Evaluating the impact of a street outreach intervention on participant involvement in gun violence.

The past several years have witnessed increased calls for community violence interventions (CVIs) that address firearm violence while centering local expertise and avoiding the criminal legal system. Currently, little evidence exists on CVI effectiveness at the individual level. This study presents an evaluation of the impact of a street outreach-based CVI [Chicago CRED (Create Real Economic Destiny)] on participant involvement in violence. We used a quasiexperimental design with a treatment sample of 324 men recruited by outreach staff from 2016 to 2021 and a balanced comparison sample of 2,500 men from a network of individuals arrested in CRED's service areas. We conducted a Bayesian survival analysis to evaluate CRED's effect on individual violence-related outcomes on three levels of treatment: All enrolled participants, a subsample that made it through the initial phase, and those who completed programming. The intervention had a strong favorable effect on the probability of arrest for a violent crime for those completing the program: After 24 mo, CRED alumni experienced an 11.3 percentage point increase in survival rates of arrest for a violent crime relative to their comparisons (or, stated differently, a 73.4% reduction in violent crime arrests). The other two treatment levels experienced nontrivial declines in arrests but did not reach statistical significance. No statistically significant reduction in victimization risk was detected for any of the treatment levels. Results demonstrate that completion of violence intervention programming reduces the likelihood of criminal legal involvement for participants, despite the numerous systemic and environmental factors that impede personal success.

Tissue-engineered small intestine and stomach form from autologous tissue in a preclinical large animal model.

BACKGROUND: Tissue-engineered small intestine, stomach, large intestine, esophagus, and gastroesophageal (GE) junction have been successfully formed from syngeneic cells, and employed as a rescue therapy in a small animal model. The purpose of this study is to determine if engineered intestine and stomach could be generated in an autologous, preclinical large animal model, and to identify if the tissue-engineered intestine retained features of an intact stem cell niche. METHODS: A short segment of jejunum or stomach was resected from 6-wk-old Yorkshire swine. Organoid units, multicellular clusters with predominantly epithelial content, were generated and loaded onto biodegradable scaffold tubes. The constructs were then implanted intraperitoneally in the autologous host. Seven wk later, all implants were harvested and analyzed using histology and immunohistochemistry techniques. RESULTS: Autologous engineered small intestine and stomach formed. Tissue-engineered intestinal architecture replicated that of native intestine. Histology revealed tissue-engineered small intestinal mucosa composed of a columnar epithelium with all differentiated intestinal cell types adjacent to an innervated muscularis mucosae. Intestinal subepithelial myofibroblasts, specialized cells that participate in the stem cell niche formation, were identified. Moreover, cells positive for the putative intestinal stem cell marker, doublecortin and CaM kinase-like-1 (DCAMKL-1) expression were identified at the base of the crypts. Finally, tissue-engineered stomach also formed with antral-type mucosa (mucus cells and surface foveolar cells) and a muscularis. CONCLUSION: We successfully generated tissue-engineered intestine with correct architecture, including features of an intact stem cell niche, in the pig model. To our knowledge, this is the first demonstration in which tissue-engineered intestine was successfully generated in an autologous manner in an animal model, which may better emulate a human host and the intended therapeutic pathway for humans.

Sleeping Beauty-mediated suicide gene therapy of hepatocellular carcinoma.

The aim of this study was to use gene therapy via the Sleeping Beauty (SB) system to increase telomerase promoter activity to target hepatocellular carcinoma (HCC). In previous studies, we identified selective and increased expression of luciferase and suicide genes controlled by the hTERT (human telomerase reverse transcriptase) promoter and the SV40 enhancer in telomerase-positive cancer cell lines. Because telomerase is activated in about 80% of HCCs, it is likely that increasing the activity of the telomerase promoter with a suicide gene will effectively eradicate HCCs. We found that the telomerase promoter mediated SB system can efficiently insert transgene into HCC genomes. Also, telomerase promoter activity was increased using a SB vector expressing suicide gene HSV-TK (herpes simplex virus thymidine kinase) controlled by the hTERT promoter and a SV40 enhancer for the induction of telomerase-positive cancer-specific cell death. HCC cell lines transfected with pT.hTp.HSV-tk.Con with active helper plasmid and ganciclovir (GCV) significantly inhibited cancer cell growth. These results indicate that Sleeping Beauty transposon mediated suicide gene expression can be used in HCC-targeted cancer gene therapy.

