Engineered Biomaterials for Cardiac Repair and Disease Models

Biomaterials can be used in the treatment of cardiac disease (e.g., myocardial infarction (MI)) through the delivery of mechanical and biological signals that influence cardiac function, as well as in the development of in vitro models to better understand and evaluate therapies for cardiac treatment. Our efforts have primarily been in the development and application of injectable hydrogels (e.g., shear-thinning and self-healing) to alter the left-ventricular remodeling that occurs after MI, through approaches that target increased stress in the myocardial wall, proteolytic degradation of the extracellular matrix, vascularization, and the replacement of lost cardiomyocytes. This has included the delivery of protease inhibitors, extracellular vesicles, and miRNA and our work has spun off into several start-up companies. Recent work is focused on developing nanoparticles for controlled drug delivery after MI and biofabrication platforms for cardiac disease models. 

We collaborate extensively on this work with clinicians and basic/clinical scientists, including Dr. Frank Spinale (U South Carolina), Dr. Pavan Atluri (UPenn), Dr. Al Sinusas (Yale), Dr. Robert Gorman (UPenn), Dr. Leslie Leinwand (CU Boulder).


Musculoskeletal Therapies and Models of Injury and Disease

Biomaterials can be useful in the engineering of new musculoskeletal tissues or in the delivery of therapeutics to alter disease progression.  Our efforts have focused on therapies for the repair of cartilaginous tissues (e.g., articular cartilage, knee meniscus) through the engineering of cellular microenvironments that control cartilage formation or through the use of acellular biomaterials that recruit cells for endogenous repair. As examples, for cartilage tissue engineering we have engineered hydrogels to replicate features important during cartilage development to mediate mesenchymal stromal cell chondrogenesis (e.g., cadherin interactions) and for meniscal repair we have delivered factors to soften nuclei to support their recruitment into engineered fibrous scaffolds. Recent work involves the use of bioprinting to guide cell and tissue anisotropy and the development of in vitro platforms to better understand musculoskeletal disease (e.g., osteoarthritis).

We collaborate on these projects with engineers, basic scientists, and clinicians, including Dr. Robert Mauck (UPenn), Dr. James Carey (UPenn), Dr. Su-Chin Heo (UPenn), Dr. Sarah Gullbrand (UPenn), Dr. Lin Han (Drexel), Dr. Mike Zuscik (CU Anschutz).


Engineering Granular Hydrogels

Granular hydrogels are fabricated through the packing of hydrogel microparticles (or microgels) and exhibit important properties for biomedicine, including injectability via shear-thinning and self-healing properties due to microgel flow, inherent porosity for cell invasion due to the space between particles after jamming, and potential material diversity through changes in the mixing of microgel populations or control over microgel degradation, size, and shape. Our group has leveraged these important properties and explored granular hydrogels for the repair of tissues (e.g., cardiac), for tissue engineering (e.g., cartilage), and for 3D extrusion printing. Recent work has investigated how particle shape influences particle packing/pore geometry/cell invasion, developed new approaches to mix microgels and cellular spheroids together into living granular materials for tissue engineering, and used granular materials to guide organoid growth.

We collaborate with other engineers on improved methods to fabricate microgels and applications that leverage microgel technologies, including Dr. David Issadore (UPenn), Dr. Daeyeon Lee (UPenn), Dr. Kristi Anseth (CU Boulder).


Advances in Biofabrication Methods

Biofabrication involves the use of automated fabrication technologies to organize materials and cells into desired configurations that can be useful for the engineering of tissues or the development of various models of injury and disease. Common methods include the use of extrusion bioprinting to process typically hydrogel materials with cells into 3D shapes and lithography (e.g., digital light processing (DLP)) where light controls the spatial crosslinking of resins, typically in a layer-by-layer manner. Our work has focused on the development of new printing methods that can expand the range of materials useful in 3D printing, as well as the development of new inks and resins to expand the properties available in printed constructs. Recent work involves the advancement of volumetric additive manufacturing for the processing of hydrogels, as well as the development of new hydrogel resins with controlled properties (e.g., toughness, degradation) for DLP printing.

We collaborate with a number of other investigators on these approaches, including Dr. Bob McLeod (CU Boulder), Dr. Riccardo Levato (Utrecht).


Biomaterial Platforms in Mechanobiology

Hydrogels are important in mechanobiology as they can be engineered to replicate many of the signals found in cellular microenvironments, such as the presence of adhesion and degradation sites, controlled mechanical properties (e.g., modulus, viscoelasticity), and structure (e.g., anisotropic fibers). With this, fundamental questions related to how the microenvironment guides cellular behaviors can be investigated, especially with regards to important disease processes (e.g., fibrosis). Recent work has involved the development of engineered fibrous assemblies that mimic features of the extracellular matrix (e.g., strain-stiffening), the development of injectable viscoelastic and heterogeneous matrices that guide migration for tissue repair, and the engineering of hydrogel microwell platforms to control organoid growth and uniformity.

This work is largely related to our involvement with the National Science Foundation supported Center for Engineering MechanoBiology (CEMB) and involves collaboration with other scientists and engineers, including Dr. Robert Mauck (UPenn), Dr. Becky Wells (UPenn), Dr. Vivek Shenoy (UPenn), Dr. Guy Genin (Washington U).