For the in vivo approach to tissue or organ replacement, we are interested in developing scaffolds and techniques that will be conducive to the reconstitution or maintenance of normal tissue micro architecture. Disruption of normal tissue microarchitecture can lead to scarring or degeneration resulting in loss of or impaired function. Therefore, we are developing and studying novel biomaterials and processing techniques to produce scaffolds suitable for tissue engineering. In particular we are interested in understanding the effects of scaffold characteristics on cellular and tissue development in order to prevent deleterious processes. Moreover, we have developed an approach to harvest patient-specific endothelial progenitor cells and are investigating methods for cell-specific differentiation.
By using the basic chemistry of ester bonds, novel functional materials have been synthesized based on citric acid, a tri-functional natural monomer, and aliphatic diols of different length. These polyesters, referred to as polydiolcitrates, may display elastomeric or thermoresponsive properties and exhibit intrinsic antioxidant properties. They allow for further functionalization and customizable mechanical properties and degradation times.
Some of the approaches currently under study are:
Hydrogels(in collaboration with the Szleifer lab)
Serum albumin is the most abundant plasma protein found in the human body and it has been used extensively in medical applications for coating surfaces and improving biological performance . It is well known that gelation of these plasma proteins is possible with high temperature treatments or the addition of crosslinking agents such as glutaraldehyde. However, we have developed a method which forms albumin gels without employing the use of crosslinkers and maintaining fabrication temperatures at or below physiological conditions (37C). Acidic conditions alter the structure of the albumin protein from its native state towards fast and extended conformations. In these conformations and at high concentrations, intermolecular forces draw proteins together into bundles which are irreversibly bound in physiological environments. Investigation of this gelation mechanism is pursued from both an experimental (Ameer Lab) and theoretical perspective (Szleifer Lab). Impregnation of these gels with small caliber (<6mm) grafts may improve their patency due to good biological performance of albumin gels.
Drug and Gene DeliveryPolymeric scaffolds loaded with constructs have been proposed for substrate-mediated gene delivery to control the location and duration of gene expression. We are investigating the utility of a biodegradable and biocompatible, citric acid-based polymeric scaffold as a substrate for gene delivery. Polydiolcitrate scaffolds (PDC, with POC being one example) offer great flexibility for modifying the degradation rate, pore size, and degree of porosity to influence gene loading capacity and cellular infiltration, thereby affecting transfection efficiencies. Furthermore, because PDC can be modified to mimic native tissues such as bone, cartilage, and vascular tissue, it holds great promise for gene therapy in a variety of applications.
(Sherry Zhu, Komal Prem)
Stem cell differentiation(in collaboration with the Mrksich lab)
Induced pluripotent stem (iPS) cells have the ability to differentiate into any cell type in the body, which makes them an ideal source for a variety of cell-based tissue engineering applications. One major safety concern, however, is the tendency of iPS cells to spontaneously form teratomas – a certain type of tumors - upon implantation. Therefore, complete differentiation of these cells has to be carried out in vitro under controlled conditions in order to produce a high yield of terminally differentiated cells prior to implantation.
We hypothesize that precise control over surface chemistry can be used to enhance directed iPS cell differentiation, and potentially minimize the immunogenicity of the resulting cells. To evaluate this hypothesis, we are studying the effects of controlled surface presentation of the RGD adhesion ligand on iPS cell differentiation and immunogenicity.
Successful completion of these studies would allow us to design stem-cell niche directed therapies aimed at maximizing the yield of lineage-specific cells while maintaining low immunogenicity. The long-term goal of this project is to direct the differentiation of iPS cells in order to produce functional autologous vascular cells for cell-based tissue-engineering therapies. Accomplishing this goal will contribute toward establishing vascular cell sources that can be used to improve current treatments of cardiovascular disease. (Bin Jiang)
Tissue engineeringTissue engineering is a relatively new field that integrates material science, polymer chemistry, and cell/molecular biology in order to better understand, repair or regenerate tissues and organ systems. In this area, we are currently pursuing two main avenues:
Vascular tissue engineering:
disease is the number one killer in the U.S.A. and vascular disease is
a significant contributor to the number of deaths. We are interested in
designing and evaluating biodegradable materials that would be
conducive to the formation of small-diameter blood vessels.An ideal
engineered vascular graft should be non-thrombogenic, non-toxic, and
have viscoelastic properties that are similar to those of the native
host vessel it will replace. Several laboratories have been
investigating various scaffold materials and cell sources in an attempt
to meet these requirements. Many of the approaches require the creation
of a functional endothelial cell monolayer within the lumen of the
graft. This requirement has prompted significant research into the use
of adult stem cells differentiated into endothelial-like cells to cover
the scaffold. One potential source of adult stem cells is endothelial
progenitor cells (EPCs) found in circulating peripheral blood. There
are few studies on the interactions of these cells with biomaterials
for potential applications in vascular tissue engineering,
specifically, the engineering of a functional endothelium. Our lab is
interested in a) the characterization and use of progenitor cells from
blood for tissue generation, and b) the effect of the mechanical
properties of the biomaterial scaffold on cell signaling and tissue
generation. Also, we have a special interest in understanding the
scaffold parameters that would modulate and enable functional tissue
engineering in vivo.
Orthopaedic tissue engineering:
Orthopaedic research is an exciting field that is also in high demand due to the growing elderly population as well as the rise in sports-related injuries. We are specifically addressing problems associated with bone defects and injuries to the ligaments. The addition of hydroxyapatite (HA) and other bioceramics to our poly(octanediol-co-citrate) (POC) polymer forms a composite (POC-HA) that suits the mechanical and degradation properties for bone and ligament tissue engineering. For our bone defect project, our goal is to create a material that is osteoconductive and osteoinductive and that which can initially restore a bone defect, but eventually be replaced by the host's tissue over time. Using material science, molecular biology, and clinical prinicipals, mesenchymal stem cells are used as the cell source to engineer biomaterial- and cell-based bone graft.
our ligament project, our
efforts on engineering a
ligament are focused
on the development of a composite scaffold that would support cyclic
loading and cell infiltration
in the intra-articular component of the scaffold while promoting bone
growth at the fixation
points. Specifically, the concept
behind the patellar tendon graft will be used to fabricate a ligament replacement to be ultimately
tested in rabbit knes. Sandwiched between two "bony-ends" of POC-HA,
biodegradable fibers act as the ligament portion of the entire