Strong and Biostable Hyaluronic Acid–Calcium Phosphate Nanocomposite Hydrogel via in Situ Precipitation Process

Abstract

Hyaluronic acid (HAc) hydrogel exhibits excellent biocompatibility, but it has limited biomedical application due to its poor biomechanical properties as well as too-fast enzymatic degradation. In this study, we have developed an in situ precipitation process for the fabrication of a HAc-calcium phosphate nanocomposite hydrogel, after the formation of the glycidyl methacrylate-conjugated HAc (GMHA) hydrogels via photo-cross-linking, to improve the mechanical and biological properties under physiological conditions. In particular, our process facilitates the rapid incorporation of calcium phosphate (CaP) nanoparticles of uniform size and with minimal agglomeration into a polymer matrix, homogeneously. Compared with pure HAc, the nanocomposite hydrogels exhibit improved mechanical behavior. Specifically, the shear modulus is improved by a factor of 4. The biostability of the nanocomposite hydrogel was also significantly improved compared with that of pure HAc hydrogels under both in vitro and in vivo conditions.

Long-lasting and bioactive hyaluronic acid-hydroxyapatite composite hydrogels for injectable dermal fillers: Physical properties and in vivo durability

“…46 In our previous study, the degradation profiles and volume persistence of HAc and HAc-HAp composite hydrogels were found to be associated with swelling capacity. 38 Additionally, the in vitro enzymatic degradation behavior of HAc-microHAp and HAc-nanoHAp was also observed in comparison with that of pure HAc after all hydrogels were soaked in 1 U/ml hyaluronidase solution for 24 h (data not shown). In vitro stability of the hybridized hydrogels appeared consistent with their in vivo stability, where both HAc-microHAp and HAc-nanoHAp maintained their original shape with gradual decrease in size as opposed to pure HAc.…”

“…In particular, nano-sized HAp tightly bonded to the HAc surface, which limited the movement of HAc chains and reduced the swelling capacity. 38 The reduced swelling eventually results in increased stiffness of the fillers; thus, HAc-HAp composite fillers exhibit stronger performance than pure HAc owing to a decreased water uptake capacity…”

3D printing of hydrogel composite systems: Recent advances in technology for tissue engineering

“…Compared with same concentration of pre-mixed CaP nanoparticles, precipitated HAc-CaP composite hydrogels exhibited homogeneous distribution and approximately five times higher storage moduli values. In addition, mechanical properties were continuously increased by increasing concentration of precipitated CaP up to 40 wt% [15] . Very recently, Egorov et al combined in situ mineralization with 3D printing in which calcium chloride and ammonium hydrogen phosphate solutions were mixed with sodium alginate slurry and then 3D-bioplotter printing was employed to fabricate a cubic-shaped 3D composite structure (8 × 8 × 5 mm).…”

“…Conventional inorganic reinforcements are based on physical interactions with the hydrogel matrix in which secondary or van der Waals forces including London dispersion forces, dipolar interactions and hydrogen bonding are involved [14] . These physical interactions generate strong adhesion between the reinforcements and hydrogel matrix, and the enhancement of hydrogel properties are dependent on the amount of reinforcements and the volume ratio of physically interacted-and non-interacted-polymer networks [15] . In the case of chemical modifications, the introduction of chemical groups and the covalent bonding formations at the interface induce superior interfacial bonding strength of which energy is generally in between the 40 to 400 kJ/ mol i.e.…”

“…In the case of chemical modifications, the introduction of chemical groups and the covalent bonding formations at the interface induce superior interfacial bonding strength of which energy is generally in between the 40 to 400 kJ/ mol i.e. much higher than physical interaction (8)(9)(10)(11)(12)(13)(14)(15)(16) kJ/ mol) [14] . Thus, it is possible to provide substantial increase of mechanical strength to the hydrogel composite system.…”