Keith T. Paige

Transplantation of chondrocytes utilizing a polymer-cell construct to produce tissue-engineered cartilage in the shape of a human ear

&NA; This study evaluates the feasibility of growing tissue‐engineered cartilage in the shape of a human ear using chondrocytes seeded onto a synthetic biodegradable polymer fashioned in the shape of a 3‐year‐old childs auricle. A polymer template was formed in the shape of a human auricle using a nonwoven mesh of polyglycolic acid molded after being immersed in a 1% solution of polylactic acid. Each polyglycolic acid‐polylactic acid template was seeded with chondrocytes isolated from bovine articular cartilage and then implanted into subcutaneous pockets on the dorsa of 10 athymic mice. The three‐dimensional structure was well maintained after removal of an external stent that had been applied for 4 weeks. Specimens harvested 12 weeks after implantation and subjected to gross morphologic and histologic analysis demonstrated new cartilage formation. The overall geometry of the experimental specimens closely resembled the complex structure of the childs auricle. These findings demonstrate that polyglycolic acid‐polylactic acid constructs can be fabricated in a very intricate configuration and seeded with chondrocytes to generate new cartilage that would be useful in plastic and reconstructive surgery. (Plast. Reconstr. Surg. 100: 297, 1997.)

Endoscopic treatment of vesicoureteral reflux with a chondrocyte-alginate suspension

Injection of polytetrafluoroethylene (Teflon) or collagen has been used in the endoscopic treatment of vesicoureteral reflux. Although the principle of an endoscopic treatment is valid, there are concerns regarding the long-term safety and effectiveness of these substances. In search of a different injectable material we conducted experiments using chondrocytes in a biodegradable polymer solution for the treatment of vesicoureteral reflux in an animal model. Reflux was created in 4 mini-pigs and confirmed with a cystogram. Cartilage was obtained from the auricular surface of each animal. Chondrocytes were harvested and expanded in vitro. The cells were individually quantitated and concentrated to 40 million cells per cc. The cell suspensions were mixed with a sodium alginate and calcium sulfate solution. Each pig was injected unilaterally in the subureteral region with the autologous chondrocyte suspension. The opposite ureter served as an internal control in all animals. Cystograms showed resolution of reflux in the treated side and persistence of reflux in the opposite untreated side in each instance. Excretory urograms revealed no evidence of obstruction. Histological examination of the subureteral region demonstrated cartilage. Autologous chondrocytes can be readily harvested, expanded in vitro and injected cystoscopically. The cells survive and form a cartilage nidus that is nonantigenic. This system is able to correct reflux without any evidence of obstruction.

Injectable Alginate Seeded with Chondrocytes as a Potential Treatment for Vesicoureteral Reflux

Injection of polytetrafluoroethylene (Teflon) or collagen has been used in the endoscopic treatment of vesicoureteral reflux. Although the principle of an endoscopic treatment is valid, there are concerns regarding the long-term safety and effectiveness of these substances. The goal of several investigators has been to find alternate implant materials that would be safe for human use. Toward this goal we conducted a study to determine the effect of chondrocytes using a biodegradable polymer solution as a template. Hyaline cartilage was obtained from the articular surfaces of calf shoulders and chondrocytes were harvested. Chondrocyte suspensions were concentrated to 20, 30 and 40 x 10(6) cells per cc and mixed with dry alginate powder (a biodegradable polymer) to form a gel. Twelve athymic mice were injected subcutaneously with a chondrocyte-alginate solution. Each mouse had 4 injection sites, consisting of control, 10, 15 and 20 x 10(6) chondrocyte cells (48 injection sites). Mice were sacrificed at 2, 4, 6 and 12 weeks after injection. Histological examination of the injection sites demonstrated evidence of cartilage formation in 34 of the 36 experimental injection sites. Gross examination of the injection sites with increasing time showed that the polymer gels were progressively replaced by cartilage. The ultimate size of the cartilage formed was related to the initial chondrocyte concentration injected, and appeared to be uniform and stable within each category. There was no evidence of cartilage formation in the 12 controls. Histological analyses of distant organs showed no evidence of cartilage or alginate gel migration, or granuloma formation. In conclusion, chondrocyte-alginate gel suspensions are injectable, appear to be nonmigratory and are able to conserve their volume. In addition, the use of autologous cartilage cells would preclude an immunological reaction. These preliminary studies indicate that autologous cartilage-polymer gel solutions may be potentially useful in the endoscopic treatment of reflux.

