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It is urgent to develop biocompatible and high-efficiency antimicrobial agents since microbial infections have always posed serious challenges to human health. Herein, through the marriage of facially amphiphilic skeletons and cationic dendrimers, high-density positively charged dendrimers D-CA

A self-healing hydrogel with a dual network was prepared through the host–guest recognition of acrylate γ-cyclodextrins with tetraphenylethylenes, and the fluorescence of hydrogel was enhanced in the presence of α-amylase.

Shape memory polymers (SMPs) are a type of programmable materials capable of transforming their shapes in a pre-programmed way upon the application of an external stimulus. These materials have been tested for various potential applications particularly in the biomedical field for polymers with general and specific requirements. This review focuses on the recent advances in biomedical applications, including self-tightening sutures, pressure bandages, self-expansion stents, tissue engineering scaffolds, artificial muscles, drug delivery, and orthodontic archwires, after a brief description of the concepts, classifications, programming procedures, and material requirements of SMPs.

The early stages of progressive degeneration of cartilage in articular joints are a hallmark of osteoarthritis. Healthy cartilage is lubricated by brush-like cartilage-binding nanofibres with a hyaluronan backbone and two key side chains (lubricin and lipid). Here, we show that hyaluronan backbones grafted with lubricin-like sulfonate-rich polymers or with lipid-like phosphocholine-rich polymers together enhance cartilage regeneration in a rat model of early osteoarthritis. These biomimetic brush-like nanofibres show a high affinity for cartilage proteins, form a lubrication layer on the cartilage surface and efficiently lubricate damaged human cartilage, lowering its friction coefficient to the low levels typical of native cartilage. Intra-articular injection of the two types of nanofibre into rats with surgically induced osteoarthritic joints led to cartilage regeneration and to the abrogation of osteoarthritis within 8 weeks. Biocompatible injectable lubricants that facilitate cartilage regeneration may offer a translational strategy for the treatment of early osteoarthritis. Brush-like biopolymers mimicking the lubrication properties of natural cartilage-binding complexes in articular joints enhance cartilage regeneration in a rat model of early osteoarthritis.

Digital light processing (DLP) 3D printing has been utilized to fabricate controlled porous β-tricalcium phosphate (β-TCP) scaffolds, which promote cell adhesion and angiogenesis during bone regeneration. However, the current limitation of DLP 3D printing for the fabrication of β-TCP scaffold is how to prepare a low viscosity ceramic slurry and remove the toxicity of residual non-polymerized slurry. The present study has developed a low viscosity ceramic slurry system by mixing β-TCP with photosensitive acrylate resin, and the viscosity of slurry is about 3 Pa s and the solid content of β-TCP can be as high as 60 wt%. After optimizing the ratio of slurry, printing, degreasing and sintering processes, the maximum compressive strength of the DLP printed scaffolds reaches up to 9.89 MPa, while the porosity keeps ca. 40%. According to the proliferation of cells, it confirms the preserved biocompatibility of DLP-fabricated β-TCP scaffolds. These porous scaffolds made by DLP 3D printing technology is of great significance for bone regeneration, and will also help to expand the application of DLP technology in biomedical field.

Zinc ions (Zn2+) play a critical role in the regulation of zinc enzymes and cell metabolism. However, previous Zn2+ delivery methods are usually based on pH-responsive zinc coordination complexes, which are difficult for the precise control of Zn2+ release at desired locations. To tackle this challenge, we herein developed a photo-triggered Zn2+ release system based on HBTH–Zn–TAT nanoparticles (NPs) with 2-(2-hydroxyphenyl)-benzothiazolines (HBTH) as the Zn2+ ligand, DSPE–PEG/DSPE–PEG–Mal polymers as the matrix and TAT peptide as the cell penetrating ligand. HBTH–Zn–TAT NPs can quickly release Zn2+ under white light irradiation and efficiently regulate extra- and intracellular zinc enzyme activities, such as carbonic anhydrase, caspase-3 and protein phosphatase type 2A (PP2A). Based on the advantages of the photo-triggered release of Zn2+ with a high spatiotemporal resolution, HBTH–Zn–TAT NPs are promising for the regulation of zinc enzymes and corresponding bioactivities.

