Melvin Spira

Increased free fat-graft survival with the long-term, local delivery of insulin, insulin-like growth factor-I, and basic fibroblast growth factor by PLGA/PEG microspheres.

&NA; The present investigation evaluates the effects of longterm, local delivery of insulin, insulin‐like growth factor‐1 (IGF‐1), and basic fibroblast growth factor (bFGF) on fatgraft survival using a poly (lactic‐co‐glycolic‐acid)‐polyethylene glycol (PLGA/PEG) microsphere delivery system. Twelve‐micrometer PLGA/PEG microspheres incorporated separately with insulin, IGF‐1, and bFGF were manufactured using a double‐emulsion solvent‐extraction technique. Inguinal fat from Sprague Dawley rats was harvested, diced, washed, and mixed with (1) insulin microspheres, (2) insulin‐like growth factor‐1 microspheres, (3) basic fibroblast growth factor microspheres, (4) a combination of the insulin and IGF‐1 microspheres, and (5) a combination of insulin, IGF‐1, and bFGF microspheres. The treated fat grafts were implanted autologously into subdermal pockets in six animals for each group. Animals receiving untreated fat grafts and fat grafts treated with blank microspheres constituted two external control groups (six animals per external control group). At 12 weeks, all fat‐graft groups were compared on the basis of weight maintenance and a histomorphometric analysis of adipocyte area percentage, indices of volume retention and cell composition, respectively. Weight maintenance was defined as the final graft weight as a percent of the implanted graft weight. All growth factor treatments significantly increased fat‐graft weight maintenance objectively, and volume maintenance grossly, in comparison with the untreated and blank microsphere‐treated controls. Treatment with insulin and IGF‐1, alone or in combination, was found to increase the adipocyte area percentage in comparison with fat grafts treated with bFGF alone or in combination with other growth factors. In conclusion, the findings of this study indicate that long‐term, local delivery of growth factors with PLGA/PEG microspheres has the potential to increase fat‐graft survival rates. Further, the type of growth factor delivered may influence the cellular/stromal composition of the grafted tissue. (Plast. Reconstr. Surg. 105: 1712, 2000.)

De novo adipose tissue generation through long-term, local delivery of insulin and insulin-like growth factor-1 by PLGA/PEG microspheres in an in vivo rat model: A novel concept and capability

&NA; This study was undertaken to characterize the duration of long‐term growth factor delivery by poly(lactic‐co‐glycolicacid)‐polyethylene glycol (PLGA/PEG) microspheres and to evaluate the potential of long‐term delivery of insulin and insulin‐like growth factor‐1 (IGF‐1) for the de novo generation of adipose tissue in vivo. PLGA/PEG microspheres containing insulin and IGF‐1, separately, were produced by a double‐emulsion solvent‐extraction technique. In the first phase of the experiment, the in vitro release kinetics of the microspheres were evaluated for the optical density and polyacrylamide gel electrophoresis of solutions incubated with insulin‐containing microspheres for four different periods of time (n = 1). The finding of increased concentrations of soluble insulin with increased incubation time confirmed continual protein release. In the second stage of the experiment, 16 rats were divided equally into four study groups (insulin, IGF‐1, insulin + IGF‐1, and blank microspheres) (n = 4). Insulin and IGF‐1 containing microspheres were administered directly to the deep muscular fascia of the rat abdominal wall to evaluate the potential for de novo adipose tissue generation via adipogenic differentiation from native nonadipocyte cell pools in vivo. Animals treated with blank microspheres served as an external control group. At the 4‐week harvest period, multiple ectopic islands of adipose tissue were observed on the abdominal wall of the animals treated with insulin, IGF‐1, and insulin + IGF‐1 microspheres. Such islands were not seen in the blank micro sphere group. Hematoxylin and eosin‐stained sections of the growth factor groups demonstrated mature adipocytes interspersed with fibrous tissue superficial to the abdominal wall musculature and continuous with the fascia. Oil‐Red‐O stained sections demonstrated that these cells contained lipid. Computer‐aided image analysis of histologic sections confirmed that there were statistically significant increases in the amount of “ectopic” adipose neotissue developed on the abdominal wall of animals treated with growth factor microspheres. In conclusion, this study confirms the long‐term release of proteins from PLGA/PEG microspheres up to 4 weeks and demonstrates the potential of long‐term local insulin and IGF‐1 to induce adipogenic differentiation to mature lipid‐containing adipocytes from nonadipocyte cell pools in vivo at 4 weeks. (Plast. Reconstr. Surg. 105: 1721, 2000.)

New Capillary Bed Formation with a Surgically Constructed Arteriovenous Fistula

This study on 24 rats has demonstrated that neovascularization of the skin through an arteriovenous fistula is possible. A vascular bed can be created by the use of long interpositional vein grafts. An arteriovenous fistula in the shape of a loop could not only provide vascularity to create a skin flap of unlimited size but could possibly vascularize a digital replantation with severely damaged vessels and provide enough additional vascularity to facilitate the take of bone grafts and tissue composites.

Study of the delay phenomenon in the rat TRAM flap model.