Expression of specific hepatocyte and cholangiocyte transcription factors in human liver disease and embryonic development.

Transcription factors are major determinants of cell-specific gene expression in all cell types. Studies in rodent liver have shown that alterations in transcription factor expression determine lineage specification during fetal liver development and signify transdifferentiation of cells of the biliary compartment into 'oval' cells and eventually hepatocytes in adult liver. We examined the cellular localization of hepatocyte- or BEC-associated transcription factors in human fetal and adult liver and in diseases in which transdifferentiation between hepatocytes and biliary cells may play a role. In the normal adult human liver, hepatocyte nuclear factor (HNF)4 alpha and HNF6 appeared exclusively in hepatocytes; HNF1beta, HNF3alpha, and HNF3beta were observed only in BEC. During fetal development both BEC and hepatocytes expressed HNF3alpha, HNF3beta, and HNF6. HNF1alpha was expressed only in fetal hepatocytes. We further examined expression of transcription factors in massive hepatic necrosis and in specific types of chronic liver disease. Hepatocyte-associated transcription factors HNF4 alpha and HNF6 also appeared in BEC in massive hepatic necrosis and chronic hepatitis C virus infection. Similarly, HNF3beta that is expressed only in BEC in normal adult liver was also observed in hepatocytes in primary biliary cirrhosis and chronic biliary obstruction. These data mimic previous findings in rodents in which hepatocyte-associated transcription factors appear in biliary cells prior to emergence of oval cells, which function as progenitor cells for hepatocytes when the regenerative capacity of the latter is compromised.

Surgical management of hepatocellular adenoma: take it or leave it?

BACKGROUND: Hepatocellular adenoma (HA) is a rare benign tumor of the liver. Surgical resection is generally indicated to reduce risks of hemorrhage and malignant transformation. We sought to evaluate clinical presentation, surgical management, and outcomes of patients with HA at our institution. METHODS: We performed a retrospective review of 41 patients who underwent surgical resection for HA between 1988 and 2007. RESULTS: Thirty-eight patients were women, and the median age at presentation was 36 years (range, 19-65 years). The most common clinical presentation was abdominal pain (70%) followed by incidental radiological finding (17%). Twenty-two patients had a history of oral contraceptive use. Median number of HA was one (range, 1-3). There were 32 open cases (3 trisectionectomy, 15 hemihepatectomy, 7 sectionectomy, 4 segmentectomy, and 3 wedge resection), and 9 laparoscopic cases (1 hemihepatectomy, 5 sectionectomy, 1 segmentectomy, and 2 wedge resection). The median estimated blood loss was 225 mL (range, 0-3400 mL). The median length of stay was 6 days (range, 1-15 days). Surgical morbidities included pleural effusion requiring percutaneous drainage (n = 2), pneumonia (n = 1), and wound infection (n = 1). There was no perioperative mortality. Twelve patients had hemorrhage from HA. Hepatocellular carcinoma was observed in two patients with HA. Median follow-up was 23 months (range, 1-194 months), at which time all patients were alive. CONCLUSION: In view of 29% hemorrhagic and 5% malignant complication rates, we recommend surgical resection over observation if patient comorbidities and anatomic location of HA are favorable. A laparoscopic approach can be safely used in selected cases.

Tissue-engineered spleen protects against overwhelming pneumococcal sepsis in a rodent model.

BACKGROUND/PURPOSE: Solid organs production is an ultimate goal of tissue engineering. After refining a technique for intestinal engineering, we applied it to a solid organ, the spleen. Overwhelming postsplenectomy sepsis results in death in nearly half of all cases. This risk is pronounced in children. Necrosis of autotransplanted spleen slices occurs prior to regeneration. We postulate that tissue engineering techniques might be superior. METHODS: Four groups of Lewis rats were compared: sham laparotomy, tissue-engineered spleen (TES), traditional spleen slices, and splenectomy. TES was generated from splenic units, multicellular components of juvenile spleen implanted on a biodegradable polymer scaffold, and spleen slices were derived from age-matched juveniles. Pneumococcal sepsis was induced at wk 16, and survival curves were constructed. RESULTS: Tissue-engineered spleen protected against pneumococcal septicemia with a survival proportion of 85.7% compared with 41.17% of splenectomized animals. Spleen slice was also protective with 71.43% survival. Compared with splenectomy, control and TES groups were statistically significant (P = 0.0002, P = 0.0087; hazard ratio of splenectomy = 5.493) and the Slice group was nearly statistically significant (P = 0.0642, hazard ratio of splenectomy = 2.673). CONCLUSIONS: TES is a novel application of tissue engineering to splenic regeneration and creates a functional spleen. This approach could be advantageous in severe pediatric trauma.

