Research
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This research area includes several of the other research areas/projects.
Our lab will work in conjunction with our collaborators in order to produce new biomaterials in many different forms from nano fibers to hydrogels for a variety of tissue engineering purposes.
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Research Team
Current:
Brittany Taylor
Project Alumni:
Tea Andric, Eemahni Cooper,
Katherine Degen, & Alana Sampson
Bone is a connective tissue that is a composite by nature with an intricate hierarchical structure. Current methods for bone replacement include autografts, allografts, and metallic replacements. Our lab is developing a new tissue-engineered approach to bone replacement, repair, and regeneration using degradable, composite nano and microstructures.
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The specific research area described below is not currently under investigation, but another closely-related project currently aims to research and develop healing strategies for tendons and ligaments (i.e., due to connective tissue disorders).
Research Team
Current:
Emmanuel EkwuemeProject Alumni:
Yvonne Empson, Danielle Paynter, & Gabrielle Stiff
Cartilage is a form of extracellular matrix secreted by specialized cells called chondrocytes. Articular cartilage serves as a shock absorber and is essentially frictionless, providing a smooth surface for the contact and movement of the bones in joints.
Osteoarthritis (OA) is the most prevalent musculoskeletal disease in humans characterized by degeneration and loss of articular cartilage. Genetic factors, age related wear and tear processes, and acute trauma contribute to cartilage degradation and OA. Biomechanical forces increase inflammatory mediator production by chondrocytes and potentiates abnormal cartilage function in the degenerative joint.
Normal articular cartilage consists of four zones (superficial or tangential, intermediate or transitional, deep or radical, and calcified) and differs in their collage fibril orientation. The superficial zone (~200 um) contains primarily thin type II collagen fibrils and tend to run primarily parallel to the plane of the articular surface with some degree of parallel orientation in that plane.
Due to the nature and function of the articular joint, biomechanical forces, integrity and orientation of collagen play a crucial role in determining chondrocyte behavior. In our laboratory we look to investigate the roles of collagen fiber integrity and orientation on chondrocyte behavior and the progression of OA.
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Research Team
Current:
Albert Kwansa
Project Alumni:
Donnie Damon Jr., Anneke Nelson,
Alana Sampson, & Valerie Walters
Type I Collagen
Collagens are major structural proteins in vertebrates that store and transmit energy in the musculoskeleton. Collagens are present in most of the connective and supportive tissues in vertebrates, and they make up almost 30% of all protein in the human body and 90% of the organic material in bone. Approximately, 20 types of collagens have been identified; bones, skin, tendons, and ligaments contain mainly type I collagen; therefore, the type I collagen molecule plays an important role in energy storage in connective tissues.
The type I collagen molecule is a triple helix composed of three polypeptide chains, each exhibiting a left-handed helix. Together, these three chains form a right-handed triple helix. In collagen type I, two of these chains (termed alpha 1) have the same amino acid sequence, while the third chain (termed alpha 2) has a slightly different combination of amino acids. The triple helix is approximately 300 nm long and 1.5 nm wide with about 1000 amino acids per chain. These chains contain a glycine (Gly)-X-Y repeating pattern, where X and Y are commonly Proline (Pro) and Hydroxyproline (Hyp), respectively; however, the X and Y positions can be occupied by a number of other amino acids.
A section of a collagen molecule composed of three amino acid chains (green, red, yellow) assembled into a triple helix.
Collagens as Biomaterials
Type I collagen can self-assemble into structures called fibrils (tens to hundreds of nm in diameter) with a quarter-staggered packing array of molecules. This quarter-stagger produces a characteristic banding pattern that can be seen with electron microscopy.For the experimental aspect of this project, we are seeking to study collagen type I as a biomaterial for potential tissue engineering applications. We are employing the self-assembling nature of collagen type I to reconstitute the molecules into biomaterials such as fibers and films/membranes.