The stimuli-responsive polymers with upper critical solution temperatures (UCST) are highly attractive for drug delivery applications. However, the phase transition process of UCST polymer is usually characterized by turbidity measurement and electron microscopy, which are significantly restricted by low sensitivity and static observation. In contrary, the fluorescence technique has significant advantages in terms of high sensitivity, easy operation, and dynamic observation. However, the conventional fluorophores suffer from the drawbacks of aggregation-caused quenching (ACQ) after being encapsulated by UCST polymers, which are not suitable for direct visualization of the phase transition process. To tackle this challenge, we herein developed a series of UCST polymers based on polyacrylamides decorated with bile acid and aggregation-induced emission (AIE)-active tetraphenylethene (TPE) groups, which can be used for direct fluorescence monitoring of the phase transition process. Moreover, the AIE-active UCST polymers can serve as drug carriers, which can not only monitor the drug release process under thermal stimuli, but also verify the drug release by fluorescence recovery after thermal stimuli. It is expected that the AIE-active UCST polymers with self-monitoring ability are promising for biomedical applications.

Facing the challenges posed by bacterial infection, the real-time detection of bacterial infection combined with antibacterial functions is urgently needed. Herein, we prepare thermo- and pH-responsive poly(vinyl alcohol) derivatives (PVA–TPE) bearing aggregation-induced emission luminogens of tetraphenylethene (TPE) and quaternary ammonium moieties through a facile one-pot quaternization with a tertiary amine method. Intrinsic fluorescence from TPE moieties and antibacterial functions from quaternary ammonium units can efficiently integrate the functions of “monitoring and killing of bacteria”. It is found that PVA–TPE can selectively image and kill Gram-positive bacteria at pH 7.4, while it switched to display enhanced broad-spectrum antimicrobial activity against both Gram-negative and -positive bacteria in an acidic environment (pH 5.5). Moreover, PVA–TPE exhibits low cytotoxicity on mammalian cells of L929, HepG2 and red blood cells. Furthermore, in vivo evaluations further confirmed that PVA–TPE has excellent antibacterial efficacy with no tissue damage. This study represents the first example of a pH-switchable integrated system for “monitoring and killing of bacteria” constructed through a facile one-pot quaternization method.

Developing nanocomposite hydrogel with multi-functions including adjustable mechanical property, tissue-adhesion, and blood coagulation property to accelerate wound healing is highly desirable in surgical application. Here a macroporous adhesive nano-enabled hydrogel constructed from gelatin methacryloyl stabilized air-in-water emulsions incorporated with dopamine-grafted-gelatin (GelDA) and Laponite nanoclay is reported. The hydrogel exhibits interconnected macroporous structure. The physical/chemical cross-linked network formed among the various components contributes to the good mechanical strength of hydrogel, which could be further regulated by adjusting the concentration of Laponite nanoclay. Furthermore, the nanocomposite macroporous hydrogel is endowed with self-healing properties and tissue adhesion by the intermolecular hydrogen bonds, ionic interactions among Laponite nanoclay and polymers, as well as the catechol functional groups. The in vitro studies demonstrate that the macroporous hydrogel has good biocompatibility and could significantly reduce blood clotting time, which is expected to be applied for the rapid sealing and hemostasis of bleeding wounds.

Corneal transplantation is the widely accepted treatment to restore sight for corneal blindness. To date, because of the global donor cornea shortage, there is a need for alternatives to human donor corneas. Biocompatible collagen is an excellent candidate material for corneal repair in the view of biomimetics. Herein a class of polyrotaxane multiple aldehyde (PRA) cross-linkers based on the host–guest supramolecules of α-cyclodextrins and poly(ethylene glycol) is prepared to cross-link with collagen to fabricate materials for corneal repair. Aldehyde groups from rotaxanes and α-cyclodextrin units can synergistically improve the mechanical and optical properties of PRA cross-linked collagen membranes (Col-PRAs). Compared with counterparts cross-linked by traditional a cross-linker of 1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide and N-hydroxy-succinimide, Col-PRAs have better mechanical properties, especially suture resistance as well as optical properties. In vivo lamellar keratoplasty results indicat...