The generation of functionally differentiated, three-dimensional hepatic tissue from two-dimensional sheets of progenitor small hepatocytes and nonparenchymal cells.

BACKGROUND: The authors' laboratory has investigated tissue engineering of the liver as a novel approach for treating end-stage liver disease. Fabrication of thick, viable, three-dimensional liver tissue is limited by the lack of vascularity in the tissue-engineered constructs. To overcome this limitation, the authors fabricated three-dimensional, vascularized liver tissue in vivo from two-dimensional cell sheets created from small hepatocytes (SHC) and nonparenchymal cells (NPC) implanted into rat omentum. METHODS: SHC and NPC were cultured on a silicon wafer and lifted as monolayer cell sheets. After maximal hepatotrophic stimulation was induced in the host by injecting retrorsine, creating a portacaval shunt, and performing a partial hepatectomy, these sheets were placed onto the omentum and then rolled into a three-dimensional cylinder. RESULTS: New tissue consisting of both hepatocytes and bile duct-like structures formed by 2 weeks, and the mass of hepatocytes increased in size up to 2 months. The hepatocytes in these constructs were immunohistochemically positive for albumin and transferrin, and bile duct-like structures were positive for gamma-glutamyl transpeptidase, which suggests that they possess liver-specific function. Electron microscopy also revealed structures resembling bile canaliculi. CONCLUSIONS: Functional, morphologically complex new tissue was generated from morphologically simple monolayer cell sheets of SHC and NPC. These results represent an essential step toward the design of tissue-engineered complex vascularized thick tissue.

Evaluation of hepatic histology by near-infrared confocal microscopy: a pilot study.

Liver biopsy is a necessary procedure in establishing the tissue diagnosis of many liver conditions and often guides therapeutic strategies. Current histopathologic techniques are either time-consuming or tissue-destroying; hence the potential need for a fast and nondestructive imaging technique of unfixed human liver. This pilot study evaluates the use of near-infrared reflectance confocal microscopy (CM) in the study of human liver histopathology. Without cutting or staining the tissue, CM provides images of bulk parenchyma showing cellular and subcellular detail and depicting morphologic features of hepatic parenchyma in both diseased and nondiseased states. This article presents a series of 12 human liver biopsy samples, providing an overview on the potential of this technique in assessing common findings from light microscopy.

Tissue-engineered esophagus: experimental substitution by onlay patch or interposition.

OBJECTIVES: We proposed to fabricate a tissue-engineered esophagus and to use it for replacement of the abdominal esophagus. METHODS: Esophagus organoid units, mesenchymal cores surrounded by epithelial cells, were isolated from neonatal or adult rats and paratopically transplanted on biodegradable polymer tubes, which were implanted in syngeneic hosts. Four weeks later, the tissue-engineered esophagus was either harvested or anastomosed as an onlay patch or total interposition graft. Green Fluorescent Protein labeling by means of viral infection of the organoid units was performed before implantation. Histology and immunohistochemical detection of the antigen alpha-actin smooth muscle were performed. RESULTS: Tissue-engineered esophagus grows in sufficient quantity for interposition grafting. Histology reveals a complete esophageal wall, including mucosa, submucosa, and muscularis propria, which was confirmed by means of immunohistochemical staining for alpha-actin smooth muscle. Tissue-engineered esophagus architecture was maintained after interposition or use as a patch, and animals gained weight on a normal diet. Green Fluorescent Protein-labeled tissue-engineered esophagus preserved its fluorescent label, proving the donor origin of the tissue-engineered esophagus. CONCLUSIONS: Tissue-engineered esophagus resembles the native esophagus and maintains normal histology in anastomosis, with implications for therapy of long-segment esophageal tissue loss caused by congenital absence, surgical excision, or trauma.

Dynamic rotational seeding and cell culture system for vascular tube formation.

