Molecularly Imprinted Macroporous Hydrogel Promotes Bone Regeneration via Osteogenic Induction and Osteoclastic Inhibition.

Macroporous hydrogels offer physical supportive spaces and bio-instructive environment for the seeded cells, where cell-scaffold interactions directly influence cell fates and subsequently affect tissue regeneration post-implantation. Effectively modifying bioactive motifs at the inner pore surface provides appropriate niches for cell-scaffold interactions. A molecular imprinting method and sacrificial templates are introduced to prepare inner pore surface modification in the macroporous hydrogels. In detail, acrylated bisphosphonates (Ac-BPs) chelating to templates (CaCO3 particles) are anchored on the inner pore surface of the methacrylated gelatin (GelMA)-methacrylated hyaluronic acid (HAMA)-poly (ethylene glycol) diacrylate (PEGDA) macroporous hydrogel (GHP) to form a functional hydrogel scaffold (GHP-int-BP). GHP-int-BP, but not GHP, effectively crafts artificial cell niches to substantially alter cell fates, including osteogenic induction and osteoclastic inhibition, and promote in situ bone regeneration. These findings highlight that molecular imprinting on the inner pore surface in the hydrogel efficiently creates orthogonally additive bio-instructive scaffolds for bone regeneration.

Supramolecular self-assembled gold nanoparticle clusters for synergistic photothermal-chemo tumor therapy.

The combination of photothermal therapy and chemotherapy has emerged as a promising strategy to improve cancer therapeutic efficacy. However, developing a versatile nanoplatform that simultaneously possesses commendable photothermal effect and high drug encapsulation efficiency remains a challenging problem yet to be addressed. Herein, we report a facile supramolecular self-assembly strategy to construct gold nanoparticle clusters (AuNCs) for synergistic photothermal-chemo therapy. By utilizing the functional polysaccharide as a targeted ligand, hyaluronic acid-enriched AuNCs were endowed with targeting CD44 receptor overexpressed on the B16 cancer cells. Importantly, these hyaluronic acid modified AuNCs can shelter therapeutic cargo of doxorubicin (DOX) to aggregate larger nanoparticles via a host-guest interaction with the anchored ß-cyclodextrin, as a "nanocluster-bomb" (DOX@AuNCs). The in vitro results revealed that these DOX@AuNCs showed light-triggered drug release behavior and synergistic photothermal-chemo therapy. The improved efficacy of synergistic therapy was further demonstrated by treating a xenografted B16 tumor model in vivo. We envision that our multipronged design of DOX@AuNCs provides a potent theranostic platform for precise cancer therapy and could be further enriched by introducing different imaging probes and therapeutic drugs as appropriate suitable guest molecules.