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This gentle decellularization process uses an apoptotic drug that enhances production of acellular scaffolds for tissue regeneration and nerve repair. Available technologies for obtaining tissue-specific scaffolds require large volumes of expensive detergents and multiple, time-consuming steps. The use of harsh detergents leads to the broad dispersal of intracellular components, disruption of tissue morphology, and removal of desired tissue elements. Furthermore, incorporating time-consuming steps keeps operation costs at a premium. By using an FDA-approved, commercially available, and inexpensive drug, researchers at the University of Florida have significantly reduced the operational costs of scaffold generation and increased manufacturing simplicity. Using this process, UF researchers have been successful in demonstrating the effective removal of cellular components from both peripheral nerve and nucleus pulposus of the intervertebral disc and preserving the tissue architecture and morphology more accurately than available technologies.
Mild process for drug-induced removal of unwanted cellular components during biomimetic scaffold generation
An apoptotic agent provides for the improved decellularization of prospective tissue scaffolds. The apoptotic agent’s exposure to tissues induces widespread apoptosis by prompting cellular deterioration and degradation of intracellular components and allocation of these degraded components into small particles, known as apoptotic bodies. Following simple removal of these apoptotic bodies, the resulting tissue structure is able to be employed as a scaffold substrate for improved 3-dimensional cell culture and tissue engineering.
These intelligent devices with integrated wireless drug delivery circuits and multiple on-chip antennas can change the treatment of diseases by facilitating the controlled release of therapeutic agents into specific tissues and the bloodstream. Drug delivery devices capable of precise, targeted control of levels of drugs are particularly useful in the treatment of many conditions including Alzheimer’s disease, cancer, diabetes, cardiovascular disease, pain, and infectious diseases. Available drug delivery devices use low frequency bands and large antennas that include the need to be tethered to stationary equipment and constant human intervention. University of Florida researchers have developed devices with integrated wireless drug delivery circuits and multiple on-chip antennas using frequency bands that allow for miniaturized, mobile solutions. Thus, the delivery of drugs becomes more feasible, because the device can be reduced to an implantable size if desired. This integrated drug delivery circuit allows drugs to be administered according to a schedule that corresponds to a patient’s rhythms in order to maximize effectiveness and minimize the side effects of the therapy.
Wireless control device for drug delivery applications
This wireless controller for electrochemically triggered drug delivery comprises electroactive polymer-based biomaterials. It includes an electroactive polymer cell, a wireless polymer conduction controller, and another wireless module that communicates with the controller device. A circuit or device integrates the electrochemical cell and wireless polymer conduction controller. The device executes essential operations such as controlling the wireless module and temperature sensor. The wireless module communicates with the device, receiving device information, device status, and temperature data. Using this data, the wireless module determines the duration and quantity of the drug that needs to be released.
This injectable minimally invasive treatment delivers enhanced secretome harvested from electrically stimulated cells to damaged tissue, thereby promoting tissue regeneration noninvasively. Biological cells and tissues produce a variety of proteins and molecular structures that are excreted into the extracellular space. These excreted molecules are collectively known as the secretome. Local electrical stimulation (E-stim) has shown to promote tissue regeneration, however delivering E-stim to many tissues in vivo remains overly invasive.
Researchers at the University of Florida have shown enhanced secretome from E-stim of donor cells, cell lines, or a patient’s own cells can be purified and concentrated for use as an injectable low-volume, low-risk therapeutic in tissue regeneration. This could also be combined with cell delivery methods, for a combinatorial approach. The global market for such tissue engineering is projected to exceed $11 billion by 2022. This technology also overcomes the detrimental immune response that can be elicited by large volume applications of current cell-based tissue regenerative therapeutics.
