Lysine‐enhanced glutaraldehyde crosslinking of collagenous biomaterials

Simionescu, Anca A.; Simionescu, Dan T.; Deac, Radu

doi:10.1002/jbm.820251207

Cited by 48 publications

(25 citation statements)

References 20 publications

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“…Collagen scaffolds were treated with glutaraldehyde, a known protein cross-linker, 23 and PGG, a compound known to interact with proline-rich proteins such as collagen. 24 Samples were then tested in vitro for resistance to collagenase, mechanical properties, and thermal denaturation characteristics.…”

Section: Cross-linking Evaluationmentioning

confidence: 99%

Stabilized Collagen Scaffolds for Heart Valve Tissue Engineering

Tedder

Liao

Weed

et al. 2009

Tissue Engineering Part A

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Scaffolds for heart valve tissue engineering must function immediately after implantation but also need to tolerate cell infiltration and gradual remodeling. We hypothesized that moderately cross-linked collagen scaffolds would fulfill these requirements. To test our hypothesis, scaffolds prepared from decellularized porcine pericardium were treated with penta-galloyl glucose (PGG), a collagen-binding polyphenol, and tested for biodegradation, biaxial mechanical properties, and in vivo biocompatibility. For controls, we used un-cross-linked scaffolds and glutaraldehyde-treated scaffolds. Results confirmed complete pericardium decellularization and the ability of scaffolds to encourage fibroblast chemotaxis and to aid in creation of anatomically correct valve-shaped constructs. Glutaraldehyde cross-linking fully stabilized collagen but did not allow for tissue remodeling and calcified when implanted subdermally in rats. PGG-treated collagen was initially resistant to collagenase and then degraded gradually, indicating partial stabilization. Moreover, PGG-treated pericardium exhibited excellent biaxial mechanical properties, did not calcify in vivo, and supported infiltration by host fibroblasts and subsequent matrix remodeling. In conclusion, PGG-treated acellular pericardium is a promising scaffold for heart valve tissue engineering.

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Section: Cross-linking Evaluationmentioning

confidence: 99%

Stabilized Collagen Scaffolds for Heart Valve Tissue Engineering

Tedder

Liao

Weed

et al. 2009

Tissue Engineering Part A

Self Cite

123

111

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“…The possible range of such alternative crosslinks is relatively broad, including the bridging of activated carboxyl groups with diamines 2,11 and the use of glutaraldehyde for crosslinking amino groups of the tissue with unreacted amines of equally introduced aliphatic diamines. 12 Since glutaraldehyde-treated tissue containing additional diamine bridges was shown to nearly eliminate graft-specific antibody induction, 2,11 we chose a similar but purely amino group-dependent crosslink augmentation 12 used in previous rat studies. 7,8 The aim of the present study was (1) to confirm in a sheep circulatory model that the mitigating effect of higher glutaraldehyde concentrations on tissue calcification can be significantly enhanced by the introduction of additional diamine bridges, and (2) to correlate crosslink density with bioprosthetic mineralization.…”

Section: Introductionmentioning

confidence: 99%

Diamine extension of glutaraldehyde crosslinks mitigates bioprosthetic aortic wall calcification in the sheep model

Zilla

Bezuidenhout

Weissenstein

et al. 2001

J. Biomed. Mater. Res.

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We previously have been able to show that fixation at increasing concentrations of glutaraldehyde (GA) leads to mitigated rather than facilitated tissue calcification. The purpose of the present study was to introduce additional crosslinks and provide evidence that crosslink density may be an underlying inhibitory principle. Entire aortic roots were chosen to verify the concept on the challenging aortic wall tissue. Porcine aortic roots were crosslinked with 0.2% GA, 3%GA, and 3% GA containing an interim step that introduced diamine bridges. Crosslink efficiency was determined on the basis of shrinkage temperature (SrT degrees ), resistance to protease digestion (RPD), residual amine analysis (RA), and tensile modulus (E(10)). Calcium levels, calcification patterns, and inflammation were assessed after 6 and 24 weeks of implantation in a sheep circulatory model. Crosslink efficiency in aortic wall tissue was moderately affected by increasing the fixative concentration from 0.2% GA to 3% GA (SrT degrees from 85.7 degrees +/- 0.3 degrees to 87.5 degrees +/- 0.3 degrees C, p < 0.002; RPD from 24.2 +/- 1.2 to 29.1 +/- 0.7%, p < 0.003; RA from 0.069 +/- 0.004 to 0.058 +/- 0.003 micromol/mg, p < 0.03, and E(10) from 1.9 +/- 0.11 to 2.94 +/- 0.34 MPa, p < 0.01), but it was distinctly enhanced when diamine bridges were introduced (SrT degrees from 87.5 degrees +/- 0.3 degrees to 93.4 degrees +/- 0.3 degrees C, p << 0.0001; RPD from 29.1 +/- 0.7 to 68.4 +/- 1.8%, p << 0.0001; and E(10) from 2.94 +/- 0.34 to 6.80 +/- 0.61 MPa, p < 0.0003). Aortic wall calcification was reduced significantly by increasing the GA concentration from 0.2 to 3% [37.8%, p = 0.076 (6 weeks) and 34.0%, p = 0.008 (24 weeks)] and further reduced by the introduction of additional diamine [84.0%, p = 0.006 (6 weeks) and 29.8%, p = 0.037 (24 weeks)]. The combined effect of increased GA concentration plus an interim diamine step on aortic wall tissue resulted in a 90% and 53.7% reduction of calcification after 6 weeks and 24 weeks, respectively. The correlation coefficients between calcification and SrT degrees, RDP, and E(10) was -0.9767, -0.9460, and -0.9740, respectively (6 weeks). The inflammatory host reaction regularly found in 0.2% fixed tissue was practically abolished through the introduction of diamine bridges. Our study demonstrated a distinct correlation between the mitigation of aortic wall calcification and three parameters used to assess crosslink density.

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“…As reported above, DSC studies showed there was a drastic decrease in the shrinkage temperature of oxazolidine tanned deaminated hide powder compared to oxazolidine tanned raw hide powder. Earlier reports hypothesized that this was due to cross-links being formed between the -NH 2 groups of lysine and the aldehydic reagents through the Mannich reaction resulting in inter fibril cross-links [3,30]. Amino acid analysis, however, did not show any difference in the amount of lysine or hydroxylysine both before and after tanning with oxazolidines, showing that there was no irreversible binding between these amino acids and oxazolidines.…”

Section: Amino Acid Analysismentioning

confidence: 77%