Full thickness rotator cuff tears (RCT) and the associated muscle degeneration that results due to this injury presents a significant clinical burden. The prevention or recovery from this degeneration requires the synchronized behavior of many cells that participate in regeneration. Strategies that tune the inflammatory cascade that is initiated after injury serves as a powerful way to influence tissue repair. Here, we use the local, sustained delivery of the immunomodulatory small molecule FTY720 to examine whether the recruitment of pro-regenerative myeloid cells affects the healing outcome. We find that PLGA microparticles have an atrophic effect on the muscle that is ameliorated with the release of FTY720. However, the inability of FTY720 delivery to induce pro-regenerative monocyte and macrophage recruitment and our findings demonstrating enrichment of CD4+ T cells suggest that effects of this small molecule are context dependent and that the underlying mechanisms behind this RCT associated muscle degeneration require further studies.

Tumor tissue has different acidity compared to normal tissue. Localized drug delivery that release chemotherapeutic medications upon stimulation via pH changes is a promising strategy in cancer therapy for adjuvant therapies after surgical resection to reduce the risk of local recurrence. In this study, a mesoporous nanofibrous system with acidic pH-triggered “caps” has been for the first time developed for localized on-demand drug release to target tumor cells, without biological damage to normal cells while maintaining their structural integrity to support future tissue regeneration. Specifically, polyacrylic acid (PAA) was grafted on electrospun mesoporous silica nanofibers (MSFs) and the obtained PAA-MSFs allowed efficient drug loading at neural pH and on-demand releasing at acidic cancer subcellular compartments, based on pH-dependent electrostatic interactions associated with protonation/deprotonation of PAA. The The hybrid mesoporous nanofibers a low cytotoxicity to normal cells and a high killing efficiency to cancer cells. The system demonstrated a great potential as tumor targeting drug delivery system.

One of the goals of soft robotics is the ability to interface with the human body. Traditionally, silicone materials have dominated the field of soft robotics. In order to shift to materials that are more compatible with the body, developments will have to be made into biodegradable and biocompatible soft robots. This investigation focused on developing gummy actuators which are biodegradable, edible, and tasty. Creating biodegradable and edible actuators can be both sold as an interactive candy product and also inform the design of implantable soft robotic devices. First, commercially available gelatin-based candies were recast into pneumatic actuators utilizing molds. Edible robotic devices were pneumatically actuated repeatedly (up to n=8 actuations) using a 150 psi power inflator. To improve upon the properties of actuators formed from commercially available candy, a novel gelatin-based formulation, termed the “Fordmula” was also developed and used to create functional actuators. To investigate the mechanics and functionality of the recast gummy material and the Fordmula, compression testing and biodegradation studies were performed. Mechanical compression tests showed that recast gummy materials had similar properties to commercially available candies and at low strain had similar behavior to traditional silicone materials. Degradation studies showed that actuation was possible within 15 minutes in a biologically relevant solution followed by complete dissolution of the actuator afterwards. A taste test with elementary aged children demonstrated the fun, edible, and educational appeal of the candy actuators. Edible actuator development was an entry and winning submission in the High School Division of the Soft Robotics Toolkit Design Competition hosted by Harvard University. Demonstration of edible soft robotic actuators created by middle and high school aged students shows the applicability of the Soft Robotics Toolkit for K12 STEM education.

Silver nanoparticle based microelectrodes embedded between layers of hydrogel material were successfully fabricated. 3D bioprinting is employed to print the entire bioelectronics platform comprising of conducting silver ink and Gelatin methacryloyl (GelMA) hydrogel. The additive manufacturing technique of bioprinting gives design freedom for the circuit, saves material and shortens the time to fabricate the bioelectronics platform. The silver platform shows excellent electrical conductivity, structural flexibility and stability in wet environment. It is tested for biocompatibility using C2C12 murine myoblasts cell line. The work demonstrates the potential of the fabricated platform for the realization of practical bioelectronic devices.

