Investigation of a Novel Cross-Linked Hyaluronan Hydrogel for Use as a Soft-Tissue Filler
Objective: To investigate an innovative tyramine-based hyaluronan (TB-HA) biomaterial for soft-tissue augmentation. Specifically, to test: (1) the ability of the TB-HA biomaterial to be injected subcutaneously; and (2) to test the in vivo response of the TB-HA biomaterial in an immunocompetent animal model. Introduction: Hyaluronan (HA) is a normal component of most tissues and, as such, is nonimmunogenic, nontoxic, and noninflammatory. Cross-linked hydrogels are formed from HA by substitution (approximately 5%) with tyramine followed by enzymatic cross-linking with peroxidase in the presence of very dilute hydrogen peroxide. From a single formulation of tyramine-substituted HA (TS-HA), a full spectrum of biomaterial properties can be produced by varying the HA concentration before cross-linking. The properties of these biomaterials ranged from a soft, optically clear hydrogel (6.25 mg/mL), suitable for soft-tissue augmentation as an injectable material, to a paste-like material (12.5–25.0 mg/mL). Materials and Methods: The hydrogel was evaluated in vivo as an injectable material (6.25 mg/mL). The material was injected into the subcutaneous tissue of an adult Sprague-Dawley rat, harvested at 8 weeks, and evaluated grossly and histologically. The specimens were paraffin embedded, sectioned on a microtome, and stained with hematoxylin and eosin. Results: In vivo analysis of the TB-HA hydrogels at 8 weeks revealed that they were resistant to degradation. Histological analysis revealed no evidence of rejection or tissue inflammatory response. Conclusions: Novel enzymatic cross-linking of HA enables the development of a versatile new biomaterial that can be used for soft-tissue augmentation. Preliminary in vivo analysis in an immunocompetent rat model revealed that the hydrogel material resisted degradation and did not elicit a host inflammatory response.