Mapping Glycosaminoglycan–Hydroxyapatite Colloidal Gels as Potential Tissue Defect Fillers

[Image: see text] Malleable biomaterials such as Herschel–Bulkley (H–B) fluids possess shear responsive rheological properties and are capable of self-assembly and viscoelastic recovery following mechanical disruption (e.g., surgical placement via injection or spreading). This study demonstrated that the addition of moderate molecular weight glycosaminoglycans (GAGs) such as chondroitin sulfate (CS) (M(w) = 15–30 kDa) and hyaluronic acid (HA) (M(w) = 20–41 kDa) can be used to modify several rheological properties including consistency index (K), flow-behavior index (n), and yield stress (τ(y)) of submicrometer hydroxyapatite (HAP) (D(avg) ≤ 200 nm) colloidal gels. GAG–HAP colloidal mixtures exhibited substantial polymer–particle synergism, likely due to “bridging” flocculation, which led to a synergistic increase in consistency index (K(GAG-HAP) ≥ K(GAG) + K(HAP)) without compromising shear-thinning behavior (n < 1) of the gel. In addition, GAG–HAP colloids containing high concentrations of HAP (60–80% w/v) exhibited substantial yield stress (τ(y) ≥ 100 Pa) and viscoelastic recovery properties (G′(recovery) ≥ 64%). While rheological differences were observed between CS–HAP and HA–HAP colloidal gels, both CS and HA represent feasible options for future studies involving bone defect filling. Overall, this study identified mixture regions where rheological properties in CS–HAP and HA–HAP colloidal gels aligned with desired properties to facilitate surgical placement in non-load-bearing tissue-filling applications such as calvarial defects.