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1.  Synthetic Platelets: Nanotechnology to Halt Bleeding 
Science translational medicine  2009;1(11):11ra22.
Blood loss is the major cause of death in both civilian and battlefield traumas. Methods to staunch bleeding include pressure dressings and absorbent materials. For example, Quik-clot effectively halts bleeding by absorbing large quantities of fluid and concentrating platelets to augment clotting, but these treatments are limited to compressible and exposed wounds. An ideal treatment would halt bleeding only at the injury site, be stable at room temperature, be administered easily, and work effectively for internal injuries. We have developed synthetic platelets, based on Arg-Gly-Asp functionalized nanoparticles, that halve bleeding time after intravenous administration in a rat model of major trauma. The effects of these synthetic platelets surpass other treatments including recombinant factor VIIa, which is used clinically for uncontrolled bleeding. Synthetic platelets were cleared within 24 hours at a dose of 20 mg/ml, and no complications were seen out to 7 days after infusion, the longest time point studied. These synthetic platelets may be useful for early intervention in trauma and demonstrate the role that nanotechnology can have in addressing unmet medical needs.
PMCID: PMC2992987  PMID: 20371456
PLGA; nanoparticles; PEG; hemostasis; coagulation cascade; trauma
2.  Functionalized Poly(lactic-co-glycolic acid) Enhances Drug Delivery and Provides Chemical Moieties for Surface Engineering while Preserving Biocompatibility 
Acta biomaterialia  2009;5(8):2860-2871.
Poly(lactic-co-glycolic acid) (PLGA) is one of the more widely used polymers for biomedical applications. Nonetheless, PLGA lacks chemical moieties that facilitate cellular interactions and surface chemistries. Furthermore, incorporation of hydrophilic molecules is often problematic. The integration of polymer functionalities would afford the opportunity to alter device characteristics, thereby enabling control over drug interactions, conjugations, and cellular phenomena. In an effort to introduce amine functionalities and improve polymer versatility, we synthesized two block copolymers (PLGA-PLL 502H and PLGA-PLL 503H) comprised of PLGA and Poly(ε-carbobenzoxy-L-lysine) utilizing dicyclohexyl carbodiimide (DCC) coupling. PLGA-PLL micropsheres encapsulated approximately six-fold (502H) and three-fold (503H) more vascular endothelial growth factor (VEGF), and 41% (503H) more ciliary neurotrophic factor (CNTF) than their PLGA counterparts. While the amine functionalities were amenable to the delivery of large molecules and surface conjugations, they did not comprise polymer biocompatibility. With the versatile combination of properties, biocompatibility, and ease of synthesis, these block copolymers have the potential for diverse utility in the fields of drug delivery and tissue engineering.
PMCID: PMC2749076  PMID: 19433141
Block Copolymers; PLGA; Poly(amino acid); CNTF; VEGF
3.  Engineering angiogenesis following spinal cord injury: A coculture of neural progenitor and endothelial cells in a degradable polymer implant leads to an increase in vessel density and formation of the blood-spinal cord barrier 
Angiogenesis precedes recovery following spinal cord injury (SCI), and its extent correlates with neural regeneration suggesting that angiogenesis may play a role in repair. An important precondition for studying the role of angiogenesis is the ability to induce it in a controlled manner. Previously, we showed that a coculture of endothelial cells (ECs) and neural progenitor cells (NPCs) promoted the formation of stable tubes in vitro and stable, functional vascular networks in vivo in a subcutaneous model. We sought to test whether a similar coculture would lead to formation of stable functional vessels in the spinal cord following injury. We created microvascular networks in a biodegradable two component implant system and tested the ability of the coculture or controls (lesion control, implant alone, implant plus ECs, or implant plus NPCs) to promote angiogenesis in a rat hemisection model of spinal cord injury. The coculture implant led to a four fold increase in functional vessels compared to the lesion control, implant alone, or implant plus NPCs groups and a 2 fold increase in functional vessels over the implant plus ECs group. Furthermore, half of the vessels in the coculture implant exhibited positive staining for the endothelial barrier antigen, a marker for formation of the blood spinal cord barrier (BSB). No other groups showed positive staining for the BSB in the injury epicenter. This work provides a novel method to induce angiogenesis following SCI and a foundation for studying its role in repair.
PMCID: PMC2764251  PMID: 19120441
rat; microvasculature; neural progenitor cells; endothelial cells; hydrogel; scaffold; PLGA; blood-spinal cord barrier
4.  CNTF promotes the survival and differentiation of adult spinal cord-derived oligodendrocyte precursor cells in vitro but fails to promote remyelination in vivo 
Experimental neurology  2006;204(1):485-489.
Delivery of factors capable of promoting oligodendrocyte precursor cell (OPC) survival and differentiation in vivo is an important therapeutic strategy for a variety of pathologies in which demyelination is a component, including multiple sclerosis and spinal cord injury. Ciliary neurotrophic factor (CNTF) is a neuropoietic cytokine that promotes both survival and maturation of a variety of neuronal and glial cell populations, including oligodendrocytes. Present results suggest that although CNTF has a potent survival and differentiation promoting effect in vitro on OPCs isolated from the adult spinal cord, CNTF administration in vivo is not sufficient to promote oligodendrocyte remyelination in the glial-depleted environment of unilateral ethidium bromide (EB) lesions.
PMCID: PMC2430994  PMID: 17274982
CNTF; demyelination; remyelination; oligodendrocyte precursor cell

Results 1-4 (4)