Cell-material interactions are important to tissue engineering. Inspired by the natural topographic structures on the extracellular matrix, a growing number of studies have integrated engineering topography into investigations of cell behavior on biomaterials. Engineering topography has a significant influence on cell behaviors. These cell-topography interactions play an important role in regenerative medicine and tissue engineering. Similarly, cell-topography interactions are important to corneal reconstruction and regeneration. In this review, we primarily summarized the effects of topographic cues on the behaviors of corneal cells, including cell morphology, adhesion, migration, and proliferation. Furthermore, the integration of engineering surface topography into corneal tissue engineering was also discussed., Graphical abstract Image 1, Highlights • This article aims to provide insight into the potential applications of topography on corneal reconstruction and regeneration. • Discussed the relation between surface topography and corneal repair. • Reviewed the effect of topographic cues on corneal cell behaviors. • Reviewed the applications of topographic cues in corneal tissue engineering. • Discussed the underlying mechanism of the topographic effect on cell behaviors.

Alternating polyurethanes (PUs) of poly(ethylene glycol) (PEG) and bile acids were synthesized through a single step condensation and then conjugated with a tetraphenylethene (TPE) derivative, a ty...

Collagen is a promising material for corneal tissue engineering. The surface topography of collagen is critical for cornea reconstruction and regeneration. Herein, we fabricated collagen films with microgrooved surface to investigate the effect of collagen film topography on corneal cell migration and antifibrosis. We found that the patterned films with microscale grooves could greatly affect the orientation, proliferation, migration, and gene expression of rabbit corneal epithelial cells and keratocytes. Compared with the natural cornea, the optimized collagen films with microgroove pattern show similar swelling performance, optical clarity, and biodegradability, which could efficiently promote the epithelial cell migration, accelerate wound healing process, and inhibit the fibrosis of keratocytes. These results suggest that collagen films with microgroove pattern are promising in corneal tissue engineering.

Self-healing is one of the most fundamental properties of living tissues that allows them to withstand repeated damage. Self-healing hydrogels, which can spontaneously recover themselves after being ruptured, result in enhanced lifetimes for materials and open up a fascinating direction in materials science. Host-guest interactions have been widely used in the construction of self-healing hydrogels. We have emphasized the preparation and biomedical applications of self-healing hydrogels assembled by host-guest interactions, focusing on hosts of cyclodextrins and cucurbit[n]urils with various guests and tailored structures. The applications of self-healing hydrogels in biomedical fields such as drug delivery, encapsulation of cells and tissue engineering and 3D printing as well as interfacial adhesion were also summarized. At the end of this review, we propose the current challenges and future perspectives in this developing area.

A supramolecular hybrid hydrogel displaying a wide array of dynamic physical properties along with enhanced in vivo stem cell retention has been developed. The key strategy is facilely polymerizing bioactive gelatin methacrylate (GelMA) with 2-(2-methoxyethoxy)ethyl methacrylate (MEO2MA) and 2-(3-(6-methyl-4-oxo-1,4-dihydropyrimidin-2-yl)ureido)ethyl methacrylate (UPyMA) to generate one hybrid branched copolymer. Rapid gelation occurs upon increasing the temperature above the lower critical solution temperature (LCST) of this supramolecular copolymer, where PMEO2MA segments dehydrate and assemble into clusters, providing a hydrophobic microenvironment facilitating UPy dimerization to connect polymer chains, thus forming quadruple hydrogen bond reinforced crosslinking networks. The biodegradable, self-healing, thermo-reversible and injectable properties of the supramolecular hydrogel are finely tunable by changing the hydrogel formulation. Mesenchymal stem cells encapsulated in the hydrogel show high viability and proliferation. The subcutaneous study shows that the stem cells delivered within the in situ formed hydrogel are well protected from mechanical damage and have significantly enhanced in vivo cell retention for three weeks. These results suggest that the dynamic supramolecular hydrogel can be utilized to regulate stem cells for tissue regeneration applications.

Tuning the fluorescence of aggregation-induced emission (AIE)-based materials in a reversible way is essential and a requisite for their applications. The multiple host-guest interactions of polypseudorotaxanes (PPRs) could alter the aggregation state of hydrophobic AIE-based polymeric materials and consequently switch the fluorescence. Herein, tetraphenylethylene (TPE) as a typical AIE molecule has been incorporated into the main chains of the guest polyurethane via a step condensation between poly(ethylene glycol) (PEG)-based dicarbonate and TPE-diamine along with the cleavable disulfide bonds. γ-Cyclodextrins (γ-CDs) can selectively recognize the TPE units at the polyurethane chains to afford a PPR. Hydrophilic PEG segments and γ-CD molecules in the PPR could promote the disaggregation of TPE units, suppressing the fluorescence emission of TPE. To restore the aggregated state and fluorescence of TPE units, tris(2-carboxyethyl)phosphine (TCEP) and α-amylase are sequentially introduced to cleave the disulfide bonds and cut α-1,4 glycosidic bonds of γ-CD, reactivating the AIE behavior of PPR tandemly and accomplishing the reversible cycle of tuning the fluorescence of TPE. The present study provides a tandem way to switch the AIE behavior of polymeric materials reversibly.

