Search

Highly cross-linked polyethylene (XLPE) is a major advance in total hip arthroplasty (THA), as it suffers from less wear and thus is associated with lower revision rates than standard ultra-high molecular weight polyethylene. Early failures are reported rarely, and associated with specific design or manufacturing issues. We report a case requiring early revision due to adverse reaction to polyethylene particles. Investigations identified insufficient irradiation as the most probable cause of failure. Here are reported the features of a clinical case with determination of the material properties of the retrieved XLPE liner and establishment of the appropriate calibration curves as reference. Periprosthetic joint infection could be ruled out with appropriate sampling as cause for the inflammatory periarticular tumour. Histology identified a massive macrophagic reaction to micrometric polyethylene particles. No component malposition was present, nor any third-body wear. The trans-vinylene index (TVI) indicated insufficient and potentially detrimental irradiation of the polyethylene, while gel content, crystallinity, melting temperature and oxidation index remained within expected ranges. Histologically proven failure of a XLPE THA liner was identifiable despite correct implantation of the components. The cause of failure most probably was an inadequate irradiation, as indicated by determination of the TVI. This case underscores the importance of histologic workup even in aseptic revisions, and of detailed analysis of retrievals. The calibration curves provided are essential for analysis of other retrievals.

3D culture of cells in designer biomaterial matrices provides a biomimetic cellular microenvironment and can yield critical insights into cellular behaviours not available from conventional 2D cultures. Hydrogels with dynamic properties, achieved by incorporating either degradable structural components or reversible dynamic crosslinks, enable efficient cell adaptation of the matrix and support associated cellular functions. Herein we demonstrate that given similar equilibrium binding constants, hydrogels containing dynamic crosslinks with a large dissociation rate constant enable cell force-induced network reorganization, which results in rapid stellate spreading, assembly, mechanosensing, and differentiation of encapsulated stem cells when compared to similar hydrogels containing dynamic crosslinks with a low dissociation rate constant. Furthermore, the static and precise conjugation of cell adhesive ligands to the hydrogel subnetwork connected by such fast-dissociating crosslinks is also required for ultra-rapid stellate spreading (within 18 h post-encapsulation) and enhanced mechanosensing of stem cells in 3D. This work reveals the correlation between microscopic cell behaviours and the molecular level binding kinetics in hydrogel networks. Our findings provide valuable guidance to the design and evaluation of supramolecular biomaterials with cell-adaptable properties for studying cells in 3D cultures., 3D culture systems can provide critical insights into cellular behaviour. Here, the authors study the binding timescale of dynamic crosslinks and the conjugation stability of cell-adhesive ligands in cell–hydrogel network interactions to evaluate the impact on stem cell behaviour, mechanosensing and differentiation.

The detection of oxygen (O2) by optical sensors is of growing importance, for example, in biology, life science, environmental science, and aerodynamics, where the composition of gases is crucial for many applications. Purely organic optical O2 sensors are very attractive for monitoring food deterioration, biosensing, and biomonitoring, as they can provide continuous, reversible, and nondestructive O2 sensing. However, purely organic optical reversible O2 sensors that can work with a broad O2 concentration range and that have robust reversibility are yet to be realized. We hereby developed a purely organic optical O2 sensor by embedding polyimide-based photoemitters within a poly(vinyl alcohol) (PVA) matrix. The photoemitters are synthesized through one-pot hydrothermal reactions. They have a lifetime of room temperature phosphorescence (RTP) of up to a few microseconds (μs) when they are embedded into the polymer matrix. Our results demonstrate that the photoemitters have higher sensitivity and broader sensing range to O2 if they are synthesized with longer reaction times because they possess a more rigid polyimide structure. The O2 sensor with such optimized photoemitters embedded in the polymer matrix exhibits continuous and broad-range O2 sensing in the range of 0-16% O2. The Stern-Volmer quenching constant (Ksv) was calculated to be 0.2351 kPa-1 for the linear response range of 0-4% O2. Moreover, the O2 sensor can be repetitively used at least 10 times in the linear range (0-4% O2) or beyond the linear range (up to 21% O2). The metal-free, purely organic sensors that enable the continuous and repetitive detection of O2 within a relevant O2 sensing range are appealing especially for monitoring packaged food, biomonitoring, and biosensing., ACS Applied Polymer Materials, 3 (5), ISSN:2637-6105

