Flexible shape-memory scaffold for minimally invasive delivery of functional tissues.

Despite great progress in engineering functional tissues for organ repair, including the heart, an invasive surgical approach is still required for their implantation. Here, we designed an elastic and microfabricated scaffold using a biodegradable polymer (poly(octamethylene maleate (anhydride) citrate)) for functional tissue delivery via injection. The scaffold's shape memory was due to the microfabricated lattice design. Scaffolds and cardiac patches (1 cm × 1 cm) were delivered through an orifice as small as 1 mm, recovering their initial shape following injection without affecting cardiomyocyte viability and function. In a subcutaneous syngeneic rat model, injection of cardiac patches was equivalent to open surgery when comparing vascularization, macrophage recruitment and cell survival. The patches significantly improved cardiac function following myocardial infarction in a rat, compared with the untreated controls. Successful minimally invasive delivery of human cell-derived patches to the epicardium, aorta and liver in a large-animal (porcine) model was achieved.

[1]  T. Borg,et al.  Structure and mechanics of healing myocardial infarcts. , 2005, Annual review of biomedical engineering.

[2]  Milica Radisic,et al.  Cardiac tissue engineering , 2013 .

[3]  I. Komuro,et al.  Implantation of cardiac progenitor cells using self-assembling peptide improves cardiac function after myocardial infarction. , 2010, Journal of molecular and cellular cardiology.

[4]  Larry Kedes,et al.  Survival and development of neonatal rat cardiomyocytes transplanted into adult myocardium. , 2002, Journal of molecular and cellular cardiology.

[5]  Andrew D McCulloch,et al.  Substrate stiffness affects the functional maturation of neonatal rat ventricular myocytes. , 2008, Biophysical journal.

[6]  Lisa E. Freed,et al.  Accordion-Like Honeycombs for Tissue Engineering of Cardiac Anisotropy , 2008, Nature materials.

[7]  Teruo Okano,et al.  Tissue engineered myoblast sheets improved cardiac function sufficiently to discontinue LVAS in a patient with DCM: report of a case , 2012, Surgery Today.

[8]  Kumaraswamy Nanthakumar,et al.  Biowire: a New Platform for Maturation of Human Pluripotent Stem Cell Derived Cardiomyocytes Pubmed Central Canada , 2022 .

[9]  M. Radisic,et al.  Biodegradable scaffold with built-in vasculature for organ-on-a-chip engineering and direct surgical anastomosis , 2016, Nature materials.

[10]  Milica Radisic,et al.  Biomaterial based cardiac tissue engineering and its applications , 2015, Biomedical materials.

[11]  G. Dusting,et al.  Neovascularization in an arterio-venous loop-containing tissue engineering chamber: role of NADPH oxidase , 2008, Journal of cellular and molecular medicine.

[12]  Madeline A. Lancaster,et al.  Cerebral organoids model human brain development and microcephaly , 2013, Nature.

[13]  M. Radisic,et al.  Engineering of Oriented Myocardium on Three-Dimensional Micropatterned Collagen-Chitosan Hydrogel , 2012, The International journal of artificial organs.

[14]  Chung-Dann Kan,et al.  Recipient age determines the cardiac functional improvement achieved by skeletal myoblast transplantation. , 2007, Journal of the American College of Cardiology.

[15]  Patrick Delafontaine,et al.  Multipotent human stromal cells improve cardiac function after myocardial infarction in mice without long-term engraftment. , 2007, Biochemical and biophysical research communications.

[16]  Hirotsugu Kurobe,et al.  Concise Review: Tissue‐Engineered Vascular Grafts for Cardiac Surgery: Past, Present, and Future , 2012, Stem cells translational medicine.

[17]  Paul A. Iaizzo.  Handbook of Cardiac Anatomy, Physiology, and Devices , 2005 .

[18]  G. Vunjak‐Novakovic,et al.  Macrophages Modulate Engineered Human Tissues for Enhanced Vascularization and Healing , 2014, Annals of Biomedical Engineering.

[19]  Boyang Zhang,et al.  Platform technology for scalable assembly of instantaneously functional mosaic tissues , 2015, Science Advances.

[20]  Ling Wu,et al.  Cartilage tissue engineering. , 2011, Endocrine development.

[21]  J. Omens,et al.  Stress and strain as regulators of myocardial growth. , 1998, Progress in biophysics and molecular biology.

[22]  Liping Tang,et al.  Synthesis and characterization of a biodegradable elastomer featuring a dual crosslinking mechanism. , 2010, Soft matter.

[23]  P. Doevendans,et al.  Human relevance of pre-clinical studies in stem cell therapy: systematic review and meta-analysis of large animal models of ischaemic heart disease. , 2011, Cardiovascular research.

[24]  P. Cockcroft,et al.  Handbook of Pig Medicine , 2007 .

[25]  Milica Radisic,et al.  Perfusable branching microvessel bed for vascularization of engineered tissues , 2012, Proceedings of the National Academy of Sciences.

[26]  Xuetao Sun,et al.  Biowire platform for maturation of human pluripotent stem cell-derived cardiomyocytes. , 2016, Methods.

[27]  M. Radisic,et al.  Highly Elastic and Moldable Polyester Biomaterial for Cardiac Tissue Engineering Applications. , 2016, ACS biomaterials science & engineering.

[28]  D. Karamichos.  Ocular Tissue Engineering: Current and Future Directions , 2015, Journal of functional biomaterials.

[29]  P. Mullis.  Cartilage and Bone Development and its Disorders , 2011 .

[30]  Amit Bandyopadhyay,et al.  Recent advances in bone tissue engineering scaffolds. , 2012, Trends in biotechnology.

[31]  Pál Pacher,et al.  Measurement of cardiac function using pressure–volume conductance catheter technique in mice and rats , 2008, Nature Protocols.

[32]  Shalom J. Wind,et al.  Responsive Biomaterials: Advances in Materials Based on Shape‐Memory Polymers , 2016, Advanced materials.

[33]  E. Tartour,et al.  Human embryonic stem cell-derived cardiac progenitors for severe heart failure treatment: first clinical case report. , 2015, European heart journal.

[34]  David J Mooney,et al.  Injectable preformed scaffolds with shape-memory properties , 2012, Proceedings of the National Academy of Sciences.

[35]  Ying Ge,et al.  Cardiac repair in a porcine model of acute myocardial infarction with human induced pluripotent stem cell-derived cardiovascular cells. , 2014, Cell stem cell.

[36]  Andreas Hess,et al.  Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts , 2006, Nature Medicine.

[37]  Thomas Eschenhagen,et al.  Cardiac tissue engineering: state of the art. , 2014, Circulation research.

[38]  H. Vandenburgh,et al.  Minimally invasive approach to the repair of injured skeletal muscle with a shape-memory scaffold. , 2014, Molecular therapy : the journal of the American Society of Gene Therapy.

[39]  Lila R Collins,et al.  Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts , 2007, Nature Biotechnology.

[40]  Mohammad Ariful Islam,et al.  Injectable Hydrogels for Cardiac Tissue Repair after Myocardial Infarction , 2015, Advanced science.

[41]  F. Guilak,et al.  Advanced Material Strategies for Tissue Engineering Scaffolds , 2009, Advanced materials.

[42]  Cory Swingen,et al.  Bioenergetic and Functional Consequences of Bone Marrow-Derived Multipotent Progenitor Cell Transplantation in Hearts With Postinfarction Left Ventricular Remodeling , 2007, Circulation.

[43]  Charles E. Murry,et al.  Human Embryonic Stem Cell-Derived Cardiomyocytes Regenerate Non-Human Primate Hearts , 2014, Nature.