With the emergence of drug-resistant bacteria and the formation of biofilms by bacteria and fungi, microbial infections gradually threaten global health. Natural antimicrobial peptides (AMPs) have low susceptibility for developing resistance due to the membrane targeted mechanism, but instability and high manufacturing cost limit their applications in clinic. Bile acids, a group of steroids in the human body, with high stability, biocompatibility, and inherent facial amphiphilic structure similar to the characteristics of AMPs, have been applied to the biological field, such as drug delivery systems, self-healing hydrogels, antimicrobials, and so on. In this review, we mainly focus on the different classes of bile acid-based antimicrobials in recent years. Various designs and methods for the preparation of unimolecular antimicrobials with bile acid skeletons are first introduced, including coupling of primary amine, quaternary ammonium, and amino acid units with bile acid skeletons. Some representative oligomeric antimicrobials, including dimers of bile acids, are summarized. Finally, macromolecular antimicrobials bearing some positive charges at the main chain or side chain and interaction mechanisms of these bile acid-based antimicrobials are discussed.

For the design of shape memory polymers with potential biomedical applications, we synthesized methacrylate-based monomers bearing biological compounds such as cholic acid and cinnamic acid in addition to oligo(ethylene glycol) as pendant groups and opted to use a simple radical polymerization method for the preparation of the copolymers. The glass transition temperatures of these polymers are broad and tunable and can thus accommodate dual and triple shape memory behaviors. The fixity ratios of dual and triple shape memory are all above 91%. The recovery ratio of dual shape memory is 89.5%, whereas the two recovery ratios of triple shape memory are 53.2 and 81.5%, respectively. To further improve the shape memory properties, a cinnamic acid-based methacrylate monomer was incorporated into the copolymers to enable a photo-cross-linking of the terpolymer. After irradiation, the fixity ratios remain high, whereas the recovery ratios of dual and triple shape memories are much improved. The terpolymers after light irradiation even show quadruple shape memory property. Different irradiation times were tested to optimize the shape memory effects. The recovery ratio of dual shape memory of such terpolymers can reach as high as 98.6%, whereas the recovery ratios of triple and quadruple shape memories are improved to the range of 75.3-99.1%.

Electro-active conducting hydrogels have shown promising applications in promoting soft tissue regeneration. However, achieving good conductive performance while simultaneously imparting macroporous structures to these hydrogels still remains challenging. In this study, we report the development of multifunctional conductive macroporous nanocomposite hydrogels (MNHs) prepared by an air-in-water emulsion template that is stabilized by colloidal hybrids of carbon nanotubes (CNTs) and gelatin methacryloyl. The MNH hydrogels demonstrated tunable pore size, electrical conductivity and mechanical properties with various CNT concentrations in the crosslinking matrices. An in vitro cell assay showed that the MNH hydrogels could promote the spreading and differentiation of NE-4C neural stem cells. Furthermore, sustainable release of antimicrobial peptides (AMPs) from the MNH hydrogel can be achieved and the released AMPs maintained high S. aureus killing activity. An in vivo evaluation of the MNH hydrogel using a murine dorsal skin model further showed that the conductive MNH hydrogel loaded with AMPs demonstrated appealing antimicrobial and wound healing performance in two weeks.