Dynamic controlling the nanoscale presentation of synergistic ligands to stem cells by biomimetic single-chain materials can provide critical insights to understand the molecular crosstalk underlying cells and their extracellular matrix. Here, a stimuli-responsive single-chain macromolecular nanoregulator with conformational dynamics is fabricated based on an advanced scale-up single polymeric chain nanogel (SCNG). Such a carefully designed SCNG is capable of mediating a triggered copresentation of the master and cryptic ligands in a single molecule to elicit the synergistic crosstalk between different intracellular signaling pathways, thereby considerably boosting the bioactivity of the presented ligands. This controllable nanoswitching-on of cell-adhesive ligands' presentation allows the regulation of cell adhesion and fate from molecular scale. The modular nature of this synthetic macromolecular nanoregulator makes it a versatile nanomaterial platform to assist basic and fundamental studies in a wide array of research topics.

Carbohydrates are the most abundant and one of the most important biomacromolecules in Nature. Except for energy-related compounds, carbohydrates can be roughly divided into two categories: Carbohydrates as matter and carbohydrates as information. As matter, carbohydrates are abundantly present in the extracellular matrix of animals and cell walls of various plants, bacteria, fungi, etc., serving as scaffolds. Some commonly found polysaccharides are featured as biocompatible materials with controllable rigidity and functionality, forming polymeric biomaterials which are widely used in drug delivery, tissue engineering, etc. As information, carbohydrates are usually referred to the glycans from glycoproteins, glycolipids, and proteoglycans, which bind to proteins or other carbohydrates, thereby meditating the cell-cell and cell-matrix interactions. These glycans could be simplified as synthetic glycopolymers, glycolipids, and glycoproteins, which could be afforded through polymerization, multistep synthesis, or a semisynthetic strategy. The information role of carbohydrates can be demonstrated not only as targeting reagents but also as immune antigens and adjuvants. The latter are also included in this review as they are always in a macromolecular formulation. In this review, we intend to provide a relatively comprehensive summary of carbohydrate-based macromolecular biomaterials since 2010 while emphasizing the fundamental understanding to guide the rational design of biomaterials. Carbohydrate-based macromolecules on the basis of their resources and chemical structures will be discussed, including naturally occurring polysaccharides, naturally derived synthetic polysaccharides, glycopolymers/glycodendrimers, supramolecular glycopolymers, and synthetic glycolipids/glycoproteins. Multiscale structure-function relationships in several major application areas, including delivery systems, tissue engineering, and immunology, will be detailed. We hope this review will provide valuable information for the development of carbohydrate-based macromolecular biomaterials and build a bridge between the carbohydrates as matter and the carbohydrates as information to promote new biomaterial design in the near future.

Hydrogels have been widely used as the carrier material of therapeutic cell and drugs for articular cartilage repair. We previously demonstrated a unique host-guest macromer (HGM) approach to prepare mechanically resilient, self-healing and injectable supramolecular gelatin hydrogels free of chemical crosslinking. In this work, we show that compared with conventional hydrogels our supramolecular gelatin hydrogels mediate more sustained release of small molecular (kartogenin) and proteinaceous (TGF-β1) chondrogenic agents, leading to enhanced chondrogenesis of the encapsulated human bone marrow-derived mesenchymal stem cells (hBMSCs) in vitro and in vivo. More importantly, the supramolecular nature of our hydrogels allows injection of the pre-fabricated hydrogels containing the encapsulated hBMSCs and chondrogenic agents, and our data show that the injection process has little negative impact on the viability and chondrogenesis of the encapsulated cells and subsequent neocartilage development. Furthermore, the stem cell-laden supramolecular hydrogels administered via injection through a needle effectively promote the regeneration of both hyaline cartilage and subchondral bone in the rat osteochondral defect model. These results demonstrate that our supramolecular HGM hydrogels are promising delivery biomaterials of therapeutic agents and cells for cartilage repair via minimally invasive procedures. This unique capability of injecting cell-laden hydrogels to target sites will greatly facilitate stem cell therapies.

