary outcome measures included flap failures and overall complications. Logistic regression analysis identified associations among patient, defect, and reconstructive characteristics and surgical outcomes. Results: The analysis included 990 breast reconstructions (548 flaps versus 442 implants) in 700 patients. Mean follow-up was 17 months. Age, smoking, medical illness, and body mass index greater than 37 predicted overall complications on regression analysis. Implants demonstrated a higher failure rate (15.8 percent) than flaps (1.5 percent). Although failure rates were similar for immediate and delayed flap reconstructions overall (1.3 versus 1.9 percent) and among obesity classifications, there was a trend toward more implant failures in immediate rather than delayed reconstructions (16.8 versus 5.3 percent). Differences between immediate implant versus flap reconstruction failure rates were highest among more obese patients [class II (24.7 versus 1.3 percent) and class III (25.4 versus 0 percent) compared with class I (11.7 versus 1.4 percent)]. Conclusions: Obese patients (particularly class II and III) experience higher failure rates with implant-based breast reconstruction, particularly immediate reconstruction. Free flap techniques or delayed implant reconstruction may be warranted in this population. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Auricular reconstruction for microtia: part I. Anatomy, embryology, and clinical evaluation.

Learning Objectives: After studying this article, the participant should be able to: (1) Understand external ear anatomy and embryology. (2) Develop an approach to evaluation of microtia, including otologic considerations.

Microsurgical replantation of the lip: a multi-institutional experience.

&NA; Traumatic amputation of the lip is a rare yet devastating event affecting both form and function. Considering the available methods for reconstruction, replantation may offer a reasonable solution. We sought to characterize the variables associated with lip replantation and to assess the outcome in a retrospective review of 13 lip replantations performed in 12 institutions utilizing a form database and clinical and photographic analysis. Lip replantation was successful in all 13 patients; partial flap loss occurred in one patient owing to iatrogenic injury. Follow‐up averaged 3.1 years. Average patient age at the time of injury was 21.1 years. There were six male and seven female patients. Injuries in two patients were the result of a human bite, the remaining injuries resulted from dog bites. One patient had significant associated injuries. Average length of hospital stay was 11.9 days. Ten patients suffered amputations of the upper lip, and three suffered amputations of the lower lip. Average defect size was 10.6 cm2. Operative time averaged 5.7 hours (range 2.5 to 12 hours). Warm ischemia time averaged 2.9 hours, and cold ischemia time averaged 2.7 hours. Donor and recipient veins were often scarce; all patients had at least one arterial anastomosis, whereas no vein was available in 7 of 13 patients; vein grafts were required in one patient. Leech therapy was employed in 11 of 13 patients. Anticoagulant therapy was administered in the majority of patients. Systemic heparin was utilized in 10 of 13 patients, low molecular weight dextran was used in 7 of 13 patients, and aspirin was given to 7 of 13 patients. One bleeding complication was incurred. An average of 6.2 units of packed red blood cells was administered to 12 of 13 patients (adjusted to 250 cc/unit). Antispasmodic therapy was employed in six of eight patients intraoperatively and in two of eight patients postoperatively. Intraoperative complications included difficulty identifying veins in 7 of 13 patients, arterial spasm in 1 of 13 patients, and vessel diameter <0.5 mm in 4 patients. Postoperatively, one patient suffered vein thrombosis requiring anastomotic revision. Broad spectrum antibiotics were administered to all patients, and there were no infections. Nearly onethird (4 of 13) patients suffered prolonged edema lasting >4 months. Color match of the replanted lip segment was rated excellent in all cases. Hypertrophic scarring occurred in 6 of 13 patients. A total of 12 revision procedures was performed in six patients. Interestingly, leech therapy resulted in permanent visible scarring as a result of the leech bite in 6 of 11 patients treated. Ten patients demonstrated active orbicularis muscle contraction in the replanted lip segment. Stomal continence was present in all lips. Sensibility return in the replanted lip segment was quite good with 12 of 13 patients demonstrating at least protective moving two‐point sensibility (≥10 mm). Partial replant necrosis in one patient resulted in significant scar and contraction that compromised the aesthetic appearance. Overall, however, all patients were uniformly pleased with their final results. This clinical study is one of the largest of its kind on lip replantation. Although this represents a multi‐institutional experience, the data are remarkably consistent. Re‐establishment of venous outflow seems to be the most problematic technical challenge. By incorporating the adjuncts of anticoagulation, leech therapy, and antispasmodics, a successful outcome can be expected despite the paucity of vessels and small vessel size. The risks of blood transfusion, lengthy operative time, and hospital stay must be weighed against the functional benefits. (Plast. Reconstr. Surg. 102: 358, 1998.)

Combining decellularized human adipose tissue extracellular matrix and adipose-derived stem cells for adipose tissue engineering

Repair of soft tissue defects resulting from lumpectomy or mastectomy has become an important rehabilitation process for breast cancer patients. This study aimed to provide an adipose tissue engineering platform for soft tissue defect repair by combining decellularized human adipose tissue extracellular matrix (hDAM) and human adipose-derived stem cells (hASCs). To derive hDAM incised human adipose tissues underwent a decellularization process. Effective cell removal and lipid removal were proved by immunohistochemical analysis and DNA quantification. Scanning electron microscopic examination showed a three-dimensional nanofibrous architecture in hDAM. The hDAM included collagen, sulfated glycosaminoglycan, and vascular endothelial growth factor, but lacked major histocompatibility complex antigen I. hASC viability and proliferation on hDAM were proven in vitro. hDAM implanted subcutaneously in Fischer rats did not cause an immunogenic response, and it underwent remodeling, as indicated by host cell infiltration, neovascularization, and adipose tissue formation. Fresh fat grafts (Coleman technique) and engineered fat grafts (hDAM combined with hASCs) were implanted subcutaneously in nude rats. The implanted engineered fat grafts maintained their volume for 8 weeks, and the hASCs contributed to adipose tissue formation. In summary, the combination of hDAM and hASCs provides not only a clinically translatable platform for adipose tissue engineering, but also a vehicle for elucidating fat grafting mechanisms.

