Kelly R. Kirker

Cross-linked hyaluronic acid hydrogel films: new biomaterials for drug delivery.

A new hyaluronic acid (HA)-based hydrogel film was prepared and evaluated for use in drug delivery. This biocompatible material crosslinks and gels in minutes, and the dried film swells and rehydrates to a flexible hydrogel in seconds. HA was first converted to the adipic dihydrazide derivative and then crosslinked with the macromolecular homobifunctional reagent poly(ethylene glycol)-propiondialdehyde to give a polymer network. After gelation, a solvent casting method was used to obtain a HA hydrogel film. The dried film swelled sevenfold in volume in buffer, reaching equilibrium in less than 100 s. Scanning electron microscopy (SEM) of the hydrogel films showed a condensed and featureless structure before swelling, but a porous microstructure when hydrated. The thermal behavior of the hydrogel films was characterized by differential scanning calorimetry. The enzymatic degradation of the HA hydrogel films by hyaluronidase was studied using both SEM and a spectrophotometric assay. Drug release from the hydrogel film was evaluated in vitro using selected anti-bacterial and anti-inflammatory drugs. This novel biomaterial can be employed for controlled release of therapeutic agents at wound sites.

Attachment of hyaluronic acid to polypropylene, polystyrene, and polytetrafluoroethylene

Surfaces of polypropylene (PP), polystyrene (PS) and polytetrafluoroethylene (PTFE) were activated with radio frequency plasmas Ar and NH3 to aminate the polymer surface and were subsequently reacted with hyaluronic acid (HA) in one of the three different attachment schemes. Results show that ammonia plasma treated polymers were more reactive toward HA attachment. The three chemistry schemes consisted of two distinct approaches: (1) direct attachment of the HA to the aminated surface, and (2) extending the reactive group away from the surface with succinic anhydride and then reacting the newly formed carboxylic acid group with an adipic dihydrazide modified HA (HA-ADH). The latter scheme proved to be more effective, suggesting that steric effects were involved with the reactivity of the HA with surface groups. These HA-coated polymers are a candidate for cell attachment and growth.

Injectable synthetic extracellular matrices for tissue engineering and repair.

The development of novel biointeractive hydrogels for tissue engineering1, 2, 3, tissue repair, and release of drugs4 and growth factors5 has attracted considerable attention over the past decade. Our attention has focused on hydrogels based on the extracellular matrix (ECM), a heterogeneous collection of covalent and noncovalent molecular interactions comprised primary of proteins and glycosaminoglycans (GAGs)6. In the ECM, covalent interactions connect chondroitin sulfate (CS), heparan sulfate (HS) and other sulfated GAGs to core proteins forming proteoglycans (PGs). Noncovalent interactions include binding of link modules of PGs to hyaluronan (HA), electrostatic associations with ions, hydration of the polysaccharide chains, and triple helix formation to generate collagen fibrils.

Chondroitin Sulfate Hydrogel and Wound Healing in Rabbit Maxillary Sinus Mucosa

Objectives/Hypothesis: Chondroitin sulfate (CS) is a glycosaminoglycan in the extracellular matrix of all vertebrates. A biocompatible, nonimmunogenic, pliable hydrogel preparation of CS has recently been produced and has shown benefit in wound healing in murine and porcine epidermis. The objective of the current experiment is to compare the wound healing properties of CS hydrogel versus no treatment in wounds of the maxillary sinus mucosa.

Glycosaminoglycan Hydrogels as Supplemental Wound Dressings for Donor Sites

Chemically crosslinked glycosaminoglycan (GAG) hydrogel films were evaluated as biointeractive dressings in a porcine model for donor-site autograft wounds. Multiple 5 x 5 x 0.03 cm wounds were created on the dorsum of pigs. Half of the wounds were treated with a GAG film plus an occlusive dressing (Tegaderm), whereas the other half were treated with Tegaderm alone. At 3, 5, or 7 days after surgery, the partially healed wounds were excised and evaluated histologically for three animals at each time point. By day 3, epithelial cells had proliferated and migrated from wound edges and from epithelial islands associated with residual hair follicles to begin to cover the wound bed. A statistically significant increase in coverage was observed for GAG + Tegaderm-dressed wounds than for those with Tegaderm alone at day 3 and day 5 post-surgery. By day 7, all treatment groups were completely healed. Thus, GAG hydrogels accelerated wound healing by enhancing re-epithelialization.

HYALURONAN BIOMATERIALS FOR TARGETED DRUG DELIVERY AND WOUND HEALING

ABSTRACT A mild chemical modification of hyaluronic acid (HA) provides functionalized derivatives for fabrication of targeted drug delivery systems, wound dressings, tissue engineering scaffolds, and probes for cellular binding and transport of HA. First, we describe the use of covalent HA-anti-cancer agents for use as potential therapeutics. Data from cell culture, flow cytometry, and in vivo mouse models support this targcted anti-tumor strategy. Second, we describe new flexible hydrogel films composed of crosslinked chondroitin sulfate (CS) and HA, which have potential as wound dressings capable of biointegration and drug release. Lyophilization and rehydration of these flexible films also provide porous materials for cell growth and tissue engineering. Third, we describe progress on the elucidation of the structure determination of the HA-binding domain (HABD) of RHAMM and the use of this domain to identify peptides that mimic HA.

HYALURONIC ACID HYDROGEL FILM: A NEW BIOMATERIAL FOR DRUG DELIVERY AND WOUND HEALING

ABSTRACT A new hyaluronic acid (HA)-based hydrogel film was developed and evaluated for use in drug delivery and wound healing. This biocompatible material crosslinks and gels in minutes, and the dried film swells and rehydrates to a flexible hydrogel in seconds. HA was first converted to the adipic dihydrazide (ADH) derivative and then crosslinked with the macromolecular homobifunctional reagent poly(ethylene glycol)-propiondialdehyde (PEG-diald) to give a polymer network. After gelation, a solvent casting method was used to obtain an HA hydrogel film. The dried film swelled sevenfold in volume in buffer, reaching equilibrium in less than 100 sec. Scanning electron microscopy (SEM) of the hydrogel films showed a condensed and featureless structure before swelling, but a porous microstructure when hydrated. The thermal behavior of the hydrogel films, characterized by differential scanning calorimctry, indicated that the crosslinking of the two polymers clearly produced a new material having a microstructure different from either of its two components. The in vitro enzymatic degradation of the HA hydrogel films by hyaluronidase (HAse) was also studied using SEM. Drug release from the hydrogel film was also evaluated in vitro using selected anti-bacterial and anti-inflammatory drugs. This novel biomaterial can be employed for controlled release of therapeutic agents at wound sites.