Resembling soft tissues, stretchable hydrogels are promising biomaterials for many biomedical applications due to their excellent mechanical robustness. However, conventional stretchable hydrogels with a synthetic polymer matrix are usually bioinert. The lack of cell and tissue adhesiveness of such hydrogels limits their applications. An easy but reliable postgelation functionalization method is desirable. Herein, we report the fabrication of stretchable supramolecular hydrogels cross-linked by multivalent host-guest interactions. Such hydrogels containing thiourea ( TU) functionalities can be bioactivated with a catechol-modified peptide (Cat-RGD) via thiourea-catechol ( TU-Cat) coupling reaction. This postgelation bioactivation of the otherwise bioinert hydrogels not only conjugates bioactive ligands for cell attachment but also introduces and preserves the catechol structures for tissue adhesion. This straightforward fabrication and one-stone-two-bird bioactivation of the stretchable hydrogels may find broad applications in developing advanced soft biomaterials for tissue repair, wound dressing, and lesion sealing.

Intestinal anastomotic leaking, which involves the discharge of chemically aggressive, non‐sterile fluids into the abdomen, remains one of the most dreaded postoperative complications of abdominal surgery. Depending on the site and the patient condition, incidence ranging between 4% and 21% and mortality rates up to 27% are reported. Currently available surgical sealants only poorly address the issue, especially since most commonly used fibrin glues fail due to insufficient adhesion and chemical instability. Here, a chemically highly resistive, leak‐tight, and mucoadhesive hydrogel sealant, which is grafted on the surface of the intestinal wall using a mutually interpenetrating network that traverses hydrogel and tissue is presented. In contrast to clinically used fibrin‐based sealants (including Tachosil), the developed adhesive poly(acrylamide‐methyl acrylate‐acrylic acid) patch does not degrade and exhibits strong tissue adhesion even when exposed to intestinal fluid. The biocompatible hydrogel patch effectively seals anastomotic leaks in ex vivo intestinal models, greatly surpassing commercial sealants (time to patch‐failure >24 h compared to 5 min for commonly used Tachosil). Importantly, the developed adhesive patch paves the way for the application of both mechanically and chemically robust sealants suitable for the treatment and prevention of intestinal leaks. © 2021 Wiley‐VCH GmbH., Advanced Functional Materials, 31 (16), ISSN:1616-3028, ISSN:1616-301X

Hydrogels are soft materials used in an array of biomedical applications. However, the in situ formation of hydrogels at target sites, particularly in dynamic in vivo environments, usually requires a prolonged gelation time and results in poor adhesion. These limitations cause considerable loss of both hydrogel mass and encapsulated therapeutic cargoes, thereby compromising treatment outcomes. Here, we report the development of a hydrogel based on thiourea-catechol reaction to enhance the bioadhesion. Compared with classical bioadhesive hydrogels, our hydrogels show enhanced mechanical properties, exceedingly short curing time, and pH-independent gelation with a much lower oxidant concentration. We further report the robust adhesion of our hydrogels to acidic gastric tissues and easy delivery to the porcine stomach via endoscopy. The delivered hydrogels adhered to ulcer sites in vivo for at least 48 hours. Hydrogel treatment of gastric ulcers in rodent and porcine models accelerated ulcer healing by suppressing inflammation and promoting re-epithelization and angiogenesis. The improved retention of proregenerative growth factors and reduced exposure to external catabolic factors after hydrogel application may contribute to the observed therapeutic outcomes. Our findings reveal a promising biomaterial-based approach for treating gastrointestinal diseases.

