Endogenous neural stem/progenitor cells therapy is one of the most advanced clinical trial worldwide. Generally, drug is given to the targeted area through the traditional strategies such as intraventricular or intravenous delivery method. However, those methods always come with undesired side-effects such as over-dose of drug and offensive injection are not applicable to the large-scale clinical application. In this study, the clinical feasibility of blended biosynthesized cellulose duraplasty was studied. Our results showed that physical properties of BBC can be controlled through the optimized fabrication process. In addition, the time length of Middle cerebral artery occlusion rat model was tested through the 60 vs 90 mins occlusion time behavioral assessments of rat and the data indicated that 60 mins length can induce significant motor functional impairment. Finally, the EGF & EPO-loaded BBC duraplasty was implanted over the removed area and the ELISA test revealed that BBC duraplasty can release and delivery the growth factors to the targeted area (subvertical zone) at least 3 days after implantation. In summary, our BBC duraplasty is showing the potential prospection to be a clinical-applicable duraplasty to replace the traditional commercial duraplasty in the future stroke recovery therapy.

abstract: Stromal cell-derived factor-1α (SDF-1α) and its key receptor, CXCR4 are ubiquitously expressed in systems across the body (e.g. liver, skin, lung, etc.). This signaling axis regulates a myriad of physiological processes that range from maintaining of organ homeostasis in adults to, chemotaxis of stem/progenitor and immune cell types after injury. Given its potential role as a therapeutic target for diverse applications, surprisingly little is known about how SDF-1α mediated signaling propagates through native tissues. This limitation ultimately constrains rational design of interventional biomaterials that aim to target the SDF-1α/CXCR4 signaling axis. One application of particular interest is traumatic brain injury (TBI) for which, there are currently no means of targeting the underlying biochemical pathology to improve prognosis. Growing evidence suggests a relationship between SDF-1α/CXCR4 signaling and endogenous neural progenitor/stem cells (NPSC)-mediated regeneration after neural injury. Long-term modulation of the SDF-1α/CXCR4 signaling axis is thus hypothesized as a possible avenue for harnessing and amplifying endogenous regenerative mechanisms after TBI. In order to understand how the SDF-1α/CXCR4 signaling can be modulated in vivo, we first developed and characterized a sustained protein delivery platform in vitro. We were the first, to our knowledge, to demonstrate that protein release profiles from poly(D,L,-lactic-co-glycolic) acid (PLGA) particles can be tuned independent of particle fabrication parameters via centrifugal fractioning. This process of physically separating the particles altered the average diameter of a particle population, which is in turn was correlated to critical release characteristics. Secondly, we demonstrated sustained release of SDF-1α from PLGA/fibrin composites (particles embedded in fibrin) with tunable burst release as a function of fibrin concentration. Finally, we contrasted the spatiotemporal localization of endogenous SDF-1α and CXCR4 expression in response to either bolus or sustained release of exogenous SDF-1α. Sustained release of exogenous SDF-1α induced spatially diffuse endogenous SDF-1/CXCR4 expression relative to bolus SDF-1 administration; however, the observed effects were transient in both cases, persisting only to a maximum of 3 days post injection. These studies will inform future systematic evaluations of strategies that exploit SDF-1α/CXCR4 signaling for diverse applications. / Dissertation/Thesis / Doctoral Dissertation Bioengineering 2016