Engineering the surface of materials with desired multifunctionalities is an effective way to fight against multiple adverse factors during tissue repair process. Recently, metal-polyphenol networks (MPNs) have gained increasing attention because of their rapid and simple deposition process onto various substrates (silicon, quartz, gold and polypropylene sheets, etc.). However, the coating mechanism has not been clarified, and multifunctionalized MPNs remain unexplored. Herein, the flavonoid polyphenol procyanidin (PC) was selected to form PC-MPN coatings with Fe³⁺, and the effects of different assembly parameters, including pH, molar ratio between PC and Fe³⁺, and material priority during coating formation, were thoroughly evaluated. We found that the material priority (addition sequence of PC and Fe³⁺) had a great influence on the thickness of the formed PC-MPNs. Various surface techniques (e.g., ultraviolet–visible spectrophotometry, quartz crystal microbalance, X-ray photoelectron spectroscopy, atomic force microscopy, and scanning electron microscopy) were used to investigate the formation mechanism of PC-MPNs. Then PC-MPNs were further engineered with multifunctionalities (fastening cellular attachment in the early stage, promoting long-term cellular proliferation, antioxidation and antibacterial activity). We believe that these findings could further reveal the coating formation mechanism of MPNs and guide the future design of MPN coatings with multifunctionalities, thereby greatly broadening their application prospects, such as in sensors, environments, drug delivery, and tissue engineering. Graphical Abstract

Collagen, commonly used in tissue engineering, is widespread in various tissues. During bone tissue regeneration, collagen can stimulate the cellular response and determine the fate of cells. In this work, we integrated collagen type II with procyanidin (PC) onto an implant coating by applying a layer-by-layer technique to demonstrate that collagen and PC can participate in the construction of new biomaterials and serve as multifunctional components. The effects of PC/collagen multilayers on the viability of cocultured bone marrow mesenchymal stem cells (BMSCs) were analyzed by cell counting kit-8 analysis and phalloidin staining. The reactive oxygen species level of BMSCs was revealed through immunofluorescent staining and flow cytometry. Osteogenesis-related genes were detected, and in vivo experiment was performed to reveal the effect of newly designed material on the osteogenic differentiation of BMSCs. Our data demonstrated that in BMSCs PC/collagen multilayers accelerated the proliferation and osteogenic differentiation through Wnt/β-catenin signaling pathway and enhanced bone generation around the implant in the bone defect model of rabbit femurs. In summary, combination of collagen and PC provided a new sight for the research and development of implant materials or coatings in the future.

Stroke is a major public health issue, corresponding to the second cause of mortality and the first cause of severe disability. Ischemic stroke is the most common type of stroke, accounting for 87% of all strokes, where early detection and clinical intervention are well known to decrease its morbidity and mortality. However, the diagnosis of ischemic stroke has been limited to the late stages, and its therapeutic window is too narrow to provide rational and effective treatment. In addition, clinical thrombolytics suffer from a short half-life, inactivation, allergic reactions, and non-specific tissue targeting. Another problem is the limited ability of current neuroprotective agents to promote recovery of the ischemic brain tissue after stroke, which contributes to the progressive and irreversible nature of ischemic stroke and also the severity of the outcome. Fortunately, because of biomaterials’ inherent biochemical and biophysical properties, including biocompatibility, biodegradability, renewability, nontoxicity, long blood circulation time, and targeting ability. Utilization of them has been pursued as an innovative and promising strategy to tackle these challenges. In this review, special emphasis will be placed on the recent advances in the study of nanomaterials for the diagnosis and therapy of ischemic stroke. Meanwhile, nanomaterials provide much promise for neural tissue salvage and regeneration in brain ischemia, which is also highlighted.

Implantable catheters are susceptible to severe complications due to non-specific protein adhesion on their surfaces. Polyethylene glycol (PEG) coatings, the gold standard for resistance to non-specific protein adhesion, present a challenge in achieving high-density grafting, which significantly restricts their use as anti-biofouling coatings. Herein, we exploited the strong interaction between polyphenols (PCs) and polycations (K6-PEG) to graft PEG onto the surface of PC-Cu (A network of metal polyphenols composed of proanthocyanidins and metal copper ions, with expectation for the coating with excellent resistance to non-specific protein adhesion (PC-Cu@K6-PEG). The introduction of K6-PEG resulted in enhanced stability and modulus of PC-Cu, as well as a reduction in the surface adhesion energy and contact angle of PC-Cu. In contrast to previously reported PEG coatings, PC-Cu@K6-PEG exhibited a markedly elevated grafting density of PEG (4.06 chains/nm²), which was more than double the highest value previously reported (1.9 chains/nm²), due to the diffusing ability of K6-PEG throughout the PC-Cu networks. PC-Cu@K6-PEG displays robust resistance to a variety of proteins, microbials, and platelet attachment, thereby preventing thrombosis. The coating ability of PC-Cu onto diverse substrates, combined with the simple, straightforward and environmentally benign process of fabricating PC-Cu@K6-PEG, suggests that this strategy has significant potential for use in anti-biofouling surfaces.

Utilizing complementary bioactive peptides is a promising surface engineering strategy for bone regeneration on osteogenesis. In this study, we designed block peptides, (Lysine)₆-capped RGD (K₆-(linker-RGD)₃) and OGP (K₆-linker-(YGFGG)₂), which were mildly grafted onto PC/Fe-MPNs through supramolecular interactions between K₆ and PC residues on the MPNs surface to form a dual peptide coating, named PC/Fe@K₆-RGD/OGP. The properties of the block peptides coating, including mechanics, hydrophilicity, chemical composition, etc., were detailly characterized by various techniques (ellipsometry, quartz crystal microbalance, X-ray photoelectron spectroscopy, water contact angle, scanning electronic microscopy and atomic force microscopy). Importantly, the RGD/OGP ratio can be well adjusted, which allowed optimizing the RGD/OGP ratio to endow significantly enhanced osteogenic activity of MC3T3-E1 cells through the Wnt/β-catenin pathway, while also promoting cell adhesion, immune regulation, inhibiting osteoclast differentiation and oxidative stress reduction. In vivo, the optimized RGD/OGP coatings promoted bone regeneration and osseointegration around implants in rats with bone defects. In conclusion, rationally designed PC/Fe@K₆-RGD/OGP coating integrated RGD and OGP bioactivities, providing a convenient approach to enhance bioinert implant surfaces for bone regeneration.