As the main component of the natural cornea, collagen (COL) has been widely applied to the construction of corneal repair materials. However, the applications of collagen are limited due to its poor mechanical properties. Cellulose nanocrystals (CNCs) possess excellent mechanical properties, optical transparency and good biocompatibility. Therefore, in this study, we attempted to introduce cellulose nanocrystals into collagen-based films to obtain corneal repair materials with a high strength. CNCs were incorporated at 1, 3, 5, 7 and 10 wt%. The physical properties of these composite films were characterized, and in vitro cell-based analyses were also performed. The COL/CNC films possessed better mechanic properties, and the introduction of CNCs did not affect the water content and light transmittance. The COL/CNC films demonstrated good biocompatibility toward rabbit corneal epithelial cells and keratocytes in vitro. Moreover, the collagen films with appropriate ration of CNCs effectively induced the migration of corneal epithelial cells and inhibited the myofibroblast differentiation of keratocytes. A collagen film with 7 wt% CNCs displayed the best combination of physical properties and biological performance in vitro among all the films. This study describes a nonchemical cross-linking method to enhance the mechanical properties of collagen for use in corneal repair materials and highlights potential application in corneal tissue engineering.

Self-healing hydrogels can heal themselves on the damaged sites, which opens up a fascinating way for enhancing lifetimes of materials. Polypeptide/poly(amino acid) is a class of polymers in which natural amino acid monomers or derivatives are linked by amide bonds with a stable and similar secondary structure as natural proteins (α-helix or β-fold). They have the advantages of nontoxicity, biodegradability, and low immunogenicity as well as easy modification. All these properties make polypeptides extremely suitable for the preparation of self-healing hydrogels for biomedical applications. In this review, we mainly focus on the progress in the fabrication strategies of polypeptide-based self-healing hydrogels and their biomedical applications in the recent 5 years. Various crosslinking methods for the preparation of polypeptide-based self-healing hydrogels are first introduced, including host-guest interactions, hydrogen bonding, electrostatic interactions, supramolecular self-assembly of β-sheets, and reversible covalent bonds of imine and hydrazone as well as molecular multi-interactions. Some representative biomedical applications of these self-healing hydrogels such as delivery system, tissue engineering, 3D-bioprinting, antibacterial and wound healing as well as bioadhesion and hemostasis are also summarized. Current challenges and perspectives in future for these "smart" hydrogels are proposed at the end . STATEMENT OF SIGNIFICANCE: Polypeptides with the advantages of nontoxicity, biodegradability, hydrophilicity and low immunogenicity, are extremely suitable for the preparation of self-healing hydrogels in biomedical applications. Recently, the researches of polypeptide-based self-healing hydrogel have drawn the great attentions for scientists and engineers. A review to summarize the recent progress in design and biomedical applications of these polypeptide-based self-healing hydrogels is highly needed. In this review, we mainly focus on the progress in fabrication strategies of polypeptide-based self-healing hydrogels and biomedical applications in recent five years and aim to draw the increased attention to the importance of these "smart" hydrogels, facilitating the advances in biomedical applications. We believe this work would draw interest from readers of Acta Biomaterialia.

Immediate hemorrhage control and wound closure play important roles in soft-tissue wound management. Developing adaptable sealant dressings with multi-functions to accelerate wound healing is highly demanded but remains challenging. In this study, we report a macroporous nano-enabled sealant based on gelatin methacryloyl stabilized air-in-water emulsions combined with Laponite nanoclays and poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS). The sealant demonstrates tunable pore size, robust mechanical properties, conductivity and wet-adhesiveness. Imparting macroporous structures and nanoclays, the biocompatible sealant could well support cell adhesion and proliferation, and reveal promising in vitro blood clotting ability as well as haemostatic performance in a rat liver lethal hemorrhage model in vivo. Furthermore, the results from a full-thickness skin defect model clearly demonstrate this conductive macroporous nano-enabled sealant could significantly promote granular tissue growth and collagen deposition thus accelerated wound healing process.

A “biowheel-axle” assembly of polyrotaxanes of β-cyclodextrin (β-CD) threaded onto bile acid moieties linked by a poly(ethylene glycol) (PEG) spacer of tunable length was prepared through an “inclusion polymerization” approach. The bile acid-diamine derivatives were allowed to first form inclusion complexes with β-CD and then polymerized with PEG-dicarbonate, followed by end-capping with a stopper of monoamino-β-CD, resulting in “biowheels” of β-CD with PEGylated bile acids as the axle in tandem. All steps were performed without the use of catalysts. The complexation between β-CD and bile acid units of the polymer chain was confirmed by the 2D NOESY NMR technique and powder X-ray diffraction, showing 85% of bile acid units entered the cavity of β-CD. The change of PEG spacer length from 45 to 6 ethylene glycol units led to a flexible–rigid conformation transition of the polyrotaxanes, supported by the random and straight orientation of the “biowheels” shown by scanning tunneling microscopy images. The con...

