Medical Devices : Device coatings

Medical Devices Portfolios


Modular Peptide Binds to Bone and Improves Graft Osteoinductivity

UW–Madison researchers and others have developed a novel approach for linking growth factors to the mineral component of bone. Their approach uses a modular peptide design with two functional units: a biologically active growth factor portion that can stimulate osteogenesis, angiogenesis or osteogenic differentiation, and a binding portion that improves the non-covalent binding of the peptide to the surface of native bone. These modular peptides can be used to coat, or ‘decorate,’ natural bone tissues, providing an improved method of delivering growth factors to skeletal defects.

Regulating Stem Cell Behavior with High Throughput Mineral Coatings

UW–Madison researchers have developed methods of non-viral cell transfection and regulating cell behavior using mineral coatings. The coatings bind polynucleotides and provide a source of calcium and phosphate ions to enhance transfection.

More specifically, a mineral coating is formed by incubating a substrate in a simulated body fluid (SBF). The substrate then is loaded with a polynucleotide (e.g., plasmids, mRNA or proteins), which binds to the coating. Next, a solution of cells is deposited and cultured until a desired level of transfection occurs.

Device Coating Can Selectively Bind and Deliver Biologics

UW–Madison researchers have developed coated devices that bind and deliver selected biological molecules from bodily fluids like platelet rich plasma. The methods may be carried out during surgery and used to isolate molecules from a patient’s own body.

Suitable devices include films, meshes, injectable particles or common orthopedic devices (pins, nails, plates, sutures, etc.). A coating containing phosphate, calcium or another mineral is applied under physiological temperature and pH, resulting in a structure suitable for protein binding. The device then is incubated in bodily fluid long enough to allow the biological molecule of interest to attach to the mineral coating. A suitable ionic buffer helps selectively isolate the desired molecule.

The biologic-containing device is rinsed of unwanted material and implanted into a subject. The rate at which the coating degrades can be modified to control the release of the molecules.

Multilayered Films for the Controlled Release of Anionic Molecules, Including Nucleic Acids

UW–Madison researchers now have developed PEMs that incorporate cationic charge shifting polymers to promote the controlled release of multiple different anionic molecules with distinct release profiles.  The use of these charge dynamic polymers enables more sophisticated and tunable control of biomolecule release than other types of degradable layers and allows the fabrication of ultrathin films that can sustain the release of nucleic acids for variable periods of time ranging from several days to several weeks or months.  For example, a single multilayered film could be used for the rapid, short-term release of a first DNA construct followed by the long-term release of a second, different DNA construct.

Bone Tissue Regeneration System That Provides Spatial and Temporal Control Over the Release of Growth Factors

UW–Madison researchers have developed a tissue regeneration system that utilizes porous scaffolds to localize and temporally control the release of multiple growth factors.  In this system, porous beta tricalcium phosphate (β-TCP) templates are coated with one or more extracellular matrix layers.  The layers include at least one thin, degradable mineral layer that is similar to bone mineral.  Because the coating process does not require high temperatures or organic solvents, biologically active growth factors such as vascular endothelial growth factor (VEGF) and bone morphogenetic protein-2 (BMP-2) can be incorporated in the layers. 

To control dissolution order, and ultimately, delivery of the biologically active molecules, multiple distinct layers are deposited on the β-TCP scaffold.  Each layer may contain one or more active biomolecules and is designed to dissolve at a separate rate. As the matrix material gradually breaks down, the growth factors are delivered sequentially.  This provides temporal control of growth factor signaling, thereby directing the activities of associated cells, to enable the growth of new bone tissue.

Modular Peptide Binds to Biomaterials and Promotes New Bone Formation

UW–Madison researchers have developed a novel approach for linking growth factors to the surface of an HA-coated biomaterial.  Their approach uses a modular peptide design with two functional units: a biologically active growth factor portion that can initiate osteogenesis, angiogenesis or osteogenic differentiation and a binding portion that improves the non-covalent binding of the peptide to “bone-like” HA-based biomaterials.  These modular peptides can be used to coat, or “decorate,” biomaterials, providing an improved method of delivering growth factors to skeletal defects.

Biologically Active Sutures Enhance Tissue Healing Following Surgical Procedures

UW-Madison researchers have developed a method of coating the surface of commonly used suture materials and other orthopedic devices with a biodegradable layer containing molecules that can induce tissue growth and limit bacterial infection.  The rate at which the coating degrades can be modified to control the release of the molecules. 

Specifically, a suture is coated with a mineral layer under physiological temperature and pH, resulting in a nano-porous structure with high surface area for protein binding.  Then biologically active molecules are bound to the surface of the suture for subsequent release in vivo.  Protein binding can be achieved rapidly in the operating room, and the process can be adapted to enable the incorporation of a wide range of other therapeutic molecules, in addition to proteins.

