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Traumatic brain injury (TBI) leads to a cascade of primary and secondary neurodegenerative events, often causing lifelong disabilities. Brain-derived neurotrophic factor (BDNF) is a potential therapeutic for functional recovery of neurons. Unfortunately, BDNF is unstable and expensive, making direct infusion impractical. Therefore, we sought to develop a controlled release formulation to deliver BDNF. Our therapeutic construct encapsulates BDNF in poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs), and further encapsulates these NPs in an alginate hydrogel. Encapsulating BDNF within NPs protects and assists in drug delivery, while further encapsulating the BDNF-NPs in alginate enables localization and sustained release. The BDNF-NPs were synthesized and evaluated for size, stability and BDNF release profile. A MATLAB model was developed to determine the approximate quantity of BDNF-NPs needed to evaluate therapeutic efficacy in neurons injured with hydrogen peroxide. We then compared the therapeutic efficacy and BDNF release profile of these BDNF-NPs to our novel alginate/BDNF-NP formulation. We have successfully designed and fabricated a double encapsulation positionally controllable construct that preserves BDNF bioactivity and extends its release. We also demonstrated that very low dosages of BDNF may be equally effective in promoting neuroprotection, thereby potentially reducing therapeutic costs without compromising efficacy. Our novel formulation offers a promising avenue for treating severe TBI and other neurological disorders which would benefit from a long-lasting and positionally controllable neuroprotective treatment. This approach can easily accommodate additional biologics for localized drug delivery with minimal re-formulation.

This research investigates the performance of an assembly micro-atomizer under single-fluid and twin-fluid operational conditions of micro-encapsulation process. Alginate and CaCl₂ aqueous solution are used as the membrane material and hardening agent, respectively. The high speed images were taken to investigate the formation processes of the microcapsules. Results showed that the formation of the microcapsules depends on the instability modes of the liquid column including asymmetry mode, helical mode, sinusoidal mode and spray developing mode as Reynolds number was increased from 221 to 2210. Excitation at resonance frequency of 2.18 kHz of this system resulted in the production of uniform-sized microcapsules. Moreover, SMD equal to 20 μm can be achieved in low GLR under twin-fluid atomization process. It is not easy to achieve by commercial apparatus.

This research investigates the micro-encapsulation process with a pressure-type micro-atomizer. Alginate and CaCl₂ aqueous solution are used as the membrane material and hardening agent, respectively. The high speed images were taken to investigate the formation processes of the microcapsules. Results show that the geometric shape of the microcapsules was sensitive to the droplet flying distant and the concentration of alginate aqueous, however, insensitive to the concentration of CaCl₂ aqueous. Results also show that the membrane thickness of the microcapsules was controlled by the diffusion processes of calcium chloride. An empirical formula was derived to describe the rate change of the membrane thickness in the hardening processes.

The loss or failure of an organ or tissue is one of the most frequent, devastating, and costly problems in human healthcare. The areas of regenerative medicine and tissue engineering apply the principles of chemistry, biology, and engineering to create new tissues and organs. Here we discuss some of the early work in this field and, in particular, review our studies combining chemistry, materials science, biology, and engineering to create new tissues and organs.