- 3D Printing in Biomedical Research
- Tissue Engineering and Regenerative Medicine
- Cellular Mechanics and Interactions
- Cancer Cells and Metastasis
- Hydrogels: synthesis, properties, applications
- Proteoglycans and glycosaminoglycans research
- Mesenchymal stem cell research
- Neonatal Respiratory Health Research
- Osteoarthritis Treatment and Mechanisms
- Muscle Physiology and Disorders
- Inhalation and Respiratory Drug Delivery
- RNA Interference and Gene Delivery
- Hippo pathway signaling and YAP/TAZ
- Cell Adhesion Molecules Research
- Advanced Materials and Mechanics
- Congenital gastrointestinal and neural anomalies
- Cancer Genomics and Diagnostics
- Digestive system and related health
- Angiogenesis and VEGF in Cancer
- Cancer Research and Treatments
- Bone Metabolism and Diseases
- Extracellular vesicles in disease
- Esophageal Cancer Research and Treatment
- Energy Harvesting in Wireless Networks
- Orthopaedic implants and arthroplasty
University of Michigan–Ann Arbor
2022-2025
University of Pennsylvania
2017-2024
Philadelphia VA Medical Center
2020-2021
Philadelphia University
2019
California University of Pennsylvania
2019
AO Foundation
2014-2017
ETH Zurich
2014-2017
Abstract 3D culture of cells in designer biomaterial matrices provides a biomimetic cellular microenvironment and can yield critical insights into behaviours not available from conventional 2D cultures. Hydrogels with dynamic properties, achieved by incorporating either degradable structural components or reversible crosslinks, enable efficient cell adaptation the matrix support associated functions. Herein we demonstrate that given similar equilibrium binding constants, hydrogels containing...
Transitioning lung for postnatal life The is a complex organ composed of multiple cell types, and its alveolus serves as the functional unit gas exchange. alveolar type 1 (AT1) an active signaling hub in developing mouse human lung. Zepp et al. generated comprehensive single-cell atlas murine identified differentiation cell-to-cell communication transitions to air breathing. AT1 cells spatially aligned with stromal progenitors formed that preferentially communicated transient,...
Multiple myeloma (MM), a hematologic malignancy that preferentially colonizes the bone marrow, remains incurable with survival rate of 3 to 6 mo for those advanced disease despite great efforts develop effective therapies. Thus, there is an urgent clinical need innovative and more MM therapeutics. Insights suggest endothelial cells within marrow microenvironment play critical role. Specifically, cyclophilin A (CyPA), homing factor secreted by (BMECs), homing, progression, survival,...
Folding of mucosal tissues, such as the tissue within epithelium upper respiratory airways, is critical for organ function. Studying influence folded patterns on cellular function challenging mainly due to lack suitable cell culture platforms that can recreate dynamic folding in vitro. Here, a bilayer hydrogel system, composed alginate/polyacrylamide double-network (DN) and hyaluronic acid (HA) hydrogels, generate static based mechanical instabilities, described. By encapsulating human...
Human intestinal organoids (HIOs) derived from human pluripotent stem cells co-differentiate both epithelial and mesenchymal lineages in vitro but lack important cell types such as neurons, endothelial cells, smooth muscle, which limits translational potential. Here, we demonstrate that the niche factor, EPIREGULIN (EREG), enhances HIO differentiation with epithelium, mesenchyme, enteric neuroglial populations, organized muscle a single differentiation, without need for co-culture. When...
Runx2 is one of the most studied transcription factors expressed in mesenchymal stem cells (MSCs) upon their commitment toward an osteogenic differentiation. During endochondral bone formation vivo, Sox9 directly interacts with and represses its activity; however, role direct osteogenesis vitro has been largely overlooked.Bone marrow-derived human MSCs (hMSCs) were cultured either control or medium supplemented dexamethasone (DEX). To further investigate vitro, hMSCs treated siRNA.We show...
Hydrogels are engineered with biochemical and biophysical signals to recreate aspects of the native microenvironment control cellular functions such as differentiation matrix deposition. This deposited accumulates within pericellular space likely affects interactions between encapsulated cells hydrogel; however, there has been little work study spatiotemporal evolution at this interface. To address this, metabolic labeling is employed visualize temporal spatial positioning nascent proteins...
Epithelial cell organoids have increased opportunities to probe questions on tissue development and disease in vitro for therapeutic transplantation. Despite their potential, current protocols grow these almost exclusively depend culture within 3D Matrigel, which limits defined conditions, introduces animal components, results heterogenous (i.e., shape, size, composition). Here, a method is described that relies hyaluronic acid hydrogels the generation expansion of lung alveolar...
Given the significance of hydrogels as cell-instructive materials, it is important to understand how differences in their chemical and physical properties are able direct cell fate. For example, remains unclear different hydrogel cross-linking chemistries gelation mechanisms influence behavior. Here, we report on hyaluronan-tyramine (HA-Tyr) prepared either with enzymatic using horseradish peroxidase H2O2 or visible light (500 nm) triggered gelation. We demonstrate that when polymerized...
Photo-cross-linking of tyramine-substituted hyaluronan (HA-Tyr) hydrogels is demonstrated for the first time. HA-Tyr are fabricated via a rapid photosensitized process using visible light illumination. Nontoxic conditions offer photoencapsulation human mesenchymal stromal cells (hMSCs) with high viability. Macroscopic gels can be formed in less than 10 s, and one- two-photon photopatterning enable 2D 3D microfabrication. Different degrees cross-linking induce different swelling/shrinking,...
Supramolecular chemistry has enabled the design of tunable biomaterials that mimic dynamic and viscoelastic characteristics extracellular matrix.
Abstract Cartilage injuries and subsequent tissue deterioration impact millions of patients. Since the regeneration functional hyaline cartilage remains elusive, methods to stabilize remaining tissue, prevent further deterioration, would be significant clinical utility prolong joint function. Finite element modeling shows that fortification degenerate (Reinforcement) reestablishment a superficial zone (Sealing) are both required restore fluid pressurization within restrict flow matrix loss...
Epithelial organoids derived from intestinal tissue, called enteroids, recapitulate many aspects of the organ in vitro and can be used for biological discovery, personalized medicine, drug development. Here, we interrogated cell signaling environment within developing human intestine to identify niche cues that may important epithelial development homeostasis. We identified an EGF family member, EPIREGULIN (EREG), which is robustly expressed crypt. Enteroids generated grown standard culture...
Increased extracellular matrix (ECM) stiffness has been implicated in esophageal adenocarcinoma (EAC) progression, metastasis, and resistance to therapy. However, the underlying pro-tumorigenic pathways are yet be defined. Additional work is needed develop physiologically relevant vitro 3D culture models that better recapitulate human tumor microenvironment can used dissect contributions of EAC pathogenesis. Here, we describe a modular, ECM-mimetic hydrogel platform with tunable mechanical...