Layer-by-Layer Covalent Assembly of Reactive Ultrathin Films

UW–Madison researchers have developed robust methods for the layer-by-layer fabrication of covalently cross-linked ultrathin films.  This approach makes use of fast and efficient “click”-type interfacial reactions between poly(2-alkenyl azlactone)s and appropriately functionalized polyamines.  In contrast to conventional, aqueous methods for the layer-by-layer fabrication of thin films, fabrication of these ultrathin films occurs in organic solvents and is driven by rapid formation of covalent bonds during assembly. This approach also yields films with residual azlactone groups that can be used to tailor the surface properties of the films by treatment with a broad range of chemical and biological functionalities.

An Orthopedic Implant Coating for Enhanced Bone Growth

UW-Madison researchers have developed a biomaterial-based approach for directing bone regeneration to treat bony defects. This approach uses a biologically active calcium phosphate-based coating to target and control delivery of a bound growth factor molecule capable of inducing bone growth. This coating can be applied to all bioresorbable materials commonly used in orthopedic surgery, including nails, pins, anchors, screws, plates and scaffolds.

Under physiological conditions, the solubility of different calcium phosphate materials can vary by more than 5000 percent. To take advantage of this broad range of dissolution rates, the coating consists of several layers of calcium phosphate materials with distinct dissolution profiles. Bone growth factors are bound to the calcium phosphate and released based on the dissolution profile of each layer. To provide a delayed release, calcium phosphate layers that do not contain a growth factor or drug can be incorporated into the coating. This approach can be easily integrated with existing implants and surgical procedures in clinics.

Multilayered Film for Delivering Proteins and Other Small Molecules into Cells

UW-Madison researchers have developed a new way of delivering proteins and other small molecules into cells. This approach uses a cationic “anchor” to improve incorporation of proteins into multilayered films.

Before the protein or small molecule is integrated into the film, a cationic protein transduction domain, such as nonaarginine, is attached to it. Appending short, cationic peptides or oligomers to proteins can facilitate their layer-by-layer assembly into PEMs, as well as their uptake by cells.

Then the cationic molecule is incorporated into a polyelectrolyte multilayered film, along with anionic polymers such as sodium polystyrene sulfonate, to result in a multilayered assembly that is preferably about 80 nanometers thick. When this composition is presented to a cell, the film dissolves, delivering the molecule to the cell.

Localized Delivery of Nucleic Acid by Polyelectrolyte Assemblies

UW-Madison researchers have developed ultrathin, multilayered polyelectrolyte films that permit the localized delivery of nucleic acids to cells from the surfaces of implantable materials. To form the polyelectrolyte coating, nucleic acids and polycations are deposited layer-by-layer onto the surface of an implantable device. After implantation, nucleic acids are delivered only to the cells in direct contact with the device surface. The polyelectrolyte film promotes the direct and self-sufficient transfection of those cells to enable local production of therapeutic agents.

Spatial Control of Signal Transduction

UW-Madison researchers have developed a novel approach for the delivery of growth factors and other biologically active signaling molecules that allows for spatial control of signal transduction. Molecular handles (e.g., peptides or oligonucleotides) with an affinity for growth factors or other signaling molecules are attached to specific locations on a surface or within a matrix. The surface or matrix includes a translucent, biologically inert polymer backbone. Signaling molecules are drawn to the precisely desired location of the substrate or matrix by associating specifically, reversibly and non-covalently with the handles. The affinity of the molecular handle for the signaling molecule is tailored so that it selectively attracts the growth factor but does not bind so tightly that it blocks interaction of the growth factor with percursor cells. The signaling molecules can then be presented to precursor cells in locally high concentrations, mimicking complex developmental processes like organogenesis, which is particularly important in stem cell-based approaches to tissue regeneration.

Improved Magnetic Resonance Signal Emitting Coatings

The UW-Madison researchers have now improved the original technique by encapsulating the coating materials – a polymer complex composed of paramagnetic metal ions and a chelation agent – in a hydrogel prior to applying the coating to a medical device. They demonstrated that the hydrogel reduces the mobility of the paramagnetic ion/chelation agent complex, resulting in an enhanced MRI signal from the coated device.

MR Signal-Emitting Coatings for Devices Used in Therapeutic MRI Applications

UW-Madison researchers have developed a process and a polymer for coating medical devices so they can be readily visualized with MRI during therapeutic procedures. The polymeric coating contains paramagnetic ions that cause it to strongly emit MR signals. The MR-signal emitting coatings are applied to a medical device by first plasma-treating the surface of the device to carry functional groups; binding a chelating agent to the functional groups; and coordinating a paramagnetic metal ion, such as gadolinium (III), with the chelating agent.