Biomimetic hydrogels with hierarchical network structures are promising biomaterials for tissue engineering due to their unique mechanical properties. One successful biomimetic strategy for facile construction of high-performance hydrogels is to incorporate reversible crosslinks as sacrificial bonds into chemical polymer networks. By mimicking the unfolding-refolding functions of the skeletal muscle protein titin, the reversible crosslinks can reinforce the otherwise weak and brittle hydrogels. However, the contribution of multivalent reversible crosslinks to the overall hydrogel mechanical properties has rarely been investigated. Herein we present the biomimetic hydrogels with multivalent host-guest interactions as reversible crosslinks, which provide not only energy storage capacity, but also elevated energy dissipation capacity to the dually crosslinked networks, therefore leading to the improved hydrogel ductility and tensile strength. Our results also reveal the manner of multivalent host-guest crosslinks contributing to the hydrogel mechanical properties, including gelation rate, energy storage and dissipation, tensile hysteresis, and fast spontaneous recovery.

Dynamic controlling the nanoscale presentation of synergistic ligands to stem cells by biomimetic single-chain materials can provide critical insights to understand the molecular crosstalk underlying cells and their extracellular matrix. Here, a stimuli-responsive single-chain macromolecular nanoregulator with conformational dynamics is fabricated based on an advanced scale-up single polymeric chain nanogel (SCNG). Such a carefully designed SCNG is capable of mediating a triggered copresentation of the master and cryptic ligands in a single molecule to elicit the synergistic crosstalk between different intracellular signaling pathways, thereby considerably boosting the bioactivity of the presented ligands. This controllable nanoswitching-on of cell-adhesive ligands' presentation allows the regulation of cell adhesion and fate from molecular scale. The modular nature of this synthetic macromolecular nanoregulator makes it a versatile nanomaterial platform to assist basic and fundamental studies in a wide array of research topics.

Poly(ethylene glycol) (PEG)-based hydrogels are promising materials for biomedical applications because of their excellent hydrophilicity and biocompatibility. However, conventional chemically cross-linked PEG hydrogels are brittle under mechanical loading. The mechanical resilience and rapid recovery abilities of hydrogel implants are critical in load-bearing tissues, such as articular cartilage, which are routinely subjected to cyclic loadings of high magnitude and frequency. Here, we report the fabrication of novel supramolecular PEG hydrogels by polymerizing N,N-dimethylacrylamide with supramolecular cross-linkers self-assembled from adamantane-grafted PEG and mono-acrylated β-cyclodextrin. The resultant PEG–ADA supramolecular hydrogels exhibit substantial deformability, excellent capacity to dissipate massive amounts of loading energy, and have a rapid, full recovery during excessive, ultrafast, and non-resting cyclic compression. Furthermore, the energy dissipation capacity of the PEG–ADA (adamantane-grafted Poly(ethylene glycol)) hydrogels can be regulated by changing the concentration, molecular weight and cross-linking density of PEG. According to in vitro cell metabolism and viability tests, the PEG–ADA hydrogels are non-cytotoxic. When placed over a monolayer of myoblasts that were subjected to instantaneous compressive loading, the PEG–ADA hydrogel cushion significantly enhanced cell survival under this deleterious mechanical insult compared with the effects of the conventional PEG hydrogel. Therefore, PEG–ADA hydrogels are promising prosthetic biomaterials for the repair and regeneration of load-bearing tissues. Soft, water-filled polymers known as hydrogels may find roles as implants in load-bearing joints thanks to advances in strain-resistant chemical networks. Most hydrogels contain molecular components called cross-links that connect long polymer chains into a sturdy network. A team led by Bin Li at China’s Soochow University in Suzhou and Liming Bian at the Chinese University of Hong Kong have developed a hydrogel cross-linking system based on a pair of molecules, cyclodextrin and adamantine, that attach to each other using physical forces instead of conventional chemical bonds. When exposed to a mechanical load, these cross-links quickly separate to dissipate energy, then re-associate to preserve the original gel network. Compression experiments revealed the new material could cushion the force applied to mouse muscle cell cultures and reduced cell death rates by 30% compared with conventional hydrogels. This study is to investigate and systemically study the mechanical performance of supramolecular PEG hydrogels in comparison with those of the chemical hydrogels cross-linked by conventional PEG diacrylate (PEGDA). The supramolecular cross-links based on the host-guest complexation significantly enhance the energy dissipation, fatigue resistance, and stress-relaxation of supramolecular PEG hydrogels and protect cells from deleterious mechanical insults. This research provides valuable guidance on the design of prosthetic hydrogels for loading bearing implantations sites with surrounding mechanosensitive cells or tissues and critical insights on the translation of host-guest hydrogels to biomedical applications.

