Patches in Congenital Diaphragmatic Hernia: Systematic Review.

OBJECTIVE: This systematic review aims to evaluate current choices in practice and outcomes of biomaterials used in patch repair of congenital diaphragmatic hernia (CDH). BACKGROUND: Multiple biomaterials, both novel and combinations of pre-existing materials are employed in patch repair of large size CDHs. METHODS: A literature search was performed across Embase, Medline, Scopus, and Web of Science. Publications that explicitly reported patch repair, material used, and recurrences following CDH repair were selected. RESULTS: Sixty-three papers were included, presenting data on 4595 patients, of which 1803 (39.2%) were managed using 19 types of patches. Goretex® (GTX) (n=1106) was the most frequently employed patch followed by Dualmesh® (n=267), Surgisis® (n=156), Marlex®/GTX® (n=56), Tutoplast dura® (n=40), Dacron® (n=34), Dacron®/GTX® (n=32), Permacol® (n=24), Teflon® (n=24), Surgisis®/GTX® (n=15), Sauvage® Filamentous Fabric (n=13), Marlex® (n=9), Alloderm® (n=8), Silastic® (n=4), Collagen coated Vicryl® mesh (CCVM) (n=1), Mersilene® (n=1), and MatriStem® (n=1) Biomaterials were further subgrouped as: synthetic nonresorbable (SNOR) (n=1458), natural resorbable (NR) (n=241), combined natural and synthetic nonresorbable (NSNOR) (n=103), and combined natural and synthetic resorbable (NSR) (n=1). The overall recurrence rate for patch repair was 16.6% (n=299). For patch types with n>20, recurrence rate was lowest in GTX/Marlex (3.6%), followed by Teflon (4.2%), Dacron (5.6%), Dualmesh (12.4%), GTX (14.8%), Permacol (16.0%), Tutoplast Dura (17.5%), SIS/GTX (26.7%), SIS (34.6%), and Dacron/GTX (37.5%).When analyzed by biomaterial groups, recurrence was highest in NSR (100%), followed by NR (31.5%), NSNOR (17.5%), and SNOR the least (14.0%). CONCLUSION: In this cohort, over one-third of CDH were closed using patches. To date, 19 patch types/variations have been employed for CDH closure. GTX is the most popular, employed in over 60% of patients; however, excluding smaller cohorts (n<20), GTX/Marlex is associated with the lowest recurrence rate (3.6%). SNOR was the material type least associated with recurrence, while NSR experienced recurrence in every instance.

Surgical perspectives regarding application of biomaterials for the management of large congenital diaphragmatic hernia defects.

This review focuses on the surgical viewpoints on patch repairs in neonates with large congenital diaphragmatic hernia defects. The main focus  is on the various biomaterials that have been employed to date with regard to their source of origins, degradation properties as well as tissue integration characteristics. Further focus  is on the present knowledge on patch integration when biomaterials are placed in the diaphragmatic defect. The review will also look at the present evidence on the biomechanical characteristics of the most commonly used biomaterials and compares these materials to diaphragmatic tissue to offer more  insight on the present practice of patch repairs in large defects. Since tissue engineering and regenerative medicine has offered another dimension to diaphragmatic replacement, a detailed overview of this technology will be undertaken with regard to cell sourcing, scaffolds, in vitro versus in vivo implants as well as quality of tissue produced, to explore the limitations and the feasibility facing the scientific community in its clinical implementation of skeletal muscle-engineered tissue beyond laboratory research for diaphragmatic replacement.

Tissue repair in neonatal and pediatric surgery: analysis on infections in surgically implanted natural biomaterials.

