Novel multifunctional PB and PBH hydrogels as soft filler for tissue engineering

In this study, we designed multifunctionalized hydrogel scaffolds and injectable particles based on high-molecular-weight (M_W) pullulan and human-like collagen (HLC) crosslinked with 1,4-butanediol diglycidyl ether (BDDE) for combination therapy tissue restoration. The properties of the pullulan/BDDE (PB) and pullulan/BDDE/human-like collagen (PBH) hydrogels were characterized via swelling ratio measurements, mechanical tests, and enzymatic degradation in vitro and via subcutaneous injections in vivo. The results demonstrate that the dry hydrogels completely returned to their original state in deionized water. The elastic modulus of the PBH53 dry hydrogels is higher than that of the other hydrogels after exposure to bending stress and compression stress with a maximum value of 7858.93 MPa. In addition, the in vitro live/dead staining and cell adhesion of the PBH hydrogels exhibited a superior fibroblast morphology without high levels of cell death, which were considerably better than those of PB hydrogels. In vivo, PB and PBH particles with good biocompatibility and anti-biodegradation were successfully prepared via the granulation of wet PB and PBH hydrogels for efficient subcutaneous injection in Kunming mice and New Zealand rabbits. Therefore, the PB and PBH hydrogels were found to be acceptable, safe, soft materials for use in skin restoration, cartilage treatment, and lacrimal dryness therapy.