Injectable secretome harvested from electrically stimulated cells as a therapeutic for tissue regeneration and tissue engineering
This injectable composition delivers enhanced secretome to damaged tissue to stimulate tissue regeneration and healing. Specific cells isolated from a variety of species depending on the target organ or tissue undergo electrical stimulation for a period of at least 24 hours in vitro. The electrical pulses promote cell secretome production and enhance the proteins, growth factors, and other molecules in the secretome. Controlling the electrical stimulation may tune the secretome for specific regenerative applications. Once isolated and collected, the secretome combines with an injectable hydrogel, forming a delivery system that localizes the secretome at the site of the damaged tissue following injection.
This injectable hydrogel nerve graft encourages neuronal repair and regeneration at the site of a peripheral or central nervous system injury. Tissue engineering therapies utilize implanted scaffolds to guide tissue regeneration, and tissue-specific scaffolds with the native extracellular matrix (ECM) protein environment do so most effectively. Nerve tissue scaffolds can help regenerate damaged neural tissue or deliver therapeutics to treat peripheral nerve and spinal cord injuries. These scaffolds must be free of cellular components to prevent immune rejection. However, standard decellularization steps use chemicals and harsh washings that damage ECM proteins and native tissue structure, limiting a scaffold’s regenerative capacity.
Researchers at the University of Florida have developed an injectable hydrogel derived from decellularized peripheral nerve tissue that encourages regeneration in the nervous system. This hydrogel could support cell viability, and thus could be a cell carrier for cell transplantation into the spinal cord (and possibly for other tissue applications). It could also serve as an ideal substrate for cell delivery, enhancing cell survival and cell localization at the injection site. The decellularization process utilizes apoptosis to ensure that the resulting nerve scaffold maintains the ECM proteins and mechanical properties of the native tissue.
Tissue-specific extracellular matrix (ECM) hydrogel that is injected into the site of a spinal cord or peripheral nerve injury to form a scaffold for nerve regeneration therapy
The injectable nerve scaffold is a hydrogel that gels in situ consisting of the extracellular matrix (ECM) protein structure of decellularized peripheral nerves. Decellularization of the tissue is mediated through apoptosis that causes organized fragmentation of cells, allowing for easy cell removal without detergents. This process causes less damage to the extracellular matrix (ECM) components in the nerves and takes less time. Enzymes solubilize the decellularized nerves into a liquid solution, which can then gel into the various non-uniform shapes of injury sites to support neuronal regeneration.
Biodegradable supramolecular polymers that receive and transmit electrochemical information may be employed for efficient and effective medicinal treatment. Targeted drug delivery (occasionally employing stimuli-responsive materials) has been effectively utilized since the early 2000s for such life-threatening illnesses as cancer, Alzheimer’s disease, epilepsy, and cardiovascular disease; however, available electroactive polymers for controlled drug delivery have failed to be completely biodegradable and often required the aid of a toxic oxidizer during the drug-doping process. Researchers at the University of Florida have discovered a fully biodegradable, conductive polymer that may prove extremely beneficial to modern medicine. This polymer does not require the presence of a toxic oxidizer and completely breaks down due to the action of naturally occurring enzymes in the body. The complete biodegradation of the product would eliminate common problems associated with polymer residue in the body, including inflammation and infection, and the controlled application of electric stimulation would allow for time-sensitive treatment of target cells.
Polymers that naturally breakdown in the body upon the application of an electrical potential in order to optimize drug delivery and disease treatment
These fully biodegradable polymers discovered by researchers at the University of Florida would be able to administer a specific amount of drug at a specific time interval based on the electrochemistry of the surrounding cell environment and the applied stimulus of an external electrode. The biodegradable polymer would be composed of alternating water soluble electrochemically responsive units and alcohol-terminated diols, thus forming ester bonds that can be easily broken down by enzymes in living systems. The broken down fragments would be small enough to exit the bloodstream through the renal filtration system, rendering the technology fully degradable. Existing "biodegradable" technologies do not fully breakdown into fragments removable by the body.
