Injectable Host-Guest supramolecular hydrogel Co-Delivers hydrophobic and hydrophilic agents for enhanced wound healing

• A simple injectable hydrogel is formed through the host-guest interaction between F127 nanoparticle and α-CD. • The hydrogel simultaneously encapsulates hydrophilic bFGF and hydrophobic anti-inflammatory drug PNCB. • Both bFGF and PNCB can be released from the hydrogel in a controlled manner. • The hydrogel effectively promotes the skin wound healing in vivo by taking advantages of bFGF and PNCB. Achieving rapid healing of chronic wounds is still highly demanded. In the last few decades, exogenous administration of basic fibroblast growth factor (bFGF) in both clinical and preclinical investigations has proven to be therapeutically effective. However, the adverse wound environment (e.g., increased inflammation) deteriorates the functionality of bFGF. Therefore, improvements of the wound “soil” in addition to the use of bFGF is of importance to future clinical success. To address this issue, we designed an injectable host-guest drug delivery system for the controlled release of the hydrophilic bFGF alongside the hydrophobic anti-inflammatory drug, Pinocembrin (PNCB), to promote effective wound repair. The hydrophobic PNCB was first loaded into Pluronic F127 micelles (PNCB@F127) and then threaded onto bFGF-mixed α-cyclodextrin (α-CD) chains to form the host-guest hydrogel (P/bFGF@F127 α-CD ). The in vitro and in vivo results demonstrated that P/bFGF@F127 α-CD could effectively accelerate wound healing by combining the therapeutic effects of both PNCB and bFGF. The results showed the potential of combining anti-inflammatory drugs with growth factors for wound healing.