Bacterial cultures exposed to iron-doped apatite nanoparticles (IDANPs) prior to the introduction of antagonistic viruses experience up to 2.3 times the bacterial destruction observed in control cultures. Maximum antibacterial activity of these bacteria-specific viruses, or phage, occurs after bacterial cultures have been exposed to IDANPs for 1 hr prior to phage introduction, demonstrating that IDANP-assisted phage therapy would not be straight forward, but would instead require controlled time release of IDANPs and phage. These findings motivated the design of an electrospun nanofiber mesh treatment delivery system that allows burst release of IDANPs, followed by slow, consistent release of phage for treatment of topical bacterial infections. IDANPs resemble hydroxyapatite, a biocompatible mineral analogous to the inorganic constituent of mammalian bone, which has been approved by the Food and Drug Administration for many biomedical purposes. The composite nanofiber mesh was designed for IDANP-assisted phage therapy treatment of topical wounds and consists of a superficial, rapid release layer of polyethylene oxide (PEO) fibers doped with IDANPs, followed by inner, coaxial polycaprolactone / polyethylene glycol (PCL/PEG) blended polymer fiber layer for slower phage delivery. Our investigations have established that IDANP-doped PEO fibers are effective vehicles for dissemination of IDANPs for bacterial exposure and resultant increased bacterial death by phage. In this work, slower delivery of the phage behind IDANPs was accomplished using coaxial, electrospun fibers composed of PCL/PEG polymer blend.

Novel methods are needed to traverse the blood-brain barrier and deliver drugs to specific targets in the brain. To this end, MS2 bacteriophage was explored as a multifunctional transport and targeting vector. The MS2 capsid exterior was modified with two different targeting moieties for delivery across the BBB and targeting specific regions of interest in the brain. Successful modification of MS2 capsids with a brain targeting peptide and NMADAR2D-targeting antibody was confirmed by immunoblotting and fluorescence detection. To measure transport efficiency of MS2 particles across an in vitro BBB model, a highly sensitive RT-qPCR protocol was developed and implemented. Finally, in order to demonstrate the potential of MS2 as a drug delivery vehicle, nucleotide-mediated loading of capsids was investigated with the MRI contrast agent Gd-DOTA modified with psoralen.

Polycationic particles based on a degradable oligoester core are interesting candidate materials for the transfection of polyanionic macromolecules like DNA, which would enable the degradation after delivery of condensed molecules. Good transfection efficiencies can be obtained when the size of the polyplex (containing both polycationic nanoparticles and polyanionic macromolecules) does not exceed 120 nm. Therefore, here we explored how size, but also dispersity, and surface charge of these carrier systems can be adjusted by variation of the block copolymer composition or the presence and ratio of a co-assembly agent. Polycationic particles were obtained based on an amphiphilic triblock copolymer from oligo[(ε-caprolactone)-co-glycolide] (CG) functionalized with polyethyleneimine (PEI) and diblock copolymer based on poly(ethylene glycol) (PEG) modified with CG. A second series of particles was created, in which the oligoester blocks contained only ε-caprolactone units, therefore the effect of the presence of glycolide units was also studied. In both series, the ratio between di- and triblock copolymers was systematically varied. Nano-sized particles ranging from 34.5 ± 0.2 nm to 97.9 ± 0.3 nm with controllable positive surface charges between 2.9 ± 0.2 mV and 18.1 ± 0.5 mV were obtained by self-assembly in PBS solution under intensive stirring. The incorporation of PEG-C diblock copolymers resulted in an increase of particle size, however no specific relation between composition, size, and polydispersity was observed. In case of PEG-CG diblock copolymers a rather systematic increase of the particles’ size with increasing content of diblock copolymer was shown. Furthermore, with a decrease of content of diblock copolymer in the particle structure zeta potential strongly increased. Additionally, the content of glycolide units in triblock copolymer increased the zeta potential of PEI-CG-PEI-based particles in comparison to PEI-C-PEI-based ones. Therefore, obtained particles could be used as potential target-oriented polycationic macromolecules for carrier systems.