Optimization of cell seeding and culturing is an important step for the successful tissue engineering of vascular conduits. We evaluated the effectiveness of using a hybridization oven for rotational seeding and culturing of ovine vascular myofibroblasts onto biodegradable polymer scaffolds suitable for replacement of small- and large-diameter blood vessels. Large tubes (12 mm internal diameter and 60 mm length, n = 4) and small tubes (5 mm internal diameter and 20 mm length, n = 4) were made from a combination of polyglycolic acid/poly-4-hydroxybutyrate and coated with collagen solution. Tubes were then placed in culture vessels containing a vascular myofibroblast suspension (10(6) cells/cm(2)) and rotated at 5 rpm in a hybridization oven at 37 degrees C. Light and scanning electron microscopy analyses were performed after 5, 7, and 10 days. Myofibroblasts had formed confluent layers over the outer and inner surfaces of both large and small tubular scaffolds by day 5. Cells had aligned in the direction of flow by day 7. Multiple spindle-shaped cells were observed infiltrating the polymer mesh. Cell density increased between day 5 and day 10. All conduits maintained their tubular shape throughout the experiment. We conclude that dynamic rotational seeding and culturing in a hybridization oven is an easy, effective, and reliable method to deliver and culture vascular myofibroblasts onto tubular polymer scaffolds.

An overview of the pathology and approaches to tissue engineering.

In tissue engineering, there is an attempt to culture living tissues for surgical transplantation. In vitro and in vivo approaches have produced vascular and cardiovascular components, cartilage, bone, intestine, and liver. Attempts to microdesign cell-culture support scaffolds have used a new generation of biocompatible and bioabsorbable polymers. Suspensions of donor cells are seeded onto protein-coated polymer scaffolds and grown to confluence in dynamic bioreactors. In vitro techniques produce monolayers of tissues. Denser masses are achieved by implanting monolayers onto a host, or by culturing cell/polymer constructs in vivo. Existing techniques have produced functioning heart valves from sheep endothelial cells and myofibroblasts. Cultured ovine arterial cells have replaced 2-cm segments of pulmonary artery in lambs. Chondrocyte cultures have produced a human-ear-shaped construct, temporo-mandibular joint discs, meniscal replacement devices, and human-phalange-shaped constructs, complete with a joint. The culture of composite tissue types has recently been reported. Intestinal organoid units containing a mesenchymal core with surrounding polarized epithelia have been used in lieu of an ileal pouch in Lewis rats, and the long-term culture of rat hepatocytes has revealed cellular differentiation and neomorphology resembling elements of a biliary drainage system. To sustain the in vitro culture of dense tissues prior to implantation, micro-electro-mechanical systems (MEMS) fabrication technologies have been adapted to create wafers of polymer containing sealed, branching, vascular-type spaces. After seeding with rat lung endothelial cells, followed by 5 days of bioreactor culture, the result is an endothelial network with controlled blood flow rates, pressure, and hematocrit. When these customized vascular systems can be used to support in vitro culture, a new generation of dense, composite, morphologically complex tissues will be available for clinical development.

Tissue-engineered colon exhibits function in vivo.

BACKGROUND: Postcolectomy morbidities include important changes in enterohepatic circulation, stool microbiology, and absorption. The surgical substitution of an ileal pouch for the absent colon also has a number of serious complications. We report in vivo colon replacement by tissue-engineered colon (TEC) in lieu of an ileal pouch. METHODS: End-ileostomies were created in 22 male Lewis rats. In 11 animals, side-to-side ileum-TEC anastomosis was performed 1 cm from the stoma. This group was compared with end-ileostomy alone. Serial weights were measured, and animals were harvested sequentially for assessment of histologic signs of pouchitis. Transit times, stool dry and wet weights, and serum and stool colon function markers were collected. RESULTS: Animals survived 41 days. Weight loss was more than 1.5 times greater in the end-ileostomy alone group compared with the ileum-TEC group. Transit times were significantly longer in the ileum-TEC group than the end-ileostomy alone group, with lower stool moisture content and higher total serum bile acids. Animals without TEC had statistically significant hyponatremia, elevated serum urea nitrogen, and lower stool short chain fatty acids (13.5 micromol/kg vs 84.2) with an abnormal distribution. CONCLUSIONS: TEC successfully recapitulates some major physiologic functions of native large intestine in vivo.

Posttransplant adenoviral enteropathy in patients with small bowel transplantation.

Transplant patients on immunosuppression represent a risk group for opportunistic infections, including adenoviral infections. The clinical and histopathologic findings of posttransplant adenoviral enteropathy in 3 adult intestinal transplant patients are described. The histopathologic pitfalls for the differential diagnosis between intestinal adenoviral enteropathy and acute rejection are discussed. Adenoviral enteropathy is an opportunistic infection that may follow aggressive treatment for small bowel allograft rejection, but which may require no specific treatment. It is associated with mild mixed inflammation in the lamina propria and slight increase of crypt apoptosis, resembling low-grade acute rejection. The identification of characteristic viral inclusions in the surface or crypt epithelium points to the diagnosis of adenoviral enteropathy, in spite of the increased crypt apoptosis.

