Effect of Entrapped and Free Calcium Hydroxyapatite Particles on Rheological Properties of Hyaluronic Acid–Calcium Hydroxyapatite Composite Hydrogels

Abstract

Injectable hydrogels are intensely studied for biomedical and cosmeceutical applications where a polymer matrix is cross-linked to incorporate therapeutic molecules or particles and injected to achieve drug delivery, tissue regeneration, skin wound healing, etc. However, to realize these potential applications, a deeper understanding of rheological and viscoelastic behaviors of the hydrogel systems and matrix-particle interactions is required for future formula optimization and product development. To fill this gap, in the present work, we prepared chemically cross-linked hyaluronic acid (HA) and incorporated calcium hydroxyapatite (CaHA) particles to fabricate HA-CaHA hydrogel composites. CaHA fillers were integrated into the HA network before or after the cross-linking reactions to create either entrapped (before cross-linking) or free (after cross-linking) particles, and the resultant specimens were analyzed with various rheological tests to investigate their effects on the viscoelasticity, creep recovery, yield stress, and flow behaviors of the overall HA-CaHA hydrogel composites. To the best of our knowledge, the preparation of biopolymer-based injectable hydrogels incorporating both entrapped CaHA and free CaHA particles has not been reported by far. The present work not only provides a systematic rheological profile of HA-CaHA injectable hydrogels but also investigates the influence of two types of CaHA particles on the overall viscoelastic and rheological properties of the hydrogel system. The results will present crucial information to support future optimizations in hydrogel design, biomaterial selection, and structural analysis for various wet soft materials with promising biomedical and cosmaceutical applications.