Research Terms
This bioreactor system can subject cells to independently-controlled amounts of fluid flow, pressure, and other variable forces, permitting in-vitro study of the cellular responses to multiple mechanical stimuli. Bioreactors are manufactured devices used in cell culture and tissue creation; applying chemical and mechanical stimuli allows lab researchers to guide cell structure, organization, and function. However, available bioreactor devices are costly, complex, and typically not user-friendly. Most bioreactors cannot test multiple conditions on a single device, highlighting a need for a low-cost, accessible, and high-throughput system.
Researchers at the University of Florida have developed a bioreactor system that stimulates cells through a combination of mechanical forces. A collection of sensors allows for real-time, automatic adjustments of the stimuli experienced by the cell cultured in the device, permitting researchers to study the effects of mechanical forces on cellular systems.
Automated bioreactor system that applies a range of variable mechanical forces for cell culture study
A silicone chamber, flow circuit, support structure, control system, and multi-channel peristaltic pump form the bioreactor system. The chamber connects to a linear actuator that strains the chamber and pulls each end in unison. A bi-directional lead screw synchronizes the linear actuator’s pulling. 3D natural or synthetic hydrogels fill a specific region intended for cell culture, decoupling its properties from the chamber’s overall material properties. The chamber design facilitates the application of mechanical stimuli on cells cultured in the device. A collection of sensors also allows real-time adjustment of the device’s peristaltic pump and actuators to vary a range of mechanical forces.
This biomaterial combining a DNA-collagen complex with magnetoelectric fibers can enable a variety of tissue-regenerative biomedical applications. Analysts project the global market for tissue regeneration biomaterials to exceed $149 billion by 2025 . Cross-linked collagen has many uses for biomedical tissue regeneration, making materials that restore skin, tendons, cartilage, and bone and help injuries heal quicker. However, cross-linking typically requires chemicals and additives that are toxic. Electric stimulation can promote the regeneration of several tissues including nerves, but standard techniques require electrical leads, which are too invasive to treat many injuries in vivo.
Researchers at the University of Florida have developed a composite of DNA-collagen and magnetoelectric nanofibers to use as a biomaterial for in vivo tissue regeneration. The collagen cross-links using DNA instead of toxic chemicals. This biomaterial allows delivery of electric fields from within the body to provide stimulation treatment without the use of invasive electrical leads.
Non-toxic, functionalized biomaterial that enables local neurite regeneration via non-invasive magnetoelectric stimulation
This composite material forms by combining magnetoelectric nanofibers with a complex of short, single-stranded DNA aptamers and collagen. The DNA aptamers are able to cross-link collagen to form a DNA-collagen complex. The complex can have different biological properties depending on the sequence of the aptamer, its geometry, and its concentration. This complex then mixes with an aqueous solution of magnetoelectric fibers, which can locally generate electric fields with the application of an external magnetic field. This allows the resulting fiber, nanoparticle, or 3D hydrogel biomaterial structure to deliver long term electric stimulation that promotes neurite regeneration without the use of invasive electrical leads.
This tissue production system generates fully functional tissues using a combination of nucleic acid-collagen complexes and elastin to form improved hydrogels. This combination allows generated tissues to have more natural function than those constructed using hydrogels without elastin and allows for a greater diversity of tissues, including bone. The tissue engineering market should exceed $6.8 billion by 2027 and continue growing2. However, current collagen hydrogels used to construct tissues have poor mechanical properties, limiting their functionality and the diversity of tissues they can construct.
Researchers at the University of Florida have developed a tissue production system that combines nucleic acid-collagen complexes and elastin to control the mechanical properties of hydrogels used to construct bodily tissues. These nucleic acid-elastin-collagen complexes improve functionality of engineered tissues and enable mimicry of more tissue types in the body.
Tissue production using a combination of nucleic acid-collagen complexes and elastin to improve the mechanical properties of hydrogels and generate fully functional tissues.
Engineered tissues are promoted in hydrogels with improved mechanical properties using a combination of nucleic acid-collagen complexes and elastin. Collagen and elastin are natural components of the extracellular matrix providing much of the tissues’ overall mechanical properties. Modulation of these two components along with the DNA component allows the mechanical properties of nucleic acid-collagen complexes to be manipulated. Adjusting the mechanical properties of hydrogels allows for a greater range of tissues to be produced allowing the constructed tissues to achieve full natural function.
