Diaphragm Repair with a Novel Cross-Linked Collagen Biomaterial in a Growing Rabbit Model

Abstract

BackgroundNeonates with congenital diaphragmatic hernia and large defects often require patch closure. Acellular collagen matrices (ACM) have been suggested as an alternative to synthetic durable patches as they are remodeled by the host or could also be used for tissue engineering purposes.Materials and Methods2.0x1.0 cm diaphragmatic defects were created in 6-weeks old New-Zealand white rabbits. We compared reconstruction with a purpose-designed cross-linked ACM (Matricel) to 4-layer non-cross-linked small intestinal submucosa (SIS) and a 1-layer synthetic Dual Mesh (Gore-Tex). Unoperated animals or animals undergoing primary closure (4/0 polyglecaprone) served as age-matched controls. 60 (n = 25) resp. 90 (n = 17) days later, animals underwent chest x-ray and obduction for gross examination of explants, scoring of adhesion and inflammatory response. Also, uniaxial tensiometry was done, comparing explants to contralateral native diaphragmatic tissue.ResultsOverall weight nearly doubled from 1,554±242 g at surgery to 2,837±265 g at obduction (+84%). X-rays did show rare elevation of the left diaphragm (SIS = 1, Gore-Tex = 1, unoperated control = 1), but no herniation of abdominal organs. 56% of SIS and 10% of Matricel patches degraded with visceral bulging in four (SIS = 3, Matricel = 1). Adhesion scores were limited: 0.5 (Matricel) to 1 (SIS, Gore-Tex) to the left lung (p = 0.008) and 2.5 (Gore-Tex), 3 (SIS) and 4 (Matricel) to the liver (p<0.0001). Tensiometry revealed a reduced bursting strength but normal compliance for SIS. Compliance was reduced in Matricel and Gore-Tex (p<0.01). Inflammatory response was characterized by a more polymorphonuclear cell (SIS) resp. macrophage (Matricel) type of infiltrate (p<0.05). Fibrosis was similar for all groups, except there was less mature collagen deposited to Gore-Tex implants (p<0.05).ConclusionsMatricel induced a macrophage-dominated inflammatory response, more adhesions, had appropriate strength but a lesser compliance compared to native tissue. The herein investigated ACM is not a viable option for CDH repair.

Primary Combined Latissimus Dorsi and Serratus Anterior Flap Repair of Right-Sided Congenital Diaphragmatic Agenesis in a Neonate

“…16 Primary reconstruction with living bio-tissue avoids the complications of synthetic mesh repairs. The serratus anterior muscle originates from the lateral scapula and fans anteriorly into the first nine ribs.…”

Providing direction improves function: Comparison of a radial pore-orientated acellular collagen scaffold to clinical alternatives in a surgically induced rabbit diaphragmatic tissue defect model

“…In children born with CDH requiring defect closure, a Gore‐Tex patch is the most commonly used patch (Gasior & St Peter, ). This synthetic durable material has a compliance that is different from diaphragmatic tissue, which may hamper fluid diaphragmatic movements (Mayer et al, ; Touloukian, ). Furthermore, it is not remodelled and does not grow with the neonate, thus potentially leading to reherniation, chest wall, and spinal deformities (Gasior & St Peter, ; Takayasu et al, ).…”

A growing animal model for neonatal repair of large diaphragmatic defects to evaluate patch function and outcome

“…In brief, a semi-rigid guide wire (TSF-35-145, 0.35”, 145cm; ® Cook medical) was passed through the vocal cords under endoscopic vision. Over it, a 10Ch (2mm) endotracheal tube was advanced blindly[ 15 ]. Due to tracheal complications (as discussed later) subsequent animals (n = 15) were intubated using a laryngeal mask airway (LMA) ( ® V-gel: R2, Millpledge, Wingene, Belgium).…”

“…Data was analyzed using Prism for Windows version 5.0 (Graphpad software, San Diego, CA, USA). A power calculation based on our previous study (tensiometry results) suggested a repair group size of n = 6 would give 80% power (independent t-test)[ 15 ]. Data was checked for normality of distribution using a Kolmogorov-Smirnov test, then presented as a mean with SD or median and IQR.…”

“…Large animal models, particularly the rabbit have the advantage that they are more similar to human in terms of thoracic size, pulmonary function and growth rates[ 19 ]. Previously, we tested patch biocompatibility in a growing rabbit model of diaphragmatic hernia[ 15 ]. Rabbits are relatively inexpensive, easy to both house and handle and very fast growing, reaching full size by approximatively six months of age [ 20 ].…”