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Evaluation of the Biocompatibility of PLACL/Collagen Nanostructured Matrices with Cardiomyocytes as a Model for the Regeneration of Infarcted Myocardium
Authors:Shayanti Mukherjee  Jayarama Reddy Venugopal  Rajeswari Ravichandran  Seeram Ramakrishna  Michael Raghunath
Affiliation:1. Division of Bioengineering, 9 Engineering Drive 1, Block EA #03‐12, National University of Singapore, Singapore;2. HEM laboratory, Nanoscience and Nanotechnology Initiative, c/o Faculty of Engineering, Block E3‐05‐29, 2 Engineering Drive 3, National University of Singapore Singapore;3. Department of Mechanical Engineering, 9 Engineering Drive 1, Block EA, 07‐08, National University of Singapore, Singapore;4. Institute of Materials Research and Engineering, A‐Star, Singapore;5. Department of Biochemistry, Medical Drive Block MD7, #02‐03, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Abstract:Pioneering research suggests various modes of cellular therapeutics and biomaterial strategies for myocardial tissue engineering. Despite several advantages, such as safety and improved function, the dynamic myocardial microenvironment prevents peripherally or locally administered therapeutic cells from homing and integrating of biomaterial constructs with the infarcted heart. The myocardial microenvironment is highly sensitive due to the nanoscale cues that it exerts to control bioactivities, such as cell migration, proliferation, differentiation, and angiogenesis. Nanoscale control of cardiac function has not been extensively analyzed in the field of myocardial tissue engineering. Inspired by microscopic analysis of the ventricular organization in native tissue, a scalable in‐vitro model of nanoscale poly(L ‐lactic acid)‐co ‐poly(? ‐caprolactone)/collagen biocomposite scaffold is fabricated, with nanofibers in the order of 594 ± 56 nm to mimic the native myocardial environment for freshly isolated cardiomyocytes from rabbit heart, and the specifically underlying extracellular matrix architecture: this is done to address the specificity of the underlying matrix in overcoming challenges faced by cellular therapeutics. Guided by nanoscale mechanical cues provided by the underlying random nanofibrous scaffold, the tissue constructs display anisotropic rearrangement of cells, characteristic of the native cardiac tissue. Surprisingly, cell morphology, growth, and expression of an interactive healthy cardiac cell population are exquisitely sensitive to differences in the composition of nanoscale scaffolds. It is shown that suitable cell–material interactions on the nanoscale can stipulate organization on the tissue level and yield novel insights into cell therapeutic science, while providing materials for tissue regeneration.
Keywords:biomaterials  myocardial infarction  nanofibers  collagen  tissue engineering
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