This injectable, self-assembled system mixes collagen and single-stranded DNA aptamers to form biologically functional materials. Many medical and cosmetic applications such as connective-tissue repair, drug delivery, gene delivery, wound healing, or skin care extensively use biocompatible collagen materials. Analysts project the collagen biomaterials market will exceed $5 billion by 2025. The collagen can be modified for physical and chemical properties in certain applications, but this usually involves chemicals that are cytotoxic and can cause calcification. Additionally, collagen materials often perform specific biological functions by incorporating additives, but these can cause damaging off-target effects.
Researchers at the University of Florida have developed an injectable, self-assembled system that uses DNA aptamers to stabilize collagen fibers in a 3D network mimicking the structure of native tissue. The choice of DNA aptamer can adjust fiber properties and drive the biological functions of collagen materials without side effect-causing additives.
Collagen materials enhanced without cytotoxic chemicals that achieve greater biological functionality to improve biomedical devices and cosmetic formulations
Short, single-stranded DNA aptamers bind to collagen proteins and act as 3D crosslinkers to promote fiber formation. Fibers begin to form spontaneously after combining DNA and collagen solutions. Different aptamer sequences, geometries, and concentrations result in different fiber properties, such as cellular affinity and biological activity. Because of DNA aptamers’ specificity, this facilitates the creation of collagen materials with greater biological functionality for applications in cosmetics and biomedicine.
This tissue fixation technique uses natural aldehyde alternatives, such as cinnamaldehyde solution or vanillin solution, to cross-link protein scaffolds, thereby increasing the viability of medical implants. Healthcare professionals in the medical device industry use protein-based implants for a variety of applications, such as wound healing or heart valve replacement. However, some techniques for stabilizing the proteins in medical prostheses are unsuitable for long-term use. The common fixative for heart valve implants, glutaraldehyde, can cause implant calcification and cell death. Additionally, available chemical fixatives for bioprosthetics can provoke an immune response, increasing the likelihood of implant rejection.
Researchers at the University of Florida have developed a procedure that stabilizes protein scaffolds in bioprosthetic implants. The protein fixative solution utilizes a non-synthetic aldehyde, reducing immunogenicity and toxicity and increasing the long-term stability of implanted medical devices.
Protein scaffold fixative that improves long-term viability of heart valves and other biomedical implants
Aromatic, natural aldehydes derived from cinnamon, cinnamaldehyde or vanillin combines with a non-toxic volatile solvent to create a solution. This solution, in either liquid or vapor phase, at various concentrations at room temperature, cross-links electrospun gelatin protein nanofibers, forming stable protein scaffolds. The resulting protein scaffolds are suitable for various tissue engineering and bioprosthetic applications.
These targeting agents use nucleic acid aptamers conjugated with magnetic nanoparticles to target cell surface receptors that make it possible to remotely control cell signaling for stem cell differentiation, apoptosis or tissue matrix production. Processes such as apoptosis, cell division, motility, stem cell differentiation and tissue formation are fundamental in cancer therapy and regenerative medicine, a rapidly expanding market due to industry-wide focus on organ and cartilage repair. The regenerative medicine market is expected to increase to $67.6 billion in 2020. Available technologies often use activating proteins on cell receptors, which diminish external control of activation and cell signaling. By bonding nucleic aptamers to magnetic particles, University of Florida researchers have designed molecules that can target very specific cell surface receptors in a controlled manner for stem cell differentiation, apoptosis and tissue matrix production. Aptamers target specific cell receptors and create a bond without activating the cell receptor. Conjugating the aptamers with a magnetic core allows for external control via magnetic fields and radiofrequencies. Ex vivo and in vivo tissue generation and stem cell therapies are likely products using this combination.
Nucleic aptamers/magnetic nanoparticle conjugates for remote control of cell signaling for stem cell differentiation, apoptosis and tissue matrix production
Magnetic control of cells and biological channels is helping advance regenerative medicine and tissue engineering. This combination of nucleic aptamers with magnetic nanoparticles heightens the ability to control those processes. Designed to target very specific receptors, the specially designed nucleic aptamers are ideal targeting molecules. Binding the aptamer to a receptor does not in itself activate the receptor, a drawback of proteins, peptides and antibodies typically used as targeting molecules. Once bonded to a magnetic core, the cell surface receptor and its associated signaling pathway is controllable via magnetic fields. Researchers are able to apply external static, high gradient magnetic fields or radiofrequency fields to activate cell surface receptors, remotely controlling cell signaling and association behaviors such as apoptosis, cell division, motility, stem cell differentiation and tissue formation.