Fatigue resistance of hydrogels is critical to their applications in load-bearing sites of soft tissues that are usually subjected to continuous loadings, such as joint cartilage. However, hydrogels usually swell under physiological conditions and exhibit inevitable fatigue during excessive mechanical loadings. Here we show that hydrogels cross-linked by multivalent host–guest interactions can effectively dissipate a large fraction of the loading energy (>50%) under excessive compressions (over 80% strain, 1000 cycles) despite their high water contents (95%) under physiological conditions. No fatigue is observed in such highly swollen hydrogels during continuous cyclic compressions. We demonstrate that such hydrogels can be used as 3D cell carriers for excessive mechanical stimulation of the encapsulated stem cells, making them promising soft biomaterials for tissue engineering.

Cellular adhesion is regulated by the dynamic ligation process of surface receptors, such as integrin, to adhesive motifs, such as Arg-Gly-Asp (RGD). Remote control of adhesive ligand presentation using external stimuli is an appealing strategy for the temporal regulation of cell-implant interactions in vivo and was recently demonstrated using photochemical reaction. However, the limited tissue penetration of light potentially hampers the widespread applications of this method in vivo. Here, we present a strategy for modulating the nanoscale oscillations of an integrin ligand simply and solely by adjusting the frequency of an oscillating magnetic field to regulate the adhesion and differentiation of stem cells. A superparamagnetic iron oxide nanoparticle (SPION) was conjugated with the RGD ligand and anchored to a glass substrate by a long flexible poly(ethylene glycol) linker to allow the oscillatory motion of the ligand to be magnetically tuned. In situ magnetic scanning transmission electron microscopy and atomic force microscopy imaging confirmed the nanoscale motion of the substrate-tethered RGD-grafted SPION. Our findings show that ligand oscillations under a low oscillation frequency (0.1 Hz) of the magnetic field promoted integrin-ligand binding and the formation and maturation of focal adhesions and therefore the substrate adhesion of stem cells, while ligands oscillating under high frequency (2 Hz) inhibited integrin ligation and stem cell adhesion, both in vitro and in vivo. Temporal switching of the multimodal ligand oscillations between low- and high-frequency modes reversibly regulated stem cell adhesion. The ligand oscillations further induced the stem cell differentiation and mechanosensing in the same frequency-dependent manner. Our study demonstrates a noninvasive, penetrative, and tunable approach to regulate cellular responses to biomaterials in vivo. Our work not only provides additional insight into the design considerations of biomaterials to control cellular adhesion in vivo but also offers a platform to elucidate the fundamental understanding of the dynamic integrin-ligand binding that regulates the adhesion, differentiation, and mechanotransduction of stem cells.

Microfluidic wet spinning has gained increasing interest in recent years as an alternative to conventional wet spinning by offering higher control in fiber morphology and a gateway for the development of multi-material fibers. Conventionally, microfluidic chips used to create such fibers are fabricated by soft lithography, a method that requires both time and investment in necessary cleanroom facilities. Recently, additive manufacturing techniques were investigated for rapid and cost-efficient prototyping. However, these microfluidic devices are not yet matching the resolutions and tolerances offered by soft lithography. Herein, we report a facile and rapid method using selected arrays of hypodermic needles as templates within a silicone elastomer matrix. The produced microfluidic spinnerets display co-axially aligned circular channels. By simulation and flow experiments, we prove that these devices can maintain laminar flow conditions and achieve precise 3D hydrodynamic focusing. The devices were tested with a commercial polyurethane formulation to demonstrate that fibers with desired morphologies can be produced by varying the degree of hydrodynamic focusing. Thanks to the adaptability of this concept to different microfluidic spinneret designs&mdash, as well as to its transparency, ease of fabrication, and cost-efficient procedure&mdash, this device sets the ground for transferring microfluidic wet spinning towards industrial textile settings.