INTRODUCTION: Over the past 4 decades commercially available natural and synthetic biomaterials have been employed for various reconstructive procedures in the pediatric population. The aim of this study was to identify the types of commercially available natural biomaterials and their areas of application in the pediatric age group. Furthermore, to perform an analysis to identify areas of application and types of biomaterials those have increased susceptibility to infections in the pediatric population. EVIDENCE ACQUISITION: The literature was reviewed from 1970-2015 using a Medline search and data concerning application of different natural biomaterials was collected. Specific search was performed regarding to infections associated with these biomaterials. EVIDENCE SYNTHESIS: The rate of major infection after implantation of the biomaterial in the group of 298 reviewed cases was 5%. Patients with acute burn wounds which were treated with biomaterials presented the group with higher infection rates of 5-33%. CONCLUSIONS: The demand for these biomaterials has exponentially increased due to the worldwide rise in interest in tissue engineering research. Even using the appropriate techniques of implantation and professional postoperative care biomaterial associated infections cannot be eliminated. However, the current rate of infections is not a limiting factor for using the biomaterials in pediatric surgery.

Artificial Intelligence (AI) Based Analysis of In Vivo Polymers and Collagen Scaffolds Inducing Vascularization.

BACKGROUND/AIM: Biomaterials are essential in modern medicine, both for patients and research. Their ability to acquire and maintain functional vascularization is currently debated. The aim of this study was to evaluate the vascularization induced by two collagen-based scaffolds (with 2D and 3D structures) and one non-collagen scaffold implanted on the chick embryo chorioallantoic membrane (CAM). MATERIALS AND METHODS: Classical stereomicroscopic image vascular assessment was enhanced with the IKOSA software by using two applications: the CAM assay and the Network Formation Assay, evaluating the vessel branching potential, vascular area, as well as tube length and thickness. RESULTS: Both collagen-based scaffolds induced non-inflammatory angiogenesis, but the non-collagen scaffold induced a massive inflammation followed by inflammatory-related angiogenesis. Vessels branching points/Region of Interest (Px^2) and Vessel branching points/Vessel total area (Px^2), increased exponentially until day 5 of the experiment certifying a sustained and continuous angiogenic process induced by 3D collagen scaffolds. CONCLUSION: Collagen-based scaffolds may be more suitable for neovascularization compared to non-collagen scaffolds. The present study demonstrates the potential of the CAM model in combination with AI-based software for the evaluation of vascularization in biomaterials. This approach could help to reduce and replace animal experimentation in the pre-screening of biomaterials.

Experience with management of anterior abdominal wall defects using bovine pericard.

During 5 years from 1999 until 2003, our experience with 29 (100%) neonates managed for anterior abdominal wall defects is presented. Twenty-one (72%) neonates presented with gastroschisis and 8 (28%) neonates with giant omphaloceles. The male:female ratio was almost equal in gastroschisis (1:1) while a male predominance was observed in omphaloceles (6:1). A primary closure of the defect was possible in 5 (17%) cases and a single patch along with skin closure was achieved in a further 9 (31%) cases. In 15 (52%) neonates the defect was large and two patches were employed to sufficiently cover the defect. All patients (97%), except one (mortality due to extreme prematurity), were managed successfully. Depending upon the size of the defect and the metabolic condition of the neonate, the defect closure was completed after a mean of 85.7 days. Special protocols were created to manage the bovine pericard patches, which behaved differently to lyophilized dura patches previously used at our center. Integration of the patches was successful in 28 (97%) neonates; however, one neonate with gastroschisis presented significant challenges in the management. Bovine pericard patches are optimal biomaterials for the closure of anterior abdominal wall defects in gastroschisis and omphaloceles.

Straddle injuries in female children and adolescents: 10-year accident and management analysis.

OBJECTIVE: To analyze unintentional straddle injuries in girls with regards to epidemiology, etiology and injury management. METHODS: The hospital database was retrospectively reviewed (1999-2009) for female patients managed for genital trauma. Patients were evaluated based on age, causative factors, type of injury, area of genitals affected, management and outcomes. RESULTS: Straddle injuries were documented in 91 girls with age ranging from 1 to 15 y (mean = 6.3 y; median = 6.1 y). The causes of injuries were falls at home (n = 31) or outdoors (n = 27), and sport activities (swimming pool n = 11, skating n = 11, bicycle n = 9 and scooter n = 2). Most of the injuries were lacerations. Injuries involved major labia (n = 56), minor labia (n = 45) and introitus vaginae (n = 15). Twelve children received outpatient treatment. Inspection under anesthesia was performed in 79 patients, with 76 requiring sutures. While hematuria was observed in 18 patients, cystoscopy did not reveal lesions in the urethra or bladder. Associated injuries were femur fracture (n = 1), lower extremity lacerations (n = 4) and anal lesions (n = 2). Follow-up investigations were uneventful; however one patient developed a secondary abscess and another secondary hyperplasia of the labia minor. CONCLUSIONS: Falls and sports are major causes of straddle injuries with a peak at the age of six years. Lacerations are the most common injuries and often require surgical management. Urinary tract injuries and other associated injuries are relatively uncommon in girls with straddle injuries.

