Tissue Engineering-Based Rehabilitation
The goal of rehabilitation is the restoration of form and function. This often requires permanent implants as replacements for tissues and organs or external devices to augment function. Tissue engineering (also referred to as "regenerative medicine") offers a new way of achieving the goals of rehabilitation through the regeneration of tissues and organs. Our multidisciplinary, international team is employing advanced methodologies in materials science and engineering, mechanical engineering, and cell and molecular biology. Nanotechnology is being used in the fabrication of nanoparticles as gene delivery vehicles in conjunction with our tissue engineering scaffolds.
Specific Objective
The specific objective is to facilitate tissue regeneration through the implantation of a collagen sponge-like scaffold alone, seeded with cells, or incorporating genes.
Clinical Endpoints
While the overall goal is full regeneration of the tissue or organ, improvement in the reparative process with partial regeneration of the tissue may yield a meaningful clinical outcome.
THE TOOLS THAT WE EMPLOY FOR TISSUE ENGINEERING/REGENERATIVE MEDICINE
• SCAFFOLD (MATRIX)
– Porous, absorbable natural biomaterial (collagen-GAG copolymers)
• CELLS (Autologous)
– Differentiated cells
– Mesenchymal stem cells
• REGULATORS
– Genes for selected growth factors
– Culture environments: Static and dynamic
OUR APPROACH
• Identify the clinical problem involving the loss of tissue as a result of trauma or disease.
• Identify/develop animal models.
• Investigate the interactions of the cells from the tissue with candidate collagen scaffolds in vitro.
• Implant the scaffold into the animal model alone, seeded with differentiated or stem cells, or incorporating genes.
RESEARCH AND DEVELOPMENT FOCUS
Scaffolds
The tissue engineering triad includes scaffolds (also referred to as matrices), cells, and soluble regulators (e.g., growth factors). Biomaterials employed for the fabrication of scaffolds play a critical role in tissue engineering/regenerative medicine. Scaffolds for engineering bone and the soft tissues have included synthetic and natural calcium phosphates and myriad synthetic (e.g., polylactic acid and polyglycolic acid ) and natural (e.g., collagen and fibrin) polymers. Scaffolds, for engineering tissue in vitro or to be used as implants to facilitate regeneration in vivo, need to have a microstructure and chemical composition necessary to accommodate parenchymal and stromal cells and their functions. In this regard a porous structure is generally necessary. The required porosity and pore diameter, pore distribution, and pore orientation, might be expected to vary with tissue type. The chemical composition of the matrix is important with respect to its influence on cell adhesion and the phenotypic expression of the infiltrating cells. Moreover, because the objective is the regeneration of the original tissue, the scaffold needs to be absorbable. The degradation rate of the material generally may be determined based on the rate of new tissue formation and the normal period for remodeling of the tissue at the site of implantation. Of course, it is important to consider the effects of moieties released during degradation of the matrix on the host and regenerating tissue. Finally, the mechanical properties of the biomaterial employed as a scaffold for tissue engineering are important for providing temporary support of applied loading in vivo during the regeneration process and for resisting the contractile forces that may be exerted by the seeded cells prior to implantation and by cells infiltrating the scaffold in vivo.
A matrix can play several roles during the process of regeneration in vivo. It can: structurally reinforce the defect site, serve as a barrier to the ingress of surrounding tissue, serve as a scaffold for migration and proliferation of cells in vivo or for cells seeded in vitro, serve as an insoluble regulator of cell function through its interaction with integrins and cell receptors, and serve as a delivery vehicle for cells, growth factors, and genes.
Our design approach has been to employ materials that can serve as analogs of the extracellular matrix of the tissue to be engineered. This concept recognizes that the molecular composition and architecture of the extracellular matrix displays chemical and mechanical properties required by the parenchymal cells and the physiological demands of the tissue. To this end we use collagen-glycosaminoglycan copolymers for the fabrication of scaffolds for soft tissue engineering, and natural bone mineral for bone applications.
Cells
One of the novel approaches being employed in our studies is the use of bone marrow-derived mesenchymal stem cells for seeding our scaffolds for the regeneration of musculoskeletal tissues. In some cases the cells may be induced to differentiate into specific cell types in vitro prior to implantation, and in other cases that differentiation may best take place in vivo under the control of local endogenous cues.
Regulators
In some cases, the genetic modification of cells participating in tissue engineering may accelerate the process. These considerations provide compelling rationale for the new approaches of wedding gene transfer with tissue engineering strategies. To this end we have begun to incorporate genes into the collagen-glycosaminoglycan scaffold. We have found that this system is an effective means for non-viral gene transfer.
Our Technology Learn more about the basic science that underscores our Research and Development and product history. more [...] |
Research Papers Learn more about some our publications. more [...] |
Other Resources Federal Grant Support information.
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