A rational approach promotes mechano-dependent osteogenesis and effective bone regeneration with conjugated biomimetic peptide., Noncanonical Wnt signaling in stem cells is essential to numerous developmental events. However, no prior studies have capitalized on the osteoinductive potential of noncanonical Wnt ligands to functionalize biomaterials in enhancing the osteogenesis and associated skeleton formation. Here, we investigated the efficacy of the functionalization of biomaterials with a synthetic Wnt5a mimetic ligand (Foxy5 peptide) to promote the mechanosensing and osteogenesis of human mesenchymal stem cells by activating noncanonical Wnt signaling. Our findings showed that the immobilized Wnt5a mimetic ligand activated noncanonical Wnt signaling via the up-regulation of Disheveled 2 and downstream RhoA-ROCK signaling, leading to enhanced intracellular calcium level, F-actin stability, actomyosin contractility, and cell adhesion structure development. This enhanced mechanotransduction in stem cells promoted the in vitro osteogenic lineage commitment and the in vivo healing of rat calvarial defects. Our work provides valuable guidance for the developmentally inspired design of biomaterials for a wide array of therapeutic applications.

The engineering of catechol-based hydrogels to bind to wet biological tissues with high adhesion energy remains a challenge. Herein, fast quinone-nucleophile coupling and dynamic boronate ester bond were used to enhance the interfacial adhesion and bulk cohesion of our dual-crosslinked hydrogels, respectively, for fabricating mussel-mimetic tough adhesives.

Although considered promising materials for assisting organ regeneration, few hydrogels meet the stringent requirements of clinical translation on the preparation, application, mechanical property, bioadhesion, and biocompatibility of the hydrogels. Herein, we describe a facile supramolecular approach for preparing gelatin hydrogels with a wide array of desirable properties. Briefly, we first prepare a supramolecular gelatin macromer via the efficient host-guest complexation between the aromatic residues of gelatin and free diffusing photo-crosslinkable acrylated β-cyclodextrin (β-CD) monomers. The subsequent crosslinking of the macromers produces highly resilient supramolecular gelatin hydrogels that are solely crosslinked by the weak host-guest interactions between the gelatinous aromatic residues and β-cyclodextrin (β-CD). The obtained hydrogels are capable of sustaining excessive compressive and tensile strain, and they are capable of quick self healing after mechanical disruption. These hydrogels can be injected in the gelation state through surgical needles and re-molded to the targeted geometries while protecting the encapsulated cells. Moreover, the weak host-guest crosslinking likely facilitate the infiltration and migration of cells into the hydrogels. The excess β-CDs in the hydrogels enable the hydrogel-tissue adhesion and enhance the loading and sustained delivery of hydrophobic drugs. The cell and animal studies show that such hydrogels support cell recruitment, differentiation, and bone regeneration, making them promising carrier biomaterials of therapeutic cells and drugs via minimally invasive procedures.

Mimicking the diverse glyco-conjugate structures in nature is always the dream of scientists. Right now, hierarchical self-assembled structures of natural conjugates of peptides and sugars could not easily be achieved via linear glycopolypeptide with monosaccharides as attachments. In this work, by using a series of well-designed alternating amphiphilic glycopolypeptide brushes (AAGBs) with pendants of glycodendrons and short peptides, various self-assembled morphologies were achieved, including nanowires, nanoribbon, and compound micelles mainly depending on the number ratio of the sugar units to the amino acids species (S/F). Among these morphologies, nanowire attracted our great attention. TEM studies demonstrated that it is formed via a hierarchical self-assembly, i.e., a series of successive processes, including micellization, micelles alignment forming nanofilament, branching of the nanofilaments by micelles, and finally nanowire formation. As far as we know, such hierarchical self-assembly process with high complexity has not been observed in literature for glycopolypeptides even polypeptides, which will deepen our understanding on self-assembly mechanism of natural glyco-conjugates and expand the library of biomimetic materials.