This biomaterial composed of electroactive polymers utilizes electrical stimulation of cells to promote nerve regeneration within the peripheral nervous system. The field of regenerative medicine continually attracts increasing attention from investors and industries, surpassing $1 billion in annual revenue in 2013. Autografts, which take a functioning section of a nerve from elsewhere in the patient’s body, and allografts, which use a section of nerve form another living organism or cadaver, are typically used in regenerative medicine to repair nerve defects. However, autografts can cause loss of function at the removal site, and allografts are expensive. Researchers at the University of Florida have developed an electroactive biomaterial for peripheral nerve regeneration that uses electrical stimulation to encourage cells to increase nerve growth factor production, which is known to be beneficial for central and peripheral nervous systems. This biomaterial is a cheap alternative to typical non-electroactive nerve conduits, broadening its potential use to a wider population. These electroactive biomaterials also have the potential to be used to deliver drugs, antibacterial agents, and antifungal agents. Because these electroactive polymers use electrical stimulation, this biomaterial can be applied not only to nerve tissue but also cardiac, bone, and muscle tissues.
Electroactive biomaterial with electrical stimulation promotes nerve growth
This electroactive tissue scaffold comprises biodegradable polymers that enable the electrical stimulation of cells cultured thereon or therein. Such scaffolds may exhibit small changes in size or shape when stimulated by an electric field, thereby enabling drug delivery from the polymer matrix. Specifically, the biodegradable polymer-based scaffold with an interpenetrating network of electroactive polymers can be used as scaffolds to culture Schwann cells. Schwann cells are found throughout the entire peripheral nervous system and increase the production of nerve growth factor when electrically stimulated; importantly, nerve growth factor promotes nerve regeneration. Thus, this tissue scaffold may be used to deliver nerve growth factor to nerve tissue by implanting in the tissue a scaffold with cultured Schwann cells and applying electrical stimulation. These scaffolds also hold promise as drug delivery, antibacterial, and antifungal agents and are potentially capable of mechanotransduction of stem cells.
These magnetically templated tissue engineering scaffolds for biomedical applications, particularly as nerve guides for peripheral nerve injury repair. Peripheral nerve injuries (PNI) have a significant socioeconomic impact, resulting in over 8 million restricted activity days and over 5 million disability days per year. Over 200,000 PNI repair procedures are performed yearly in the U.S., with an estimated market for transected peripheral nerve injury repair of about $1.32-$1.93 billion. The current approach for repairing nerve injuries with gaps greater than 2 cm is autografts, commonly from the patient’s sural nerve. However, autografts have significant morbidity and functional deficit at the donor site, are not readily available, and matching the size of the donor nerve to the repaired nerve is often difficult. In addition, studies indicate motor function recovery occurs in only 40 to 50 percent of patients. A need exists for a bioengineered peripheral nerve scaffold with architectural and chemical components of natural peripheral nerve tissue, facilitating the repair of any size nerve gaps.
Researchers at the University of Florida have developed magnetically templated, biocompatible tissue engineering scaffolds, with aligned porosity with dimensions greater than 2 cm, for tissue growth and repair, including peripheral nerve repair. The magnetic particles can control the direction and extent of the aligned pores and channel structures of the scaffolds, allowing for peripheral nerve injury repairs of more considerable distances.
Magnetically template tissue engineering scaffolds with aligned pores and channels for tissue growth and repair, including peripheral nerve repair
These magnetically templated tissue scaffolds use magnetic nanoparticles encapsulated in a dissolvable, biocompatible matrix material. The influencing magnetic field causes the microparticles to align, forming a plurality of lines and columns that are spatially aligned. The scaffolding material crosslinks and polymerizes to form a solid, three-dimensional scaffold structure around the nanoparticles. The magnetic nanoparticle matrix then dissolves to produce aligned voids and microchannels, with aligned porosities with dimensions greater than 2 cm within the scaffold, allowing for nerve repair of greater distances.
PRUITT FAMILY DEPT OF BIOMEDICAL ENGINEERING P.O. BOX 116131 GAINESVILLE, FL 32611-6131
