Joseph C. Walker

Bio: Joseph C. Walker is an academic researcher from University of California, San Francisco. The author has contributed to research in topics: Left Ventricular Aneurysm & Dor procedure. The author has an hindex of 9, co-authored 14 publications receiving 752 citations. Previous affiliations of Joseph C. Walker include University of California, Berkeley.

Theoretical impact of the injection of material into the myocardium: a finite element model simulation.

Abstract: Background— To treat cardiac injuries created by myocardial infarcts, current approaches seek to add cells and/or synthetic extracellular matrices to the damaged ventricle to restore function. Because definitive myocardial regeneration remains undemonstrated, we propose that cardiac changes observed from implanted materials may result from altered mechanisms of the ventricle. Methods and Results— We exploited a validated finite element model of an ovine left ventricle with an anteroapical infarct to examine the short-term effect of injecting material to the left ventricular wall. The model’s mesh and regional material properties were modified to simulate expected changes. Three sets of simulations were run: (1) single injection to the anterior border zone; (2) therapeutic multiple border zone injections; and (3) injection of material to the infarct region. Results indicate that additions to the border zone decrease end-systolic fiber stress proportionally to the fractional volume added, with stiffer mater...

MRI-based finite-element analysis of left ventricular aneurysm

Abstract: Tagged MRI and finite-element (FE) analysis are valuable tools in analyzing cardiac mechanics. To determine systolic material parameters in three-dimensional stress-strain relationships, we used ta...

The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) Trial: First Randomized Placebo-Controlled Study of Myoblast Transplantation

Abstract: Background— Phase I clinical studies have demonstrated the feasibility of implanting autologous skeletal myoblasts in postinfarction scars. However, they have failed to determine whether this procedure was functionally effective and arrhythmogenic. Methods and Results— This multicenter, randomized, placebo-controlled, double-blind study included patients with left ventricular (LV) dysfunction (ejection fraction ≤35%), myocardial infarction, and indication for coronary surgery. Each patient received either cells grown from a skeletal muscle biopsy or a placebo solution injected in and around the scar. All patients received an implantable cardioverter-defibrillator. The primary efficacy end points were the 6-month changes in global and regional LV function assessed by echocardiography. The safety end points comprised a composite index of major cardiac adverse events and ventricular arrhythmias. Ninety-seven patients received myoblasts (400 or 800 million; n=33 and n=34, respectively) or the placebo (n=30). ...

Effect of Injectable Alginate Implant on Cardiac Remodeling and Function After Recent and Old Infarcts in Rat

Abstract: Background—Adverse cardiac remodeling and progression of heart failure after myocardial infarction are associated with excessive and continuous damage to the extracellular matrix. We hypothesized that injection of in situ–forming alginate hydrogel into recent and old infarcts would provide a temporary scaffold and attenuate adverse cardiac remodeling and dysfunction. Methods and Results—We developed a novel absorbable biomaterial composed of calcium-crosslinked alginate solution, which displays low viscosity and, after injection into the infarct, undergoes phase transition into hydrogel. To determine the outcome of the biomaterial after injection, calcium-crosslinked biotin-labeled alginate was injected into the infarct 7 days after anterior myocardial infarction in rat. Serial histology studies showed in situ formation of alginate hydrogel implant, which occupied up to 50% of the scar area. The biomaterial was replaced by connective tissue within 6 weeks. Serial echocardiography studies before and 60 days after injection showed that injection of alginate biomaterial into recent (7 days) infarct increased scar thickness and attenuated left ventricular systolic and diastolic dilatation and dysfunction. These beneficial effects were comparable and sometimes superior to those achieved by neonatal cardiomyocyte transplantation. Moreover, injection of alginate biomaterial into old myocardial infarction (60 days) increased scar thickness and improved systolic and diastolic dysfunction. Conclusions—We show for the first time that injection of in situ–forming, bioabsorbable alginate hydrogel is an effective acellular strategy that prevents adverse cardiac remodeling and dysfunction in recent and old myocardial infarctions in rat. (Circulation. 2008;117:1388-1396.)

Biomaterials in cardiac tissue engineering: Ten years of research survey

Abstract: Driven by enormous clinical need, myocardial tissue engineering has become a prime focus of research within the field of tissue engineering. Myocardial tissue engineering combines isolated functional cardiomyocytes and a biodegradable or nondegradable biomaterial to repair diseased heart muscle. The challenges in heart muscle engineering include cell related issues (such as scale up in a short timeframe, efficiency of cell seeding or cell survival rate, and immune rejection), the design and fabrication of myocardial tissue engineering substrates, and the engineering of tissue constructs in vitro and in vivo. Several approaches have been put forward, and a number of models combining various polymeric biomaterials, cell sources and bioreactors have been developed in the last 10 years for myocardial tissue engineering. This review provides a comprehensive update on the biomaterials, as well as cells and biomimetic systems, used in the engineering of the cardiac muscle. The article is organized as follows. A historic perspective of the evolution of cardiac medicine and emergence of cardiac tissue engineering is presented in the first section. Following a review on the cells used in myocardial tissue engineering (second section), the third section presents a review on biomaterials used in myocardial tissue engineering. This section starts with an overview of the development of tissue engineering substrates and goes on to discuss the selection of biomaterials and design of solid and porous substrates. Then the applications of a variety of biomaterials used in different approaches of myocardial tissue engineering are reviewed in great detail, and related issues and topics that remain challenges for the future progress of the field are identified at the end of each subsection. This is followed by a brief review on the development of bioreactors (fourth section), which is an important achievement in the field of myocardial tissue engineering, and which is also related to the biomaterials developed. At the end of this article, the major achievements and remaining challenges are summarized, and the most promising paradigm for the future of heart muscle tissue engineering is proposed (fifth section).