Seamless vascularized large-diameter tubular collagen scaffolds reinforced with polymer knittings for esophageal regenerative medicine.

A clinical demand exists for alternatives to repair the esophagus in case of congenital defects, cancer, or trauma. A seamless biocompatible off-the-shelf large-diameter tubular scaffold, which is accessible for vascularization, could set the stage for regenerative medicine of the esophagus. The use of seamless scaffolds eliminates the error-prone tubularization step, which is necessary when emanating from flat scaffolds. In this study, we developed and characterized three different types of seamless tubular scaffolds, and evaluated in vivo tissue compatibility, including vascularization by omental wrapping. Scaffolds (luminal Ø âˆ¼ 1.5 cm) were constructed using freezing, lyophilizing, and cross-linking techniques and included (1) single-layered porous collagen scaffold, (2) dual-layered (porous+dense) collagen scaffold, and (3) hybrid scaffold (collagen+incorporated polycaprolacton knitting). The latter had an ultimate tensile strength comparable to a porcine esophagus. To induce rapid vascularization, scaffolds were implanted in the omentum of sheep using a wrapping technique. After 6 weeks of biocompatibility, vascularization, calcification, and hypoxia were evaluated using immunohistochemistry. Scaffolds were biocompatible, and cellular influx and ingrowth of blood vessels were observed throughout the whole scaffold. No calcification was observed, and slight hypoxic conditions were detected only in the direct vicinity of the polymer knitting. It is concluded that seamless large-diameter tubular collagen-based scaffolds can be constructed and vascularized in vivo. Such scaffolds provide novel tools for esophageal reconstruction.

Closure of bronchopleural fistula with porcine dermal collagen and fibrin glue in an infant.

The management of an 11-month-old infant who developed a bronchopleural fistula (BPF) 3 weeks after video-assisted thoracic surgery for congenital cystic adenomatoid malformation of the right lower pulmonary lobe is presented. Being refractory to treatment with chest tubes, the BPF was managed using a bronchoscopic approach using porcine dermal collagen (PDC) combined with a fibrin glue plug. The single session was sufficient to manage the BPF and the postoperative course was uneventful. This case highlights the novelty in the successful management of BPF in infants after pulmonary surgery using PDC and fibrin glue using the minimal access bronchoscopic approach.

Culture of ovine esophageal epithelial cells and in vitro esophagus tissue engineering.

BACKGROUND: Esophagus replacement presents major surgical challenges both in the pediatric and in adult patients since the various surgical techniques presently employed are associated with complications and high morbidity. AIM: The aim of this study was to establish protocols for isolation and culture of ovine esophageal epithelial cells (OEEC) and to investigate their viability on collagen scaffolds for in vitro tissue engineering. METHODS: OEEC were sourced from adult Austrian mountain sheep. Briefly, the esophagus was dissected, treated with dispase to separate the epithelial layer, and further subjected to a modified explants technique to isolate OEEC. The OEEC were cultured in vitro and seeded on to unidirectional two-dimensional and three-dimensional collagen scaffolds. RESULTS: Successful protocol was established for OEEC isolation and culture. OEEC exhibited organization and differentiation after 7 days in culture, which was complete after 18 days with the formation of a single layer sheet of differentiated cells exhibiting morphology of mature esophageal epithelium. OEEC seeded on two-dimensional collagen scaffolds demonstrated viability up to 6 weeks of in vitro culture with single layer epithelium formation after 3 weeks confirmed using pan-Cytokeratin markers. OEEC on three-dimensional scaffolds were viable for 6 weeks but did not form an epithelium sheet. CONCLUSION: Protocols for OEEC isolation were developed and established from adult ovine esophageal tissue. The generation of sheets of esophageal epithelium in culture and the viability of OEEC on collagen scaffolds for 6 weeks in vitro was observed. The prerequisite for esophagus tissue engineering, which is the ability to form epithelium when seeded on collagen scaffolds, was demonstrated.

