Injectable Hydrogel-based Medical Devices: “There's always room for Jell-O”1
The human body is an intricate combination of hard and soft tissues, the interaction of which leads to its amazing flexibility and durability. To date, the vast majority of implantable biomedical devices use rigid materials composed of thermoplastics, epoxies and metals. The use of rigid materials has been very successful in some cases, such as total hip and knee replacements, in which the general strategy has been to engineer mechanical joints that can respond to the mechanical loads and biomechanics while minimizing wear. Currently missing from this strategy is the dynamic response of the soft tissue in joints, which provides conformable surfaces, improved comfort to the patient and potentially improved range of motion. Nature has already provided such a surface in the form of cartilage. Researchers have been striving to understand both the nature of cartilage and how to mimic it in a synthetic manner to allow the development of soft-solids biomedical implants for large and small joint applications. Additionally, approaches to reinforcing soft tissue require the use of a material with similar physical properties to native tissue, and preclude the use of rigid synthetic materials. Hydrogels are one possible solution.
Hydrogels in the Body
Nature has made extensive use of structured and inhomogeneous soft solids to provide vital roles. Mucus, vitreous humor, cartilage, tendons and blood clots are all forms of material known as hydrogels. Hydrogels are characterized as being neither solid nor liquid, but rather a combination of the properties of both. Structurally, a hydrogel is a 3-dimensional network of material that confines and supports water, but is not soluble in water, although the individual polymers that make up the hydrogel usually are. Hydrogels will typically contain between 50 percent to 90 percent water, depending on the formulation and degree of crosslinking. Gelatin is the most well-known example of a hydrogel, and is a proteinaceous structure derived from collagen extracted from animal tissue. The proteins form a 3-dimensional structure that are “crosslinked” together to yield the continuous, water-containing structure of the hydrogel. The vitreous humor of the eye and cartilage both contain protein hydrogels derived from collagen, which highlights that although chemically almost identical, markedly different properties can be obtained by varying the structure of the crosslinked network, ranging from a transparent low viscosity fluid to a tough, load-bearing construct.
The key to the success of hydrogels in the body is their viscoelasticity and permeability. Viscoelasticity is the behavior that results from being halfway between a rubber (in which energy put in is instantly restored – think of bouncing rubber balls) and water (in which inputted energy is lost to drag – think how fast a stone stops when it stops skimming). The crosslinked, polymeric structure of hydrogels results in an elastic response to rapid deformations, whereby the ability to transport fluid results in a compliant response to slow deformations, while still maintaining their shape over long periods. Viscoelasticity is one of the keys to cartilage’s success as a bearing surface. Cartilage is conformable under static loads, but maintains is shape and elasticity when subjected to impact loads. Viscoelasticity is not the only important property of cartilage, however. The hydrogel nature of cartilage results in the generation of a lubricating layer of fluid on the surface of the cartilage, thereby reducing the coefficient of friction on the bearing surface. Additionally, the permeability of hydrogels allows them to be populated by cells and transport nutrients and solutes across spaces in the body. Plasticized rubber, a synthetic engineering material, can have similar mechanical properties to cartilage, but is totally impermeable to aqueous-based fluids. Hence, it has neither the lubricating layer nor the ability to populate cells, both properties found in cartilage, which limits its utility in this application area. Synthetic hydrogels do have possibilities in this area.
Hydrogel formation can be grouped into two broad classes: those formed by chemical crosslinking, and those formed by physical bonds. Chemically-crosslinked hydrogels have an analogy to epoxies, which are 3-dimensional constructs typically made of hydrophobic polymers that have covalent bonds between chains. These hydrogels can be formed directly from monomers, which is how most contact lenses are manufactured, starting from monomers including vinyl pyrrolidone (NVP), methacrylic acid (MA) and poly-2-hydroxyethyl methacrylate (pHEMA). Alternatively, the hydrogel can be formed by crosslinking hydrophilic polymer chains with a crosslinking agent or by radiation, or by hydrolyzing a hydrophobic network. Another example is polyethylene glycol (PEG) which is often used for drug delivery applications.