De novo cartilage generation using calcium alginate-chondrocyte constructs.

&NA; These studies investigated the utility of calcium alginate as a biocompatible polymer matrix within which large numbers of chondrocytes could be held successfully in a three‐dimensional structure and implanted. Further, the ability of chondrocyte‐calcium alginate constructs to engraft and generate new cartilage was examined. Chondrocytes isolated from calf shoulders were mixed with a 1.5% sodium alginate solution to generate cell suspensions with densities of 0, 1.0, 5.0, and 10.0 × 106 chondrocytes/ml. The cell suspensions were gelled to create disks that were placed in subcutaneous pockets on the dorsums of nude mice. The alginate concentration and CaCl2 concentration used to make the disks also were varied. A total of 20 mice were implanted with 67 bovine chondrocyte‐calcium alginate constructs. Samples with an initial cellular density of at least 5.0 × 106 chondrocytes/ml demonstrated gross cartilage formation 12 weeks alter implantation. Cartilage formation was observed microscopically in specimens with a cellular density as low as 1.0 × 106 chondrocytes/ ml. The histoarchitecture of the new cartilage closely resembled that of native cartilage. Cartilage formation was independent of CaCl2 concentration (15 to 100 mM) or alginate concentration (0.5% to 4.0%) used in gel polymerization. (Plast. Reamslr. Surg. 97: 168, 1996.)

Experimental tracheal replacement using tissue-engineered cartilage

The authors tested the feasibility of using tissue-engineered cartilage, grown in the shape of cylinders, for replacing large circumferential defects of the cervical trachea in rats. Chondrocytes obtained from the shoulder of newborn calves were seeded onto a synthetic nonwoven mesh, 100 microns thick, of polyglycolic acid fibers 15 microns in diameter, cut into pieces of 2.5 x 4 cm. Twenty cell-polymer constructs were wrapped around silastic tubes and implanted into 10 nude mice for 4 weeks. Specimens were then excised and evaluated grossly and histologically for the presence of new cartilage, and biomechanically for their ability to resist collapse upon application of negative pressure. Six cylinders of tissue-engineered cartilage were then sutured into large circumferential defects created in the cervical tracheas of nude rats to replace the excised trachea. Implantation of cell-polymer constructs resulted in the formation of cylinders of hyaline cartilage. When placed within the lumen of a segment of bowel denuded of its mucosal lining, the hollow cylinders resisted collapse in all instances upon administration of negative 200 mm Hg pressure. The cartilage was grossly and histologically identical to that from which the cells had been initially isolated. Four of the six animals receiving these cartilage cylinders as tracheal replacements survived the procedure and were able to breathe in an unassisted fashion. Three of these animals never recovered fully from the anesthetic and the operation, and expired at 24, 48, and 72 hours. The fourth animal fully recovered from the procedure, and breathed spontaneously for 1 week, with no apparent limitations. Increasing respiratory distress then developed, and the animal died.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult psychological functioning of individuals born with craniofacial anomalies.

This study represents an initial investigation into the adult psychological functioning of individuals born with craniofacial disfigurement. A total of 24 men and women born with a craniofacial anomaly completed paper and pencil measures of body image dissatisfaction, self-esteem, quality of life, and experiences of discrimination. An age- and gender-matched control group of 24 non-facially disfigured adults also completed the measures. As expected, craniofacially disfigured adults reported greater dissatisfaction with their facial appearance than did the control group. Craniofacially disfigured adults also reported significantly lower levels of self-esteem and quality of life. Dissatisfaction with facial appearance, self-esteem, and quality of life were related to self-ratings of physical attractiveness. More than one-third of craniofacially disfigured adults (38 percent) reported experiences of discrimination in employment or social settings. Among disfigured adults, psychological functioning was not related to number of surgeries, although the degree of residual facial deformity was related to increased dissatisfaction with facial appearance and greater experiences of discrimination. Results suggest that adults who were born with craniofacial disfigurement, as compared with non-facially disfigured adults, experience greater dissatisfaction with facial appearance and lower self-esteem and quality of life; however, these experiences do not seem to be universal.

Age-dependent closure of bony defects after frontal orbital advancement.

