Department of Surgery
General Surgery Research
According to the NIH-NHLBI strategic plan, there is a great need for engineered tissues and implants to restore form and function to diseased or traumatized tissues and organs. Indeed, according to the plan; much
progress has been made in the tissue engineering/regenerative medicine field, especially in the development of first generation products, and the understanding of cell-cell and cell-matrix interactions. However, significant
knowledge gaps remain in our ability to control cell phenotype and direct tissue formation, which is the ultimate goal for both tissue engineering and regenerative medicine. Further, the use of functionalized tissue engineered constructs for in vitro assays will also play a role in drug development and toxicity screening. There are 7 basic science strategies and 9 translational strategies listed in the strategic plan. Our research is directly targeted at 6 of the basic science strategies and 5 of the translational strategies these being:
Basic Research Goals.
- Identify suitable cell sources, biomaterials, and cell-instructive strategies for specific application targets.
- Identify optimal cells for differentiation into tissues, reproducible methods for differentiating into wellcharacterized cell products, reliable scale-up procedures.
- Improve methods to control biomatrix composition, architecture, porosity, surface chemistry, degradation, strength, shape, and compliance for biomaterials.
- Develop cell-instructive approaches to limit or reverse changes in phenotypic function to improve treatment of heart failure.
- Establish new models and approaches to integrate extracellular matrix architecture, biomaterials, cellular pathways, physical, chemical, and electrical parameters for the design of biological substitutes.
- Integrate technologies into improved functional structures. An example may be improved small diameter grafts for vascular surgery.
Translational Research Goals.
- Develop functional in vitro models of human disease for testing therapies and toxicities.
- Engineer tissues from autologous cells to avoid rejection.
- Foster the development of assays, bioreactors, and automation methods.
- Improve cell culture protocols, together with reliable sources of stored cells for use in tissue engineering CV applications, to speed applications’ development.
- Develop bioreactor devices to support self-assembly of multiple cell types into complex heart tissues.
- Promote multidisciplinary partnerships and collaborations between academic investigators and industry/biotechnology to test the safety and efficacy of tissue-engineered products for CV applications in clinically relevant disease models.
- Employ human tissue-based drug screening to predict CV drug action more accurately.
The basic science and translational goals are included in several active research programs in the areas of cardiac muscle regeneration, inflammation modulation, pancreatic tissue engineering and regeneration and finally skeletal muscle regeneration. South Carolina has been the recipient of an NSF RII infrastructure grant. This grant is part of a state wide initiative to build the knowledge economy in South Carolina. Dr. Yost is the co-science director and thrust IV, biofabrication leader on for the initiative.
Skeletal Muscle Tissue Engineering.An example of the types of programs at MUSC in regenerative medicine is the skeletal muscle tissue engineering program led by Dr. Michael Yost PhD. Dr. Yost has a PhD in chemical engineering and is an associate professor of Surgery. Muscle loss due to trauma, tumor resection or congenital malformation is devastating to the patient and their family. The loss of the ability to close one’s eyes, chew food or smile at a loved one leaves deep physical and emotional scars on the patient. Most current therapies involve creative rearrangement of skin and muscle flaps to mitigate the deformity. Since these procedures transpose tissues from other locations, the results are often sub-optimal. A percentage of mobilized flap tissues contract, atrophy and/or die and do not function like the original tissue. Skeletal muscle is one of the few tissues in the human body that has significant regenerative capacity. This capacity is due to the presence of satellite cells. These cells become activated and participate in the repair of damaged skeletal muscle. Unfortunately, large defects such as those created by some major surgical procedures cannot be healed regeneratively via endogenous satellite cells. Our research addresses the problem of muscle regeneration by combining modulation of inflammatory processes with tissue engineering-based regeneration strategies. The overall goal is to seamlessly regenerate fascicular segments of skeletal muscle.
Advanced Tissue Biofabrication Laboratory. As part of our collaboration with Regenerative medicine, trainees will have full and complete access to the Advanced Tissue Biofabrication laboratory located at MUSC. The facility has many multipurpose Biofabrication tools to facilitate research in regenerative medicine and tissue engineering. The long term goals for the ATBC are to serve as a hub for building and enhancing tissue biofabrication technologies that will: (1) develop into a statewide center of excellence at the interface of engineering, biomathematics and developmental biology; (2) create a transdisciplinary culture of innovation in tissue science and engineering research that links scientific discovery to innovation in advanced bioprinting (tissue biofabrication) technology; (3) produce a diverse group of graduates and trainees who will be creative innovators in an emerging, new biofabrication industry; (4) attract broad interest by faculty and students at colleges and universities across the state; and (5) serve to guide, focus and transform the enhancement of infrastructure into a large scale vision capable of stimulating competitive research proposals and sustainable partnerships among academe and the private sector. One of our surgical research resident will be working on this project starting the summer of 2013. Some of the key equipment available to trainees in the facility is highlighted below: Spheroid Positioner & Cell/Gel Sprayer, Eppendorf epMotion 5070, DynaGen Bioreactor System, Bose ElectroForce 3100 Test Instrument with WinTest Controls, INSTRON 5942 Low-Force Universal Testing System, NIKON TE-2000S Inverted Microscope with Photometrics HQ2 Camera & DV2, Ion PGM™ Sequencer, and the Palmetto Printer, a fully automated bioprinter developed by MUSC and Clemson researchers at the ATBC, and assembled by Izumi International of Greenville, SC. The printing head is designed with the ability to Fishman Dispensors for positioning multicellular spheroids. To build 3D tissues, biocompatible materials, such as hydrogels, and/or extracellular matrices with or without cells, can be sprayed onto the patterned spheroids through aerosol dispensers. These are some of the unique resources available to advance translational science for the bioengineering trainee.