Partial flap necrosis is frequently associated with the pedicled TRAM flap in the clinical setting. We created a TRAM flap model in rats (one control group and four delay groups; n = 8 in each group) and used a variety of flap delay techniques and vascular manipulations in an effort to increase the surviving area of the flap. The areas of surviving skin paddles in the five groups ranged from 4.4 cm2 in the control group to 9.9 cm2 in one of the delay groups. Analysis of variance and Tukeys pairwise comparisons indicated that delay groups II, III, and IV differed significantly from the control group (ANOVA F = 15.99, p < 0.001; Tukey experimental ER = 0.05, individual ER = 0.0068; critical value = 4.07). Ligation of the superficial inferior epigastric vessels and deep superior epigastric vessels (dominant pedicle) 1 week before TRAM flap surgery increased the area of survival of the skin paddle significantly in the rat model. The procedure is relatively easy to perform, and our laboratory findings should be readily reproducible in clinical practice.

Prefabricated flaps : experimental and clinical review

Prefabricated flaps are a useful tool for the reconstructive surgeon and present a number of advantages: 1. Specific preferred tissue composites, regardless of their native vascular origin, can be transferred as free or pedicled flaps. 2. Larger flaps of specialized tissue may be transferred safely. 3. Donor-site morbidity is reduced. 4. The functional outcome for the patients may be more satisfactory. The various methods of flap prefabrication include vascular induction through stage transfer; pretransfer delay, expansion, and grafting; the use of alloplastic materials; and tissue bioengineering. We have reviewed both the experimental and clinical research on flap prefabrication, describing the theory, technique, and advantages of each method.

Salvage of amputation stumps by secondary reconstruction utilizing microsurgical free-tissue transfer.

During a 2-year period, 15 lower and upper extremity amputees were treated by microsurgical free-tissue transfer in an effort to salvage their amputation stumps. Salvage of length and restoration of contour to aid in prosthetic rehabilitation were the two main indications for reconstruction. Included in the 15 transfers were 3 scapular free flaps, 11 latissimus dorsi musculocutaneous flaps, and 1 groin flap. Thirteen of the patients in this group were refitted with prostheses following reconstruction and did well with no pain or skin breakdown of the resurfaced stumps. The follow-up period on these patients averaged 16 months. One patient, in whom the flap succeeded, underwent stump soft-tissue revision and myodesis. One patient, in whom the flap failed, continued to develop recurrent ulceration in his stump. This clinical experience followed an extensive laboratory study of 12 above-knee amputation patients using noninvasive Doppler ultrasound measurements to determine weight-loading and interface-pressure distribution between the stump and the socket of the prostheses and their relation to stump length and circumference.

A mastopexy technique for mild to moderate ptosis.

A surgical technique for mastopexy, done through a circumareolar incision and leaving no noticeable scar, is described. The skin brassiere is undermined and a rotation-invagination and suture maneuver are performed which simultaneously augments the projection of the breast and elevates the nipple-areola complex. The overlying skin contours itself to the reshaped breast. The favorable results obtained in six patients with this new method are encouraging and further use in selected patients is planned.

Otoplasty: what I do now--a 30-year perspective.

The author presents his otoplasty technique, a variation on Mustardés original procedure, which he has used for more than 30 years in more than 200 otoplasties. Timing, indications, and photographic documentation are discussed, and the operative procedure, including the preoperative work-up and anesthesia, is described in step-by-step detail. Postoperative care and early and late complications, from infection to the dissatisfied patient, are discussed extensively.

Development of a TRAM flap model in the rat and study of vascular dominance

To investigate the suitability of the rat TRAM flap model for human TRAM flap research, we designed four different TRAM flaps with 10 X 3 cm rectangular skin paddles in rats: type 1 (n = 6), superior TRAM flap with unilateral superior rectus muscle pedicle; type 2 (n = 6), superior TRAM flap with unilateral inferior rectus muscle pedicle; type 3 (n = 6), inferior TRAM flap with unilateral superior rectus muscle pedicle; and type 4 (n = 6), inferior TRAM flap with unilateral inferior rectus muscle pedicle. We elevated and sutured back the TRAM flaps and measured the survival skin paddle areas. Our study demonstrated that in the rat TRAM flap model, the superior deep epigastric vessels are a more important source of vascularity for the skin paddle than the inferior deep epigastric vessels. A 5-cm lateral extension from the midvertical line was enough to cause some distal necrosis in every flap. A cephalically placed, inferiorly pedicled rat TRAM flap (type 2) has the smallest area of skin paddle survival; we concluded, therefore, that this flap placement is the most suitable for TRAM flap research.

Cartilage warping: an experimental model.

Cadaveric cartilage was cut into blocks with a newly devised cartilage cutter. Over one-hundred pieces of cartilage were used to define a kinetics curve of cartilage warping. Kinetics curves were developed for a control group of cartilage blocks placed in saline-soaked gauze (n = 46). In addition, kinetics curves were developed for cartilage placed in hypotonic saline (n = 14), hypertonic saline (n = 14), and cyanoacrylate glue (n = 6). Photographs of all groups were taken at timed intervals in order to plot the cartilage warping. It was found that pieces of cartilage which were cut peripherally (n = 6) warped twice as much as those cut centrally (n = 40). This was significant to p = 0.001. Within 15 minutes, centrally cut pieces of cartilage warped to approximately 90 percent of their end warpage; on the other hand, peripherally cut pieces of cartilage required 30 minutes to warp 90 percent of their destined warpage. The variables used did not significantly alter the kinetics curves as compared with control.