Background: The ability of the immature skull to spontaneously heal large bony defects created after craniofacial procedures was examined over a 25-year period of craniofacial surgery at the Children’s Hospital of Philadelphia. Methods: Only patients who underwent frontal orbital advancement and reconstruction, had at least 1 year of documented follow-up, and had the presence or absence of a bony defect documented on clinical examination were included. The sex, age at operation, diagnosis, history of a prior craniectomy, and presence or absence of a postoperative infection were determined for each patient. A variety of statistics were applied to the data. Results: Eighty-one patients met the inclusion criteria. A statistically significant association between age at operation and closure of bony defect was demonstrated. Children who closed a bony defect after frontal orbital advancement and reconstruction were significantly younger than those children who had a persistent bony defect. Iterative regression analyses demonstrated that a transition point between closure and the inability to close bony defects occurred between 9 and 11 months of age. Closure of bony defects was not statistically associated with sex, prior craniectomy, an FGFR mutation, or a postoperative infection in the regression analysis. Conclusions: Healing of bony defects after frontal orbital advancement and reconstruction is significantly related to age at initial operation, with a mean age for closure of less than 12 months. Between 9 and 11 months of age, a change occurs that results in an increasingly lower probability of bony defect closure; thus, all other considerations being equal, initial frontal orbital advancement and reconstruction would ideally take place before this occurs.

Abdominal Panniculectomies : High Patient Satisfaction Despite Significant Complication Rates

Background:We reviewed our experience with 3 operative techniques for abdominal panniculectomies to determine differences in complication rates and levels of patient satisfaction. Methods:This retrospective study included 92 consecutive patients who underwent abdominal panniculectomies over a 9-year period. Patients underwent one of 3 panniculectomy techniques: fleur-de-lis (n = 25), transverse incisions with minimal undermining (n = 30), or transverse incisions with extensive undermining (n = 37). Postoperatively, patient satisfaction surveys were completed. Results:Median pannus weight was 4.4 kg (range, 1.6–20.5). Sixty-eight patients (73.9%) had a previous gastric bypass. Median body mass index (BMI) was 38 kg/m2 (range, 22–66.9). Median follow-up for complications was 8.1 week (range, 1–235). Forty of 92 patients (43%) suffered wound complications. The reoperation rate was 13%. Postoperative complication rates were higher among hypertensive patients (61% vs. 36%; P = 0.04). There was a trend towards increased complications among those with higher BMI and pannus weights. There was not a significant relationship between operative technique and overall complication rate. Mean length of follow-up for patient questionnaire completion was 2 years, 11 months (range, 1–9 years). Eighty-one percent of those responding to the mailed questionnaire were satisfied with their operative results. There were no statistically significant differences between the technique used and patient satisfaction level. Concomitant hernia repair was performed in 47% of patients without increased wound complications. Conclusions:Patients were satisfied with the results of their panniculectomy, although complications were common. Higher BMI, larger pannus size, and hypertension were correlated with increased complication rates. The minimal undermining, extensive undermining, and the fleur-de-lis panniculectomy techniques result in similar patient satisfaction rates and complication rates.

Engineering new tissue: formation of neo-cartilage.

One approach to tissue-engineering combines isolated cells with polymer scaffolds for the purpose of generating new tissue or tissue equivalents. It has met with much success when applied to the formation of new cartilage (neo-cartilage). In this review, we will examine the development of polyglycolic acid fiber meshes and calcium alginate gels that when combined with chondrocytes generate new cartilage. Animal models designed to mimic clinical problems will also be discussed. Using the chondrocyte-polymer systems as paradigms, we will attempt to extract some principles of tissue engineering.

Incidence of Precancerous Lesions in Breast Reduction Tissue: A Pathologic Review of 562 Consecutive Patients

Background: Reduction mammaplasty is the fifth most common reconstructive surgical procedure in the United States. The incidence of invasive breast cancer in breast reduction specimens is between 0.06 and 0.4 percent. However, the incidence of atypical hyperplasia and other precancerous lesions is not well described. Methods: The authors conducted a single-center retrospective chart review examining the incidence of benign and precancerous lesions in breast reduction specimens over a 5-year period. Results: Of the 562 patients who underwent reduction mammaplasty, 52.7 percent had nonproliferative or proliferative breast lesions. Twenty-five patients (4.4 percent) had a specimen containing atypical ductal or lobular hyperplasia. Six patients (1.1 percent) had ductal carcinoma in situ and four patients (0.7 percent) had lobular carcinoma in situ. No occult invasive breast cancer was identified in the breast reduction specimens, but one patient with ductal carcinoma in situ was found to have invasive breast cancer on completion mastectomy (0.2 percent). Conclusion: This study demonstrates the importance of systematic analysis of breast reduction specimens to help identify and guide the management of patients with increased risk of breast cancer following reduction mammaplasty.