title: The beneficial effects of deferred delivery on the efficiency of hydrogel therapy post myocardial infarction.
abstract: 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.
authors.affiliation: Cardiovascular Research Unit, Chris Barnard Division of Cardiothoracic Surgery, University of Cape Town, Department of Health Sciences, Cape Town 7925, South Africa.
authors.forename: Karen
authors.initials: K
authors.lastname: Kadner
authors.forename: Stephan
authors.initials: S
authors.lastname: Dobner
authors.forename: Thomas
authors.initials: T
authors.lastname: Franz
authors.forename: Deon
authors.initials: D
authors.lastname: Bezuidenhout
authors.forename: Mazin S
authors.initials: MS
authors.lastname: Sirry
authors.forename: Peter
authors.initials: P
authors.lastname: Zilla
authors.forename: Neil H
authors.initials: NH
authors.lastname: Davies
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D016503:Drug Delivery Systems; D006321:Heart / Q000187:drug effects; D006801:Humans; D020100:Hydrogels / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels; D011092:Polyethylene Glycols