Assessment of Breast Aesthetics

Summary: A good aesthetic outcome is an important endpoint of breast cancer treatment. Subjective ratings, direct physical measurements, measurements on photographs, and assessment by three-dimensional imaging are reviewed and future directions in aesthetic outcome measurements are discussed. Qualitative, subjective scales have frequently been used to assess aesthetic outcomes following breast cancer treatment. However, none of these scales has achieved widespread use because they are typically vague and have low intraobserver and interobserver agreement. Anthropometry is not routinely performed because conducting the large studies needed to validate anthropometric measures (i.e., studies in which several observers measure the same subjects multiple times) is impractical. Quantitative measures based on digital/digitized photographs have yielded acceptable results but have some limitations. Three-dimensional imaging has the potential to enable consistent, objective assessment of breast appearance, including properties (e.g., volume) that are not available from two-dimensional images. However, further work is needed to define three-dimensional measures of aesthetic properties and how they should be interpreted.

The efficacy of bilateral lower abdominal free flaps for unilateral breast reconstruction.

Background: In large-breasted women, those with midline abdominal scars, or those with scant abdominal tissue, a unipedicled lower abdominal flap may be insufficient for breast reconstruction. In these circumstances, bipedicled flaps may best satisfy the reconstructive requirements, but outcomes with bilateral free flaps for unilateral breast reconstruction are generally lacking. Methods: A retrospective review of patients in whom two vascular pedicles/flaps were used to simultaneously reconstruct a single breast was used to assess operative outcomes. Results: Forty patients (80 flaps) for whom two free tissue transfers were used to simultaneously reconstruct a single breast were identified. The majority of patients had a native breast cup size of C or larger. The flaps used included the superficial inferior epigastric artery (SIEA) flap (n = 29; 36 percent), the transverse rectus abdominis musculocutaneous (TRAM) flap (n = 9; 11 percent), the muscle-sparing TRAM flap (n = 15; 19 percent), and the deep inferior epigastric perforator (DIEP) flap (n = 27; 34 percent). Flaps were paired in a variety of configurations, most commonly using a muscle-sparing TRAM flap in conjunction with a DIEP flap or an SIEA flap. Recipient vessels included a combination of the internal mammary and thoracodorsal vessels and the pedicles of combined flaps (turbocharged). There were no flap losses. Two flaps required reexploration for microsurgical anastomotic revision, and both were successfully salvaged. Isolated fat necrosis was encountered in only three of 80 flaps. Conclusions: This study suggests that bilateral, bipedicled, abdominal free flaps for unilateral breast reconstruction can be used safely with a high degree of success. These combined flaps provide for enhanced vascular perfusion of the lower abdominal flap territory, allowing for harvest of larger volumes of tissue for reconstruction.

Animal models for adipose tissue engineering.

There is a critical need for adequate reconstruction of soft tissue defects resulting from tumor resection, trauma, and congenital abnormalities. To be sure, adipose tissue engineering strategies offer promising solutions. However, before clinical translation can occur, efficacy must be proven in animal studies. The aim of this review is to provide an overview of animal models currently employed for adipose tissue engineering.

Engineering vascularized soft tissue flaps in an animal model using human adipose-derived stem cells and VEGF+PLGA/PEG microspheres on a collagen-chitosan scaffold with a flow-through vascular pedicle

Insufficient neovascularization is associated with high levels of resorption and necrosis in autologous and engineered fat grafts. We tested the hypothesis that incorporating angiogenic growth factor into a scaffold-stem cell construct and implanting this construct around a vascular pedicle improves neovascularization and adipogenesis for engineering soft tissue flaps. Poly(lactic-co-glycolic-acid/polyethylene glycol (PLGA/PEG) microspheres containing vascular endothelial growth factor (VEGF) were impregnated into collagen-chitosan scaffolds seeded with human adipose-derived stem cells (hASCs). This setup was analyzed in vitro and then implanted into isolated chambers around a discrete vascular pedicle in nude rats. Engineered tissue samples within the chambers were harvested and analyzed for differences in vascularization and adipose tissue growth. In vitro testing showed that the collagen-chitosan scaffold provided a supportive environment for hASC integration and proliferation. PLGA/PEG microspheres with slow-release VEGF had no negative effect on cell survival in collagen-chitosan scaffolds. In vivo, the system resulted in a statistically significant increase in neovascularization that in turn led to a significant increase in adipose tissue persistence after 8 weeks versus control constructs. These data indicate that our model-hASCs integrated with a collagen-chitosan scaffold incorporated with VEGF-containing PLGA/PEG microspheres supported by a predominant vascular vessel inside a chamber-provides a promising, clinically translatable platform for engineering vascularized soft tissue flap. The engineered adipose tissue with a vascular pedicle could conceivably be transferred as a vascularized soft tissue pedicle flap or free flap to a recipient site for the repair of soft-tissue defects.