Protection from acute cellular injury using Sleeping Beauty mediated telomerase gene transfer.

We developed a Sleeping Beauty (SB) transposon mediated hTERT gene delivery system for in vitro use. We have constructed telomerase or luciferase gene expressing SB-transposons with a SV40 enhancer (pT3.hTERT.Con and pT3.Con, respectively) or without an enhancer (pT3.Pro). Using the SB transposon system in vitro hTERT gene overexpression has protective effects from acute cellular injury by tert-butyl hydroperoxide (t-BH), carbon tetrachloride (CCl(4)), and d-galactosamine (d-GalN) in normal human cells IMR-90. pT3.hTERT.Con vector and helper plasmid co-transfection resulted in a approximately 3-fold increase in telomerase activity which was maintained for 14 days. Trypan blue and Cell Death Detection Assays showed the protective effects of the telomerase gene against toxic agents. Fourteen days after co-transfection with pT3.hTERT.Con vector and helper plasmid, IMR-90 cells were incubated with 1.2mM t-BH for 50 min, 5mM CCl(4) for 1.5h or 30 mM d-GalN for 24h. Cell viability of SB-mediated telomerase overexpressing cells significantly increased by 48% (t-BH), 43% (CCl(4)), and 25% (d-GalN) in comparison to mock treated cells. Cell Death Detection ELISA showed a decrease in the rate of apoptosis by 47%. In summary, SB transposon mediated telomerase gene transfer may have a protective effect against t-BH, CCl(4), or d-GalN induced acute cellular injury, and this results suggested SB-mediated telomerase therapy for tissue engineering.

Liver biopsy interpretation for causes of late liver allograft dysfunction.

Evaluation of needle biopsies and extensive clinicopathological correlation play an important role in the determination of liver allograft dysfunction occurring more than 1 year after transplantation. Interpretation of these biopsies can be quite difficult because of the high incidence of recurrent diseases that show histopathological, clinical, and serological features that overlap with each other and with rejection. Also, more than one insult can contribute to allograft injury. In an attempt to enable centers to compare and pool results, improve therapy, and better understand pathophysiological disease mechanisms, the Banff Working Group on Liver Allograft Pathology herein proposes a set of consensus criteria for the most common and problematic causes of late liver allograft dysfunction, including late-onset acute and chronic rejection, recurrent and new-onset viral and autoimmune hepatitis, biliary strictures, and recurrent primary biliary cirrhosis and primary sclerosing cholangitis. A discussion of differential diagnosis is also presented.

Fetal tissue engineering: in vitro analysis of muscle constructs.

BACKGROUND/PURPOSE: This study was aimed at examining the impact of different tissue engineering techniques on fetal muscle construct architecture. METHODS: Myoblasts from ovine specimens of fetal skeletal muscle were expanded in culture and their growth rates determined. Cells were seeded at different densities onto 3 scaffold types, namely polyglycolic acid (PGA) treated with poly-l-lactic acid (PLLA), a composite of PGA with poly-4-hydroxybutyrate (P4HB), and a collagen hydrogel. Constructs were maintained in a bioreactor and submitted to histologic, scanning electron microscopy, and DNA analyses at different time-points. Statistical analysis was by the likelihood ratio and paired Student's t tests (P <.05). RESULTS: Fetal myoblasts proliferated at faster rates than expected from neonatal cells. Cell attachment was enhanced in the PGA/PLLA matrix and collagen hydrogel when compared with the PGA/P4HB composite. Necrosis was observed at the center of all constructs, directly proportional to cell seeding density and time in the bioreactor. CONCLUSIONS: Fetal myoblasts can be expanded rapidly in culture and attach well to PGA/PLLA, as well as collagen hydrogel but less optimally to PGA/P4HB. Excessive cell seeding density and bioreactor time may worsen final construct architecture. These findings should be considered during in vivo trials of muscle replacement by engineered fetal constructs.

Fetal tissue engineering: in utero tracheal augmentation in an ovine model.

