Rebecca L. Braden

Bio: Rebecca L. Braden is an academic researcher from University of California, San Diego. The author has contributed to research in topics: Self-healing hydrogels & Decellularization. The author has an hindex of 17, co-authored 24 publications receiving 1183 citations. Previous affiliations of Rebecca L. Braden include University of Montana & University of California, Berkeley.

Safety and Efficacy of an Injectable Extracellular Matrix Hydrogel for Treating Myocardial Infarction

Abstract: New therapies are needed to prevent heart failure after myocardial infarction (MI). As experimental treatment strategies for MI approach translation, safety and efficacy must be established in relevant animal models that mimic the clinical situation. We have developed an injectable hydrogel derived from porcine myocardial extracellular matrix as a scaffold for cardiac repair after MI. We establish the safety and efficacy of this injectable biomaterial in large- and small-animal studies that simulate the clinical setting. Infarcted pigs were treated with percutaneous transendocardial injections of the myocardial matrix hydrogel 2 weeks after MI and evaluated after 3 months. Echocardiography indicated improvement in cardiac function, ventricular volumes, and global wall motion scores. Furthermore, a significantly larger zone of cardiac muscle was found at the endocardium in matrix-injected pigs compared to controls. In rats, we establish the safety of this biomaterial and explore the host response via direct injection into the left ventricular lumen and in an inflammation study, both of which support the biocompatibility of this material. Hemocompatibility studies with human blood indicate that exposure to the material at relevant concentrations does not affect clotting times or platelet activation. This work therefore provides a strong platform to move forward in clinical studies with this cardiac-specific biomaterial that can be delivered by catheter.

Enzyme-Responsive Nanoparticles for Targeted Accumulation and Prolonged Retention in Heart Tissue after Myocardial Infarction.

Abstract: A method for targeting to and retaining intravenously injected nanoparticles at the site of acute myocardial infarction in a rat model is described. Enzyme-responsive peptide-polymer amphiphiles are assembled as spherical micellar nanoparticles, and undergo a morphological transition from spherical-shaped, discrete materials to network-like assemblies when acted upon by matrix metalloproteinases (MMP-2 and MMP-9), which are up-regulated in heart tissue post-myocardial infarction.

Oxime cross-linked injectable hydrogels for catheter delivery

Abstract: Catheter delivery of therapeutic materials is important for developing minimally invasive treatment approaches. However, the majority of injectable materials gel rapidly upon mixing and/or heating to body temperature. The application of an oxime cross-linked hydrogel system is demonstrated. The system has a broad range of tunable gelation rates, is capable of injection through a catheter, and exhibits rapid gelation upon injection into tissue.

Remodelling the extracellular matrix in development and disease.

Abstract: The extracellular matrix (ECM) is a highly dynamic structure that is present in all tissues and continuously undergoes controlled remodelling. This process involves quantitative and qualitative changes in the ECM, mediated by specific enzymes that are responsible for ECM degradation, such as metalloproteinases. The ECM interacts with cells to regulate diverse functions, including proliferation, migration and differentiation. ECM remodelling is crucial for regulating the morphogenesis of the intestine and lungs, as well as of the mammary and submandibular glands. Dysregulation of ECM composition, structure, stiffness and abundance contributes to several pathological conditions, such as fibrosis and invasive cancer. A better understanding of how the ECM regulates organ structure and function and of how ECM remodelling affects disease progression will contribute to the development of new therapeutics.

Biowire: a platform for maturation of human pluripotent stem cell-derived cardiomyocytes

Abstract: Directed differentiation protocols enable derivation of cardiomyocytes from human pluripotent stem cells (hPSCs) and permit engineering of human myocardium in vitro However, hPSC-derived cardiomyocytes are reflective of very early human development, limiting their utility in the generation of in vitro models of mature myocardium Here we describe a platform that combines three-dimensional cell cultivation with electrical stimulation to mature hPSC-derived cardiac tissues We used quantitative structural, molecular and electrophysiological analyses to explain the responses of immature human myocardium to electrical stimulation and pacing We demonstrated that the engineered platform allows for the generation of three-dimensional, aligned cardiac tissues (biowires) with frequent striations Biowires submitted to electrical stimulation had markedly increased myofibril ultrastructural organization, elevated conduction velocity and improved both electrophysiological and Ca(2+) handling properties compared to nonstimulated controls These changes were in agreement with cardiomyocyte maturation and were dependent on the stimulation rate

The Smart Drug Delivery System and Its Clinical Potential

Abstract: With the unprecedented progresses of biomedical nanotechnology during the past few decades, conventional drug delivery systems (DDSs) have been involved into smart DDSs with stimuli-responsive characteristics. Benefiting from the response to specific internal or external triggers, those well-defined nanoplatforms can increase the drug targeting efficacy, in the meantime, reduce side effects/toxicities of payloads, which are key factors for improving patient compliance. In academic field, variety of smart DDSs have been abundantly demonstrated for various intriguing systems, such as stimuli-responsive polymeric nanoparticles, liposomes, metals/metal oxides, and exosomes. However, these nanoplatforms are lack of standardized manufacturing method, toxicity assessment experience, and clear relevance between the pre-clinical and clinical studies, resulting in the huge difficulties to obtain regulatory and ethics approval. Therefore, such relatively complex stimulus-sensitive nano-DDSs are not currently approved for clinical use. In this review, we highlight the recent advances of smart nanoplatforms for targeting drug delivery. Furthermore, the clinical translation obstacles faced by these smart nanoplatforms have been reviewed and discussed. We also present the future directions and perspectives of stimuli-sensitive DDS in clinical applications.

Functional and Biomimetic Materials for Engineering of the Three-Dimensional Cell Microenvironment

Abstract: The cell microenvironment has emerged as a key determinant of cell behavior and function in development, physiology, and pathophysiology. The extracellular matrix (ECM) within the cell microenvironment serves not only as a structural foundation for cells but also as a source of three-dimensional (3D) biochemical and biophysical cues that trigger and regulate cell behaviors. Increasing evidence suggests that the 3D character of the microenvironment is required for development of many critical cell responses observed in vivo, fueling a surge in the development of functional and biomimetic materials for engineering the 3D cell microenvironment. Progress in the design of such materials has improved control of cell behaviors in 3D and advanced the fields of tissue regeneration, in vitro tissue models, large-scale cell differentiation, immunotherapy, and gene therapy. However, the field is still in its infancy, and discoveries about the nature of cell–microenvironment interactions continue to overturn much earl...

Adaptable Hydrogel Networks with Reversible Linkages for Tissue Engineering

Abstract: Adaptable hydrogels have recently emerged as a promising platform for three-dimensional (3D) cell encapsulation and culture. In conventional, covalently crosslinked hydrogels, degradation is typically required to allow complex cellular functions to occur, leading to bulk material degradation. In contrast, adaptable hydrogels are formed by reversible crosslinks. Through breaking and re-formation of the reversible linkages, adaptable hydrogels can be locally modified to permit complex cellular functions while maintaining their long-term integrity. In addition, these adaptable materials can have biomimetic viscoelastic properties that make them well suited for several biotechnology and medical applications. In this review, an overview of adaptable-hydrogel design considerations and linkage selections is presented, with a focus on various cell-compatible crosslinking mechanisms that can be exploited to form adaptable hydrogels for tissue engineering.