Hydrogels are emerging biomaterials with desirable physicochemical characteristics. Doping of metal ions such as Ca2+ , Mg2+ , and Fe2+ provides the hydrogels with unique attributes, including bioactivity, conductivity, and tunability. Traditionally, this doping is achieved by the interaction between metal ions and corresponding ligands or the direct incorporation of as-prepared metal-based nanoparticles (NPs). However, these approaches rely on a complex and laborious preparation and are typically restricted to few selected ion species. Herein, by mixing aqueous solutions of ligands (bisphosphonates, BPs), polymer grafted with ligands, and metal ions, a series of self-assembled metallic-ion nanocomposite hydrogels that are stabilized by the in situ formed ligand-metal ion (BP-M) NPs are prepared. Owing to the universal coordination between BPs and multivalent metal ions, the strategy is highly versatile and can be generalized for a wide array of metal ions. Such hydrogels exhibit a wide spectrum of mechanical properties and remarkable dynamic properties, such as excellent injectability, rapid stress relaxation, efficient ion diffusion, and triggered disassembly for harvesting encapsulated cells. Meanwhile, the hydrogels can be conveniently coated or patterned onto the surface of metals via electrophoresis. This work presents a universal strategy to prepare designer nanocomposite materials with highly tunable and dynamic behaviors.

Rigorous peer-review is the corner-stone of high-quality academic publishing [...]

Injectable hydrogel adhesives, especially those that can strongly adhere to tissues and feature near-native tissue mechanical properties, are desirable biomaterials for tissue repair. Compared to nonadhesive injectable hydrogels for minimally invasive delivery of therapeutic agents, they can better retain the delivered agents at targeted tissue locations and provide additional local physical barriers. However, regardless of recent advances, an ideal injectable hydrogel adhesive with both proper adhesion and mechanical matching between hydrogels and tissues is yet to be demonstrated with cytocompatible and efficient in situ curing methods. Inspired by marine mussels, where different mussel foot proteins (Mfps) function cooperatively to achieve excellent wet adhesion, we herein report a dual-mode-mimicking strategy by modifying gelatin (Gel) biopolymers with a single-type thiourea-catechol (TU-Cat) functionality to mimic two types of Mfps and their mode of action. This strategy features a minor, yet impactful modification of biopolymers, which gives access to collective properties of an ideal injectable hydrogel adhesive. Specifically, with TU-Cat functionalization of only ∼0.4-1.2 mol % of total amino acid residues, the Mfp-mimetic gelatin biopolymer (Gel-TU-Cat) can be injected and cured rapidly under mild and cytocompatible conditions, giving rise to tissue adhesive hydrogels with excellent matrix ductility, proper wet adhesion, and native tissue-like stress relaxation behaviors. Such a set of properties originating from our novel dual-mode-mimicking strategy makes the injectable hydrogel adhesive a promising platform for cell delivery and tissue repair.

Biopolymer-based supramolecular hydrogels cross-linked by host–guest interactions are usually mechanically weak as shown in “inverted vials” instead of freestanding 3D constructs. Herein, we describe a novel host–guest macromer (HGM) approach for preparation of biopolymer-based freestanding supramolecular hydrogels. Host–guest macromers are formed by molecular self-assembly between adamantane-functionalized hyaluronic acid (ADxHA) guest polymers and monoacrylated β-cyclodextrins (mono-Ac-βCD) host monomers. Supramolecular hydrogels are readily prepared by UV-induced polymerization of the preassembled host–guest macromers. Such hydrogels are soely cross-linked by in situ formed multivalent host–guest nanoclusters and show significantly reinforced mechanical properties yet still retain desirable supramolecular features. They can self-heal and be remolded into freestanding 3D constructs which afford effective protection on the encapsulated stem cells during the compression remolding, making them promising ca...

Mussel adhesion has inspired the development of catechol-based adhesive polymers. However, conventional strategies require basic pH conditions and lead to the loss of adhesion. To solve the problem, we report the first attempt to use thiourea-functionalized polymers for preserving hydrogel adhesion. We believe that this simple thiourea-quinone coupling chemistry is instrumental to synthetic adhesive materials.

