Crosslinked hyaluronic acid gels with blood-derived protein components for soft tissue regeneration.

Hyaluronic acid (HA) is an ideal initial material for preparing hydrogels, which may be used as scaffolds in soft tissue engineering based on their advantageous physical and biological properties. In the present study, two crosslinking agents: divinyl sulfone and butanediol diglycidyl ether were used to investigate their effect on the properties of HA hydrogels. As HA hydrogels alone do not promote cell adhesion on the scaffold, fibrin and serum from platelet-rich fibrin were combined with the scaffold, the aim was to create a material intended to be used as soft tissue implant that facilitates new tissue formation, and degrades over time. The chemical changes were characterized and cell attachment capacity of the protein containing gels was examined using human mesenchymal stem cells, viability was assessed using live-dead staining. FTIR measurements revealed that linking fibrin into the gel was more effective than linking SPRF. The scaffolds were found to be able to support cell adherence onto the hydrogels, and the best result was achieved when HA was crosslinked with divinyl sulfone and contained fibrin. The most promising derivative, 5 % DVS crosslinked fibrin containing hydrogel was injected subcutaneously into C57BL/6 mice for 12 weeks. The scaffold was proven to be biocompatible, remodeling, and vascularization occurred, while shape and integrity were maintained.