Comparison of suturing techniques in the formation of collagen scaffold tubes for composite tubular organ tissue engineering.

In order to construct tubes for tissue engineering of composite tubular organs in the gastrointestinal tract, suturing techniques were investigated with regards to (a) type of suture material, (b) state of scaffold, (c) technical variations and (d) changes in scaffold morphology. Collagen scaffolds of 13 mm diameter and 3 mm thickness, in both dry and wet states, were sutured using braided and monofilament sutures. Four suture techniques were employed (a) continuous loop, (b) interrupted loops, (c) interrupted edge sutures and (d) continuous running edge suture. Scanning electron microscopic imaging was performed on the 4 tubes sutured. Monofilament sutures were used for tube formation as braided sutures were unsuitable. Dry scaffolds demonstrated tears during knot tying and fractures when bent around a stent. The interrupted and continuous running edge suture were the most suitable suturing techniques in wet scaffolds; further confirmed by scanning electron microscopy imaging. Our approach to tissue engineer segments of the gastrointestinal tract involves cell-seeding on scaffolds to permit attachment in vitro and later wrapping of scaffold layers of heterogeneous cells to create composite tissue. Scaffolds in wet state can be better sutured with monofilament materials using either the interrupted or running continuous edge suture technique.

Micro-computed tomography for implantation site imaging during in situ oesophagus tissue engineering in a live small animal model.

For tissue engineering of gastrointestinal organs, in situ implantation of constructs in the omentum is performed to utilize the body as a bioreactor for tissue generation. In this approach, constructs are fabricated into tubes, using stents, and implanted in the omentum to induce vascularization. In order to evaluate the constructs and its environment during the period of in situ tissue engineering in the rat model, micro-computed tomography imaging was performed. Imaging using micro-computed tomography was useful in localization of the position of the construct, evaluation of implant site tissue, degree of peripheral inflammation to neighbouring tissues and migration of the implanted construct. Images also enable the estimation of the dimensions of the construct and imaging of cyst formations or fluid accumulations on the luminal side of the tubular construct or ascites formation. Since micro-computed tomography is a non-invasive method, it can be repeated for evaluation of implanted constructs if in situ tissue engineering is performed over longer periods.

Esophagus tissue engineering: hybrid approach with esophageal epithelium and unidirectional smooth muscle tissue component generation in vitro.

PURPOSE: The aim of this study was to engineer the two main components of the esophagus in vitro: (a) esophageal epithelium and (b) smooth muscle tissue. Furthermore, (a) survivability of esophageal epithelial cells (EEC) on basement membrane matrix (BMM)-coated scaffolds and (b) oriented smooth muscle tissue formation on unidirectional BMM-coated collagen scaffolds was investigated. METHODS: Both EEC and smooth muscle cells (SMC) were sourced from Sprague-Dawley rats. The EEC were maintained in vitro and seeded onto BMM-coated 2-D collagen scaffolds. Similarly, smooth muscle cells were obtained using an explants technique and seeded on unidirectional 3-D BMM-coated collagen scaffolds. Cell-polymer constructs for EEC and SMC were maintained in vitro for 8 weeks. RESULTS: Protocols to obtain higher yield of EEC were established. EEC formed a layer of differentiated epithelium after 14 days. EEC survivability on polymers was observed up to 8 weeks. Unidirectional smooth muscle tissue strands were successfully engineered. CONCLUSION: Esophageal epithelium generation, survivability of EEC on BMM-coated scaffolds, and engineering of unidirectional smooth muscle strands were successful in vitro. The hybrid approach of assembling individual tissue components in vitro using BMM-coated scaffolds and later amalgamating them to form composite tissue holds promises in the tissue engineering of complex organ systems.