Poly(vinyl alcohol) (PVA) is a cytocompatible synthetic polymer and has been commonly used to prepare hydrogels. Bile acids and β-cyclodextrin are both natural compounds and they form stable host-guest inclusion complexes. They are attached covalently onto a low molecular weight PVA separately. Self-healing hydrogels can be easily formed by mixing the aqueous solutions of these PVA based polymers. The mechanical properties of the hydrogels can be tuned by varying the molar fractions of bile acid units on PVA. The dynamic inclusion complexation of the host-guest pair of the hydrogel allows the self-healing rapidly under ambient atmosphere and their mechanical properties could recover their original values in 1 min after incision. These PVA based polymers exhibited the good cytocompatibility and high hemocompatibility as shown by their biological evaluations. The use of natural compounds for host-guest interaction make such gels especially convenient to use as biomaterials, an advantage over conventional hydrogels prepared through freeze-thaw method.

A series of novel bacterial cellulose/C60 (BCC60) composites was prepared using a original dehydration-rehydration method. The composites were characterized to demonstrate their potential in multifunctional wound dressings for skin cancer treatment using photodynamic therapy. Raman spectroscopy revealed that the C60 nanoparticles were successfully incorporated into the bacterial cellulose (BC) network. Scanning electron microscopy was used to examine the morphology and distribution of the C60 particles as photosensitizers in the bacterial cellulose network, and the C60 particles were uniformly distributed in the hyperfine three-dimensional BC network with diameters less than 100 nm. Reactive oxygen species (ROS) measurements indicated that the BCC60 composites possessed a high ROS generation ability when exposed to light. The antibacterial assessment of the BCC60 composites revealed their ability to inhibit the growth of E. coli and S. aureus and their relationship with light irradiation. In vitro cell experiments also confirmed that the BCC60 composites had low cytotoxicity in the dark, while they exhibited significant cancer cell damage activity under visible light.

The use of natural compounds to construct reversible networks is an attractive strategy in biomaterials design. Our design is based on a host–guest pair of natural compounds β-cyclodextrin and cholic acid through the use of a cholic acid dimer tethered with a poly(ethylene glycol) spacer, which subsequently served as a guest cross-linker to afford a hydrogel with copolymers bearing β-cyclodextrin pendants. The hydrogel after incision self-heals rapidly under ambient atmosphere as observed and confirmed by rheological measurements. To endow the hydrogels with reversibility and responsiveness, the addition of a CO2-switchable guest of benzimidazole followed by alternating treatments with CO2 and N2 leads to a reversible sol–gel transition due to the dynamic complexation between the cholic acid and β-cyclodextrin units. The CO2 responsiveness and the natural origin of the constituents make these self-healing hydrogels attractive as smart biomaterials.

Two-way reversible shape memory polymers (2W-SMPs) are highly desirable for many applications. We report for the first time the use of random copolymers with cocrystallizable monomeric units for the preparation of such polymer networks. Homopolymers and random copolymers of e-caprolactone and ω-pentadecalactone were designed and made by ring-opening polymerization with Candida antarctica lipase B as catalyst. The melting temperatures of these prepolymers may be adjusted by the use of various molar ratios of the comonomers. Upon thiol–ene cross-linking, the polymer network exhibited two-way reversible shape memory effects under both stress-free and stress conditions. The actuation temperature (TA) of the 2W-SMP under stress-free condition can be tuned in a broad range using a selected mixture of prepolymers followed by photo-cross-linking with a multifunctional cross-linker. Increasing the initial stretching stress amplitude led to an increased absolute strain change under both stress-free and stress condi...

Betulin is a natural triterpene compound with anticarcinogen and antiviral activities. It is conjugated with methacrylate and then copolymerized with a galactose-bearing comonomer by RAFT polymerization to yield both random and block copolymers. These glycopolymers are designed to possess similar molecular weights and monomer compositions for easy comparison. They self-assembled into micelles, as shown by dynamic light scattering (DLS) and transmission electron microscopy. The smaller micelles formed by the random copolymers facilitated the encapsulation of Nile Red and released more of this hydrophobic model compound (46% in 4 days versus 32% released from the block copolymers). These glycopolymers interacted with lectins, such as RCA120, as studied by turbidity assay and DLS. The block copolymers formed larger aggregates and clustered faster than the random copolymers. The betulin-based glycopolymers may serve as biocompatible multifunctional biomaterials and carriers for use in targeted release of drugs.