Molecular Modeling
The molecular modeling approach that we are currently using is called molecular mechanics, which is based on principles from classical physics. In this modeling approach, atoms are represented by hard spheres.
Covalent bonds are represented by spring-like connections that store potential energy whenever deviated from equilibrium (i.e., the energy stored when a spring is stretched or compressed).
Non-covalent bonds are often modeled by Lennard-Jones and Coulombic terms. The Coulombic term represents the attraction and repulsion between atoms due to their partial charges (i.e., opposite charges repel and like charges attract). The strength of this attraction/repulsion is based on the magnitude of the charges and the distance between the atoms. The Lennard-Jones term includes attractions due to van der Waals interactions and repulsions that occur when two non-bonded atoms come too close together (i.e., the hard spheres, representing the atoms, cannot overlap with each other).
With this modeling approach, the total potential energy stored in a molecule is described by a summation of various energy terms that often consider the stretching of bonds, the bending of bond angles, the twisting about bonds, out-of-plane bending around a central atom, and non-bonded interactions (Lennard-Jones and Coulombic).
We are interested in modeling and predicting the mechanical behavior of type I collagen to better understand the mechanical resiliency of this protein (i.e., how this protein stores elastic energy). This mechanical resiliency is important in the transmission of forces within collagen and in collagenous tissues such as tendons and ligaments.
A section of the d band of type I collagen (top), the entire d band (middle), and the d band strained 5% (bottom). Each section has with 3 repeats of Gly-Pro-Hyp on the ends of each chain. This image was generated using SYBYL as part of a molecular model of type I collagen.
The following lists some of the resources that we have found helpful for the molecular modeling aspect of our work:
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Research Team
Current:
Kristin McKeon Fischer
Project Alumni:
Dan Flagg & Abasha Lewis
Muscle contraction can be interrupted by traumatic injuries to peripheral nerves (PNs) and/or skeletal muscle. After a muscle is injured, necrotic muscle fibers are removed and satellite cells are activated to help regenerate the skeletal muscle. However, this process results in scar tissue formation and loss of muscle function. Autologous muscle transplants and exogenous myogenic cells, satellite cells, and myoblasts have also been investigated with little success. Loss of skeletal muscle has no satisfactory restoration method currently. We are developing a new electrospun biodegradable, biocompatible, and conductive scaffolding for muscle tissue engineering
An electrospun polymer scaffold for muscle cells.
Muscle cells grown on an electrospun scaffold and stained with fluorescent dyes for actin filaments (green) and nuclei (blue). -
Research Team
Current:
Cara Buchanan & Chris Szot
In vitro tumor models are invaluable systems for studying the dynamic and progressive behavior of cancer under controlled conditions. They minimize outside interactions that often complicate in vivo models and allow for targeting the specific response of a treatment. Current in vitro studies of tumorigenesis are limited by the use of static, two-dimensional (2D) cell culture monolayers that lack the structural architecture necessary for cell-cell interaction and mass transport. These conventional systems also poorly reflect cell signaling pathways and the role of tumor microenvironment on cancer growth. With recent advances in tissue engineering, the formation of three-dimensional (3D) cellular co-cultures that are morphologically and functionally differentiated have been utilized for investigation of cancer cell signaling pathways and tumorigenesis. While these systems have helped provide significant insights into cancer biology, there remains a limited understanding of the mechanisms that govern tumorigenesis.
Our lab is currently developing in vitro tumor models to help elucidate the mechanisms of tumorigenesis in a controlled environment. Using tissue engineering techniques, novel biomaterial scaffolds and bioreactors are being utilized to co-culture multiple cell types including cancer cells, endothelial, epithelial and other stromal cells to create an organotypic culture system. Of particular interest are the mechanisms of mammary carcinogenesis, such as the effect of extracellular matrix stiffness on the progression of ductal carcinoma, as well diffusion of angiogenic cues to modulate an aggressive cancer phenotype.