A novel two-component, expandable bioadhesive for exposed defect coverage: Applicability to prenatal procedures

Abstract

Background/purpose: We sought to test select properties of a novel, expandable bioadhesive composite that allows for enhanced adhesion control in liquid environments.

Methods: Rabbit fetuses (n = 23) underwent surgical creation of spina bifida on gestational day 22-25 (term 32-33 days). Defects were immediately covered with a two-component tough adhesive consisting of a hydrogel made of a double network of ionically crosslinked alginate and covalently crosslinked polyacrylamide linked to a bridging chitosan polymer adhesive. Animals were euthanized prior to term for different analyses, including hydraulic pressure testing.

Results: Hydrogels remained adherent in 70% (16/23) of the recovered fetuses and in all of the last 14 fetuses as the procedure was optimized. Adherent hydrogels showed a median two-fold (IQR: 1.7-2.4) increase in area at euthanasia, with defect coverage confirmed by ultrasound and histology. The median maximum pressure to repair failure was 15 mmHg (IQR: 7.8-55.3), exceeding reported neonatal cerebrospinal fluid pressures.

Conclusions: This novel bioadhesive composite allows for selective, stable attachment of an alginate-polyacrylamide hydrogel to specific areas of the spina bifida defect in a fetal rabbit model, while the hydrogel expands with the defect over time. It could become a valuable alternative for the prenatal repair of spina bifida and possibly other congenital anomalies.

Type of study: N/A (animal and laboratory study).

Level of evidence: N/A (animal and laboratory study).

Keywords: Bioadhesive; Biocomposite; Fetal surgery; Surgical coverage; Tough adhesive; Wound repair.

Figure 1:

Diagram depicting the composite adhesive system as it is applied to fetal tissue. The top component represents the hydrogel made of a dissipative matrix consisting of ionically (calcium-based) crosslinked alginate and covalently crosslinked polyacrylamide (PAAM). The middle layer represents the bridging chitosan polymer adhesive.

Figure 2:

Gross views of: A) the exposed hindlimbs and rump of a rabbit fetus prior to creation of a spina bifida defect; B) completed spina bifida defect; C) completed application of the composite adhesive system covering the defect; D) adherent composite covering the spina bifida defect after euthanasia.

Figure 3:

High-frequency ultrasound was used to demonstrate adhesion between the hydrogel and fetal tissue in both operated (2D: upper left; 3D: lower left) and time-zero (2D: upper right, 3D: lower right) fetuses after euthanasia. In the 3D ultrasound images, 3D renderings of different structures were created based upon relative echogenicity as follows: the hypoechoic hydrogel is rendered in blue, the hypoechoic defect is rendered in red, and a layer of hyperechoic tissue interface between the hydrogel and defect is rendered in green.

Figure 4:

Representative histological images showing: (left) integration of the hydrogel (purple), chitosan bioadhesive (bright pink), and fetal tissue, with interdigitation of the hydrogel-adhesive composite into the fetal tissue; (right) lack of adhesion of the hydrogel to the underlying flattened spinal cord typical of spina bifida. (H&E, 100x).

Figure 5:

Maximum pressure to repair failure on hydraulic testing in operated (median 15.0 mmHg; IQR: 7.8–55.3) and time-zero (median 31.2 mmHg; IQR: 10.4–97.4) fetuses. These differences were not statistically significant (p=0.5).