Administration of drugs via the buccal route has attracted much attention in recent years. However, developing systems with satisfactory adhesion under wet conditions and adequate drug bioavailability still remains a challenge. Here, we propose a mussel-inspired mucoadhesive film. Ex vivo models show that this film can achieve strong adhesion to wet buccal tissues (up to 38.72 ± 10.94 kPa). We also demonstrate that the adhesion mechanism of this film relies on both physical association and covalent bonding between the film and mucus. Additionally, the film with incorporated polydopamine nanoparticles shows superior advantages for transport across the mucosal barrier, with improved drug bioavailability (~3.5-fold greater than observed with oral delivery) and therapeutic efficacy in oral mucositis models (~6.0-fold improvement in wound closure at day 5 compared with that observed with no treatment). We anticipate that this platform might aid the development of tissue adhesives and inspire the design of nanoparticle-based buccal delivery systems.

Due to their high specific surface area, graphene oxide and graphene oxide-base nanoparticles have great potential both in dual-drug delivery and combination chemotherapy. Herein, we developed cisplatin (Pt) and doxorubicin (DOX) dual-drug-loaded PEGylated nano-graphene oxide (pGO) to facilitate combined chemotherapy in one system. In this study, nano-sized pGO-Pt/DOX ranged around 161.50 nm was fabricated and characterized using zeta-potential, AFM, TEM, Raman, UV-Vis, and FTIR analyses. The drug delivery efficacy of Pt was enhanced through the introduction of pGO, and the final weight ratio of DOX: Pt: pGO was optimized to 0.376: 0.376: 1. In vitro studies revealed that pGO-Pt/DOX nanoparticles could be effectively delivered into tumor cells, in which they induced prominent cell apoptosis and necrosis and exhibited higher growth inhibition than the single drug delivery system or free drugs. The pGO-Pt/DOX induced the most prominent cancer cell apoptosis and necrosis rate with 18.6%, which was observed almost 2 times higher than that of pGO-Pt or pGO-DOX groups. in the apoptosis and necrotic quadrants In vivo data confirmed that the pGO-Pt/DOX dual-drug delivery system attenuated the toxicity of Pt and DOX to normal organs compared to free drugs. The tumor inhibition data, histopathology observations, and immunohistochemical staining confirmed that the dual-drug delivery system presented a better anticancer effect than free drugs. These results clearly indicated that the pGO-Pt/DOX dual-drug delivery system provided the means for combination drug delivery in cancer treatment.

Intratissue topical medication is important for the treatment of cutaneous, mucosal or splanchnic diseases. However, penetrating surface barriers to providing adequate and controllable drug delivery while guaranteeing adhesion in bodily fluids remains challenging. Here, the predatory behavior of the blue-ringed octopus inspired us with a strategy to improve topical medication. For effective intratissue drug delivery, the active injection microneedles were prepared in a manner inspired by the teeth and venom secretion of blue-ringed octopus. With on demand release function guided by temperature-sensitive hydrophobic and shrinkage variations, these microneedles can supply adequate drug delivery at an early stage and then achieve the long-term release stage. Meanwhile, the bionic suction cups were developed to facilitate microneedles to stay firmly in place (>10 kilopascal) when wet. With wet bonding ability and multiple delivery mode, this microneedle patch achieved satisfactory efficacy, such as accelerating the ulcers’ healing speed or halting early tumor progression.

Bone substitute biomaterials, whose compositions and structures both play vital roles in bone defect healing, hold promising prospects in the clinical treatment of bone defects. Three-dimensional (3D) printed porous scaffolds incorporating osteoinductive components are considered as ideal bone grafts, because of the accurate control of structure parameters and the capacity to enhance bone tissue regeneration. Our previous studies demonstrated that nanoscale zeolitic imidazolate framework-8 (nanoZIF-8), a subclass of metal organic frameworks (MOFs), presented minimal cytotoxicity, inhibited bacterial activities, and promoted osteogenesis both in vitro and in vivo. However, the application of nanoZIF-8 in the 3D printed scaffold system remains unknown. In this study, nanoZIF-8 was incorporated into composite scaffolds composed of polycaprolactone (PCL) and dicalcium phosphate dihydrate (DCPD) via extrusion-based 3D printing technology. The results revealed that the composite scaffolds possessed increased mechanical strength and exhibited homogeneous structure with highly interconnected macropores. In vitro studies indicated that scaffolds showed biocompatibility to bone mesenchymal stem cells (BMSCs), significantly up-regulated the expression of osteogenesis-related genes and proteins, and facilitated the extracellular matrix mineralization. In vivo results showed that 3D printed porous scaffolds promoted new bone formation and enhanced micro-architecture at the critical defect sites (Φ10 mm) in rabbits, compared with the blank control group. Moreover, composite scaffolds significantly improved calvarial defect healing in comparison with scaffolds without nanoZIF-8 incorporation. In summary, nanoZIF-8 modified 3D printed porous composite scaffolds demonstrated great potential in the treatment of critical-sized bone defects, proving the effectiveness of MOF incorporation in 3D printed composite scaffolds to promote osteogenesis in the field of bone tissue engineering.