The beneficial effects of deferred delivery on the efficiency of hydrogel therapy post myocardial infarction

TY - JOUR

T1 - The beneficial effects of deferred delivery on the efficiency of hydrogel therapy post myocardial infarction

AU - Kadner, Karen

AU - Dobner, Stephan

AU - Franz, Thomas

AU - Bezuidenhout, Deon

AU - Sirry, Mazin S

AU - Zilla, Peter

AU - Davies, Neil H

N1 - Copyright © 2011 Elsevier Ltd. All rights reserved.

PY - 2012/3

Y1 - 2012/3

N2 - Biomaterials are increasingly being investigated as a means of reducing stress within the ventricular wall of infarcted hearts and thus attenuating pathological remodelling and loss of function. In this context, we have examined the influence of timing of delivery on the efficacy of a polyethylene glycol hydrogel polymerised with an enzymatically degradable peptide sequence. Delivery of the hydrogel immediately after infarct induction resulted in no observable improvements, but a delay of one week in delivery resulted in significant increases in scar thickness and fractional shortening, as well as reduction in end-systolic diameter against saline controls and immediately injected hydrogel at both 2 and 4 weeks post-infarction (p < 0.05). Hydrogels injected at one week were degraded significantly slower than those injected immediately and this may have played a role in the differing outcomes. The hydrogel assumed markedly different morphologies at the two time points having either a fibrillar or bulky appearance after injection immediately or one week post-infarction respectively. We argue that the different morphologies result from infarction induced changes in the cardiac structure and influence the degradability of the injectates. The results indicate that timing of delivery is important and that very early time points may not be beneficial.

AB - Biomaterials are increasingly being investigated as a means of reducing stress within the ventricular wall of infarcted hearts and thus attenuating pathological remodelling and loss of function. In this context, we have examined the influence of timing of delivery on the efficacy of a polyethylene glycol hydrogel polymerised with an enzymatically degradable peptide sequence. Delivery of the hydrogel immediately after infarct induction resulted in no observable improvements, but a delay of one week in delivery resulted in significant increases in scar thickness and fractional shortening, as well as reduction in end-systolic diameter against saline controls and immediately injected hydrogel at both 2 and 4 weeks post-infarction (p < 0.05). Hydrogels injected at one week were degraded significantly slower than those injected immediately and this may have played a role in the differing outcomes. The hydrogel assumed markedly different morphologies at the two time points having either a fibrillar or bulky appearance after injection immediately or one week post-infarction respectively. We argue that the different morphologies result from infarction induced changes in the cardiac structure and influence the degradability of the injectates. The results indicate that timing of delivery is important and that very early time points may not be beneficial.

KW - Animals

KW - Biocompatible Materials/chemistry

KW - Drug Delivery Systems

KW - Heart/drug effects

KW - Humans

KW - Hydrogels/chemistry

KW - Male

KW - Myocardial Infarction/drug therapy

KW - Polyethylene Glycols/chemistry

KW - Rats

KW - Rats, Wistar

KW - Ventricular Remodeling/drug effects

U2 - 10.1016/j.biomaterials.2011.11.031

DO - 10.1016/j.biomaterials.2011.11.031

M3 - SCORING: Journal article

C2 - 22153866

VL - 33

SP - 2060

EP - 2066

JO - BIOMATERIALS

JF - BIOMATERIALS

SN - 0142-9612

IS - 7

ER -