The potential utility of adult stem or progenitor cells for repair of radiation-damaged salivary glands is high, but is currently only a theoretical solution for patients suffering from xerostomia. There remain several critical obstacles that must be resolved before cell-based therapy for dysfunctional salivary glands can be moved into the clinical arena.
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Acute myeloid leukemia (AML) recurrences are attributed to leukemia stem cells (LSCs that are capable of surviving conventional chemotherapy and radiation treatments. The drug parthenolide (PTL) has shown remarkable efficacy in inducing selective apoptosis in LSCs. However, PTL's low water solubility prevents it from reaching therapeutically effective levels in the blood stream. To circumvent this problem, we are developing a novel micelle delivery system to solubilize and target PTL.
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We can interrogate and take advantage of the critical interactions between cells and extracellular matrix (ECM) to create bioactive materials capable of controlling cell function and tissue evolution (described in Figure 1). To determine the requirements of the microenvironment, we utilize hydrogels easily modified with respect to mechanical integrity, adhesive peptides, ECM molecules, degradability, and incorporation of drugs, to direct cellular differentiation through a variety of mechanisms.
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Hydrogels can be exploited to encapsulate and deliver cells and biomolecules therapeutically, as delivery characteristics can be intimately controlled through alterations in hydrogel biophysical and biochemical structure. We are interested in using hydrogels to in situ polymerize delivery systems for cells and/or therapeutics that act locally to aid ischemic tissue regeneration, wound healing, or control inflammation.
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Conventional small molecule drugs and large macromolecular drugs have significant and distinctly different delivery barriers. For example, small molecule drugs, such as the chemotherapeutic doxorubicin, is highly hydrophobic, thus administration requires toxic cosolvents to aid blood solubility. Macromolecular drugs, on the other hand, suffer from enzymatic degradation and inactivation, difficulty in targeting to the appropriate cells and transversing the cell membrane, and often become degraded intracellularly once endocytosed.
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Although most orthopaedic fractures heal, the clinical management of critical (>3mm) segmental defects continues to present major challenges for both amputation and limb salvage approaches. The periosteum plays an essential role in the healing process of both fractures and autografts. Periosteal stem cells have been shown necessary for the induction of robust endochondral and intramembraneous bone formation, essential for effective healing and neovascularization of autografts.
Learn more about Tissue Engineered Periosteum Approaches to Heal Bone Allograft Transplants