BACKGROUND/PURPOSE: This study was aimed at comparing fetal tissue engineering with autologous free grafting in an ovine model of in utero tracheal repair. METHODS: Chondrocytes were isolated from both elastic and hyaline cartilage specimens harvested from fetal lambs and expanded in vitro. Cells were seeded dynamically onto biodegradable scaffolds, which then were maintained in a rotating bioreactor for 6 to 8 weeks. Constructs subsequently were implanted into fetal tracheas (n = 15), in a heterologous fashion (group I). In group II, fetuses (n = 5) received autologous free grafts of elastic cartilage harvested from the ear as tracheal implants. In vivo specimens were harvested for histologic analysis at different time-points postimplantation. RESULTS: In the 12 of 15 surviving fetuses of group I, all constructs were found to resemble normal hyaline cartilage, engraft well despite their heterologous origin, and display time-dependent epithelialization derived from the native trachea. All autologous free grafts were engrafted and epithelialized at birth, retaining histologic characteristics of elastic cartilage, but were more deformed than engineered constructs. Of the lambs allowed to reach term, 5 of 5 in the engineered group and 4 of 5 in the free graft group could breathe spontaneously. CONCLUSIONS: (1) Tissue-engineered cartilage, as well as autologous free grafts, can be implanted successfully into the fetal trachea, resulting in engraftment and function. (2) Engineered cartilage provides enhanced structural support after implantation into the fetal trachea when compared with free grafts. Prenatal tracheoplasty may prove useful for the treatment of severe congenital tracheal malformations.

Tissue-engineered small intestine improves recovery after massive small bowel resection.

OBJECTIVE: Rescue with tissue-engineered small intestine (TESI) after massive small bowel resection (MSBR). SUMMARY BACKGROUND DATA: Short bowel syndrome is a morbid product of massive small bowel resection. We report the first replacement of a vital organ by tissue engineering with TESI after MSBR. METHODS: Ten male Lewis rats underwent TESI implantation with green fluorescent protein (GFP)-marked cells (TESI+, n = 5) or sham laparotomy (TESI-, n = 5) followed by MSBR. Side-to-side anastomosis of TESI to proximal small intestine was performed or omitted. TESIO animals underwent implantation of engineered intestine with no further surgery. Weights were measured QOD until day 40. Transit times were measured. DNA assay was performed with computer morphometry. Northern blots of RNA were probed for intestinal alkaline phosphatase (IAP) and villin. Hematoxylin and eosin, S100, and smooth muscle actin immunohistochemistry were performed. Blood was collected at sacrifice. RESULTS: All 10 rats initially lost then regained weight. The initial rate of weight loss was higher in TESI+ versus TESI-, but the nadir was reached a week earlier with more rapid weight gain subsequently to 98% preoperative weight on day 40 in animals with engineered intestine versus 76% (P < 0.03). Serum B12 was higher at 439 pg/mL versus 195.4 pg/mL. IAP mRNA appeared greater in TESI+ than TESIO, with constant villin levels. Histology revealed appropriate architecture including nerve. GFP labeling persisted. CONCLUSIONS: Anastomosis of TESI significantly improved postoperative weight and B12 absorption after MSBR. IAP, a marker of differentiation in intestinal epithelium, is present in TESI, and GFP labeling was accomplished.

Fetal tissue engineering: chest wall reconstruction.

BACKGROUND/PURPOSE: This study was aimed at applying fetal tissue engineering to chest wall reconstruction. METHODS: Fetal lambs underwent harvest of elastic and hyaline cartilage specimens. Once expanded in vitro, fetal chondrocytes were seeded onto synthetic scaffolds, which then were placed in a bioreactor. After birth, fetal cartilage constructs (n = 10) were implanted in autologous fashion into the ribs of all lambs (n = 6) along with identical, but acellular scaffolds, as controls (n = 6). Engineered and acellular specimens were harvested for analysis at 4 to 12 weeks postimplantation. Standard histology and matrix-specific staining were performed both before implantation and after harvest on all constructs. RESULTS: Regardless of the source of chondrocytes, all fetal constructs resembled hyaline cartilage, both grossly and histologically, in vitro. In vivo, engineered implants retained hyaline characteristics for up to 10 weeks after implantation but remodeled into fibrocartilage by 12 weeks postoperatively. Mononuclear inflammatory infiltrates surrounding residual PGA/PLLA polymer fibers were noted in all specimens but most prominently in the acellular controls. CONCLUSIONS: Engineered fetal cartilage can provide structural replacement for at least up to 10 weeks after autologous, postnatal implantation in the chest wall. Fetal tissue engineering may prove useful for the treatment of severe congenital chest wall defects at birth.