Repair of surgically created diaphragmatic defect in rat with use of a crosslinked porous collagen scaffold

Abstract

Large defects in congenital diaphragmatic hernia are closed by patch repair, which is associated with a high complication risk and reherniation rate. New treatment modalities are warranted. We evaluated the feasibility of using an acellular biodegradable collagen bioscaffold for a regenerative medicine approach to close a surgically created diaphragmatic defect in a rat model. Scaffold degradation, cellular ingrowth and regeneration of the diaphragm were studied. In 25 rats, a subcostal incision was made and one third of the right hemidiaphragm was resected. Crosslinked porous type I collagen scaffolds (Ø ~ 14 mm) were sutured into the lesion. Rats were sacrificed at 2, 4, 8, 12 or 24 weeks after scaffold implantation. Implants were evaluated macroscopically and (immuno)histologically. Survival after surgery was 88% with no evidence of reherniation. Histological examination showed that the collagen scaffold degraded slowly and new collagen, elastin and mesothelium were deposited. Blood vessels were observed primarily at the outer borders of the scaffold; their number gradually increased in time. Muscle fibres were found on the scaffold covering up to 10% of the defect. Macroscopically, adhesion of the scaffold to the liver was observed. Use of a collagen scaffold to close a surgically created diaphragmatic defect is feasible, with evidence of new tissue formation. The use of crosslinked collagen scaffolds allows targeted modification; e.g. addition of growth factors to further stimulate growth of muscle cells.

Collagen‐Vicryl scaffolds for reconstruction of the diaphragm in a large animal model

“…IGF1 may have diffused too rapidly and thus had a too short action period. In an earlier study we found that muscle regeneration is slow . More research on sustained growth factor release and dosage is recommended.…”

Heparinized collagen scaffolds with and without growth factors for the repair of diaphragmatic hernia

“…The use of porous collagen scaffolds has previously been shown feasible in a rat model for diaphragmatic hernia, 10 but muscle cell and blood vessel ingrowth were limited. Therefore, collagen scaffolds with heparin, HGF and VEGF were produced.…”

“…Surgery was performed as described previously. 10 In short, a right-sided diaphragmatic defect of approximately 12 mm in diameter was created, and a scaffold was implanted with an overlap of scaffold with respect to the diaphragm at the abdominal side. Four non-absorbable interrupted sutures (Prolene 6-0) and 2-5 absorbable interrupted sutures (Vicryl 5-0, Ethicon) were used around the perimeter of the scaffold to close the defect.…”

“…2 Moreover, it has been suggested that SIS is degraded too fast as the manufacturer indicated resorption of the material in 2 weeks. 7 In a previous study, 10 we have therefore used porous type I collagen bioscaffolds, strengthened by crosslinking, to close surgically created diaphragmatic defects in rats. Scaffold degradation and deposition of new collagen and of mesothelium were observed, and reherniations did not occur.…”

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

“…Furthermore, modifications in pore size and orientation can further enhance tissue ingrowth (Brouwer, Daamen, van Lochem, et al, ). Previously, radial pore‐orientated collagen scaffolds implanted into the diaphragm of rats showed promising results (Brouwer, Daamen, Reijnen, et al, ), although a slower degrading material was suggested to be necessary for larger animal models (Brouwer et al, ). Few of these materials are extensively tested preclinically, and available models are often only partly representative.…”