Acrylamide derivatives of bile acids are chosen as a hydrophobic comonomer to copolymerize with acrylamide via reversible addition and fragmentation chain transfer (RAFT) polymerization to afford a series of copolymers of P(AAm-co-CAA). These copolymers exhibit a sharp and reversible insoluble–soluble transition in water upon heating to a mixing temperature (Tmix) related to the upper critical solution temperature (UCST). Tmix of these copolymers can be conveniently tuned to a practical temperature range, around 37 °C for biomedical applications. Tmix rises with increasing molar fraction of the bile acid-based acrylamide and increasing concentration of the aqueous solution of the copolymers. The addition of a natural host molecule β-cyclodextrin lowered the Tmix. The insoluble–soluble transition of the copolymers was also evidenced by dynamic light scattering and transmission electron microscopy. The biocompatible nature of the bile acids and β-cyclodextrins may make these copolymers potentially useful fo...

Hypochlorous acid (HOCl) and peroxynitrite (ONOO−) are two of the most important reactive species and associated with various diseases in various physiological and pathological processes. Nonetheless, many of their roles are still vague due to the shortage of methods for simultaneously detecting HOCl and ONOO−. Herein, three simple yet useful fluorogenic probes, LG-1, LG-2 and LG-3, have been fabricated with facile synthesis route and used to monitor the coexistence of HOCl and ONOO− as AND-based logic gate fluorescent probe firstly. LG-1 and LG-2, which consists of 1,3-oxathiolane group and boronate group respectively, were designed to verify the capacity of monitoring HOCl and ONOO− without interference from each other. The result showed that these two groups are perfect reaction sites of detecting HOCl and ONOO− respectively via specific analyte-induced reactions. Hence, LG-3, which is attached by these two groups to suppress the fluorophore core, can response to HOCl and ONOO− simultaneously without mutual interference and generate the significant time-dependent fluorescence enhancement. By investigating the absorption and fluorescence properties of LG-3 towards HOCl and ONOO− individually and collectively, the result confirmed clearly that LG-3 has the capacity of monitoring the coexistence of HOCl and ONOO−, which could act as a two-input AND-based logic gate fluorescent probe.

Supramolecular and dynamic covalent crosslinking (DCC) hydrogels not only display unique physicochemical properties that can mimic the dynamic extracellular matrix (ECM), but also have the capabilities of shear-thinning, self-healing and even shape memorizing. Specifically, through the breaking and reforming of the reversible linkage, cells can be readily encapsulated in the matrix and can well maintain their differentiation potentials. The dynamic shear-thinning and self-healing hydrogels can also be explored as cell-compatible bio-inks for the design of complex multicellular structures. These distinctive properties of dynamic hydrogels have attracted increasing interests in cell retention as well as cartilage tissue engineering. The biophysical and biochemical cues of hydrogel matrices have significant effects on cell fate. The studies on the relationship of cell response and the critical properties of hydrogels, such as mechanical strength, elasticity, ligand chemistry and degradation, are helpful in advancing dynamic hydrogels for cell retention and delivery. In this review, we highlight the most recent progress in the gelation strategies of biomedical supramolecular and DCC hydrogels and then focus on their applications for enhancing cell retention and cartilage/osteochondral regeneration. Furthermore, the challenges and future perspectives of supramolecular and DCC hydrogels in cell retention and cartilage regeneration are also discussed.

