Comparison of physical and biological properties of CardioCel® with commonly used bioscaffolds

Abstract

OBJECTIVES: Durability of bioscaffolds cross-linked with glutaraldehyde and used in cardiovascular surgery is limited by biomechanical instability, calcification and reduced biocompatibility. This study compares CardioCel V R , a bovine pericardial scaffold engineered via the ADAPT V R process to ensure optimized biostability and biocompatibility, with the commonly used bioscaffolds. METHODS:Bovine pericardial scaffolds, cross-linked with 0.6% glutaraldehyde (XenoLogiX TM , PeriGuard V R ), dye-mediated photo-oxidized (PhotoFix TM ) and a non-crosslinked porcine scaffold (CorMatrix V R ), were compared with CardioCel (decellularized, cross-linked with 0.05% monomeric glutaraldehyde, detoxified) by thermal stability and mechanical tests. Biocompatibility and calcification were assessed in a juvenile subcutaneous rat model at 6 and 12 weeks. RESULTS:CardioCel displayed significantly higher (P < 0.01) cross-link stability (77.99 ± 0.64 C) than CorMatrix (57.88 ± 0.22 C) and PhotoFix (53.96 ± 0.41 C). Tensile strength of CardioCel (8.31 ± 3.36 MPa) was comparable with XenoLogiX (11.00 ± 5.43 MPa, P = 0.734), PeriGuard (16.44 ± 6.69 MPa, P = 0.136), PhotoFix (7.10 ± 6.11, P = 0.399) and CorMatrix (9.75 ± 2.61, P = 0.204). XenoLogiX and PeriGuard recorded the highest Young's modulus (67.01 ± 30.36 vs 95.67 ± 45.91 MPa), while CardioCel (50.21 ± 19.92 MPa) was comparable with CorMatrix (36.78 ± 10.47 MPa, P = 0.204) and PhotoFix (33.50 ± 10.24, P = 0.399). CorMatrix displayed a significantly (P < 0.05) greater stiffness (4.74 ± 0.77 MPa) at 10% strain than PeriGuard (3.73 ± 1.79 MPa), PhotoFix (1.59 ± 0.40 MPa) and CardioCel (3.39 ± 0.83 MPa). Differences in extractable calcium did not reach significance; however, the inorganic phosphorus content of PhotoFix (21.3 ± 9.0 mg/mg) was higher than CardioCel (11.35 ± 0.76 mg/mg, P = 0.004) or PeriGuard (10.7 ± 2.18 mg/mg, P = 0.002) at 12 weeks. CardioCel underwent a typical mild host-graft response with fibroblast infiltration and remodelling. Foreign body reactions were visible in both XenoLogiX and PeriGuard, with isolated fibroblast infiltration. PhotoFix showed severe inflammation and 2 implants were completely degraded at 12 weeks.CONCLUSIONS: CardioCel demonstrated optimized physical properties, minimal mineralization potential and superior biocompatibility. These results may benefit the long-term performance of this bioscaffold for cardiovascular surgery. The favourable characteristics of the comparator products were counterbalanced by less desirable features that may have negative implications on durability and performance when used in cardiovascular procedures.

Promoting Cardiac Regeneration and Repair Using Acellular Biomaterials

“…Degradation may allow hydrogels to provide bioactive effects and then degrade after they confer regenerative effects but long-term retention of materials in EIR may allow for long-term support of the ventricle (Hoffman, 2002;Tous et al, 2011;Mewhort et al, 2016Mewhort et al, , 2017Pattar et al, 2019a). On the other hand, retention of foreign material may increase likelihood of inflammation or calcification (Manji et al, 2006;Witt et al, 2013;Rosario-Quinones et al, 2015;Neethling et al, 2018).…”

“…Prior to assessing bioactive components, the physical properties of biomaterials can be examined. Uniaxial tensile tests include pulling specimens apart until failure can be used to assess Young's modulus and tensile strength patch biomaterials (Neethling et al, 2018). Tensile strength can also be used to assess robustness for suturing.…”

Acellular Extracellular Matrix Bioscaffolds for Cardiac Repair and Regeneration

“…Recently, in-vivo characterization of calcification compared CardioCel ® to Peri-Guard ® , PhotoFix TM , and CorMatrix ® , using a juvenile subcutaneous rat model. While a significant difference in calcification was not seen across groups, the extractable calcium level of CardioCel ® was similar to that of PhotoFix TM , 0.45 and 0.44 μg/mg tissue, respectively, and was lower than Peri-Guard ® , 0.85 μg/mg tissue (Neethling et al, 2018). Variable outcomes have been shown in-vivo; CardioCel ® displayed promising endothelialization and remodeling in the native cardiac ECM environment and resistance to calcification in a chronic juvenile sheep model of pulmonary valve and mitral valve reconstruction (Brizard et al, 2014).…”

“…CardioCel ® (Admedus Limited, Australia), is a BP-ECM bioscaffold that is cross-linked using a proprietary fixation technique known as ADAPT ® (Pavy et al, 2017). Although this technique utilizes glutaraldehyde fixation, it employs a low concentration of glutaraldehyde (0.05%) compared to other clinical standards such as Peri-Guard (0.6%) (Neethling et al, 2018). Additionally, CardioCel ® ADAPT ® involves an additional detoxification step to remove any traces of glutaraldehyde (Pavy et al, 2017).…”

Tissue Engineered Materials in Cardiovascular Surgery: The Surgeon's Perspective

“…Although a promising concept, acellular porcine small intestinal submucosa patches can also provoke an inflammatory response and can demonstrate early degeneration or calcifications leading to valve insufficiency when used for aortic valve repair (63,64), or aneurysm formation when used for aortic reconstruction in pediatric patients (65). Decellularized bovine pericardium, though treated with low concentrations of glutaraldehyde (66), was found to be safe and effective in the mid-term when used for patch repair of complex congenital cardiac anomalies (40) and exhibited greater strain resistance compared to porcine small intestinal submucosa (67). Nevertheless, the possibility of calcification of the decellularized bovine pericardium has also been raised recently (68) and the quest for the "ideal" tissue engineered material continues.…”