Although antimicrobial titanium implants can prevent biomaterial-associated infection (BAI) in orthopedics, they display cytotoxicity and delayed osseointegration. Therefore, versatile implants are desirable for simultaneously inhibiting BAI and promoting osseointegration, especially "statically-versatile" ones with nonessential external stimulations for facilitating applications. Herein, we develop a "statically-versatile" titanium implant by immobilizing an innovative fusion peptide (FP) containing HHC36 antimicrobial sequence and QK angiogenic sequence via sodium borohydride reduction promoted Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC-SB), which shows higher immobilization efficiency than traditional CuAAC with sodium ascorbate reduction (CuAAC-SA). The FP-engineered implant exhibits over 96.8% antimicrobial activity against four types of clinical bacteria (S. aureus, E. coli, P. aeruginosa and methicillin-resistant S. aureus), being stronger than that modified with mixed peptides. This can be mechanistically attributed to the larger bacterial accessible surface area of HHC36 sequence. Notably, the implant can simultaneously enhance cellular proliferation, up-regulate expressions of angiogenesis-related genes/proteins (VEGF and VEGFR-2) of HUVECs and osteogenesis-related genes/proteins (ALP, COL-1, RUNX-2, OPN and OCN) of hBMSCs. In vivo assay with infection and non-infection bone-defect model reveals that the FP-engineered implant can kill 99.63% of S. aureus, and simultaneously promote vascularization and osseointegration. It is believed that this study presents an excellent strategy for developing "statically-versatile" orthopedic implants.

The future of manufacturing applications in three-dimensional (3D) printing depends on the improvement and the development of materials suitable for 3D printing technology. This study aims to develop an applicable and convenient protocol for light-curing resin used in 3D industry, which could enhance antibacterial and mechanical properties of polymethyl methacrylate (PMMA) resin through the combination of nano-fillers of surface modified titanium dioxide (TiO2) and micro-fillers of polyetheretherketone (PEEK). PMMA-based composite resins with various additions of TiO2 and PEEK were prepared and submitted to characterizations including mechanical properties, distribution of the fillers (TiO2 or/and PEEK) on the fractured surface, cytotoxicity, antibacterial activity, and blood compatibility assessment. These results indicated that the reinforced composite resins of PMMA (TiO2-1%-PEEK-1%) possessed the most optimized properties compared to the other groups. In addition, we found the addition of 1% of TiO2 would be an effective amount to enhance both mechanical and antibacterial properties for PMMA composite resin. Furthermore, the model printed by PMMA (TiO2-1%-PEEK-1%) composite resin showed a smooth surface and a precise resolution, indicating this functional dental restoration material would be a suitable light-curing resin in 3D industry.

Polymeric nano-carriers are considered as promising tools in biomedical applications due to multiple attractive characteristics including their low toxicity, high loading capacity, controlled drug release capabilities, and highly tunable chemical properties. Here, a series of pH-sensitive star-shaped copolymers, Ad-P[(EMA-co-MAA)-b-PPEGMA]4, was prepared via electron transfer atom radical polymerization (ARGETE ATRP) and selective hydrolysis. These star-shaped copolymers can be self-assembled into micelles (Dh = 150&ndash, 160 nm) and their critical micelle concentrations (CMC) were estimated to be 3.9&ndash, 5.0 mg/L. The pH-sensitiveness of the micelles was evidenced by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The maximal paclitaxel (PTX) loading efficiency (DLC) and entrapment efficiency (EE) were 18.9% and 36%, respectively. In vitro release studies revealed that about 19% of the PTX released at an acidic condition of pH 1.2 over 70 h, whereas more than 70% was released within the same time interval at pH 6.8. In vitro cytotoxicity suggested that the low cytotoxicity of the blank micelles, while the PTX-loaded micelles providing the cytotoxicity close to that of free PTX. These results indicated that this novel pH-sensitive nano-carriers have great potential applications for oral drug-controlled release.

One of the most famous anticancer drugs, paclitaxel (PTX), has often been used in drug controlled-release studies. The polymers derived from bio-compound bile acids and degradable poly(&epsilon, caprolactone) (PCL) form a reservoir and have been used as a drug delivery system with great advantages. Herein, we grafted poly(N,N-diethylaminoethyl methacrylate) and poly(poly(ethylene glycol) methyl ether methacrylate) into the bile acid-derived three-armed macroinitiator CA-(PCL)3, resulting in the amphiphilic block copolymers CA-(PCL-b-PDEAEMA-b-PPEGMA)3. These pH-responsive three-armed block copolymers self-assembled into micelles in aqueous solution and PTX was encapsulated into the micellar core to form PTX-loaded micelles with a drug loading of 29.92 wt %. The micelles were stable in PBS at pH 7.4 and showed a pH-triggered release behavior of PTX under acidic environments, in which 55% of PTX was released at pH 5.0 in 80 h. These cholic acid-based functionalized three-armed block polymers present good biocompatibility, showing great potential for drug controlled-release.