The capability of monitoring the differentiation process in living stem cells is crucial to the understanding of stem cell biology and the practical application of stem-cell-based therapies, yet conventional methods for the analysis of biomarkers related to differentiation require a large number of cells as well as cell lysis. Such requirements lead to the unavoidable loss of cell sources and preclude real-time monitoring of cellular events. In this work, we report the detection of microRNAs (miRNAs) in living human mesenchymal stem cells (hMSCs) by using polydopamine-coated gold nanoparticles (Au@PDA NPs). The PDA shell facilitates the immobilization of fluorescently labeled hairpin DNA strands (hpDNAs) that can recognize specific miRNA targets. The gold core and PDA shell quench the fluorescence of the immobilized hpDNAs, and subsequent binding of the hpDNAs to the target miRNAs leads to their dissociation from Au@PDA NPs and the recovery of fluorescence signals. Remarkably, these Au@PDA-hpDNA nanoprobes can naturally enter stem cells, which are known for their poor transfection efficiency, without the aid of transfection agents. Upon cellular uptake of these nanoprobes, we observe intense and time-dependent fluorescence responses from two important osteogenic marker miRNAs, namely, miR-29b and miR-31, only in hMSCs undergoing osteogenic differentiation and living primary osteoblasts but not in undifferentiated hMSCs and 3T3 fibroblasts. Strikingly, our nanoprobes can afford long-term tracking of miRNAs (5 days) in the differentiating hMSCs without the need of continuously replenishing cell culture medium with fresh nanoprobes. Our results demonstrate the capability of our Au@PDA-hpDNA nanoprobes for monitoring the differentiation status of hMSCs (i.e., differentiating versus undifferentiated) via the detection of specific miRNAs in living stem cells. Our nanoprobes show great promise in the investigation of the long-term dynamics of stem cell differentiation, identification and isolation of specific cell types, and high-throughput drug screening.

Cellular behaviors, such as differentiation, are regulated by complex ligation processes involving cell surface receptors, which can be activated by various divalent metal cations. The design of nanoparticle for co-delivery of ligand and ligation activator can offer a novel strategy to synergistically stimulate ligation processes in vivo. Here, we present a novel layered double hydroxide (LDH)-based nanohybrid (MgFe-Ado-LDH), composed of layered MgFe hydroxide nanocarriers sandwiching the adenosine cargo molecule, maintained through an electrostatic balance, to co-deliver the adenosine (Ado) ligand from the interlayer spacing and the Mg 2+ ion (ligation activator) through the dissolution of the MgFe nanocarrier itself. Our findings demonstrate that the MgFe-Ado-LDH nanohybrid promoted osteogenic differentiation of stem cells through the synergistic activation of adenosine A2b receptor (A2bR) by the dual delivery of adenosine and Mg 2+ ions, outperforming direct supplementation of adenosine alone. Furthermore, the injection of the MgFe-Ado-LDH nanohybrid and stem cells embedded within hydrogels promoted the healing of rat tibial bone defects through the rapid formation of fully integrated neo-bone tissue through the activation of A2bR. The newly formed bone tissue displayed the key features of native bone, including calcification, mature tissue morphology, and vascularization. This study demonstrates a novel and effective strategy of bifunctional nanocarrier-mediated delivery of ligand (cargo molecule) and activation of its ligation to receptor by the nanocarrier itself for synergistically inducing stem cell differentiation and tissue healing in vivo, thus offering novel design of biomaterials for regenerative medicine. Refereed/Peer-reviewed

Macromolecular self-assembly (MSA) has been an active and fruitful research field since the 1980s, especially in this new century, which is promoted by the remarkable developments in controlled radical polymerization in polymer chemistry, etc. and driven by the demands in bio-related investigations and applications. In this review, we try to summarize the trends and recent progress in MSA in relation to biomimetic chemistry and bio-inspired materials. Our paper covers representative achievements in the fabrication of artificial building blocks for life, cell-inspired biomimetic materials, and macromolecular assemblies mimicking the functions of natural materials and their applications. It is true that the current status of the deliberately designed and obtained nano-objects based on MSA including a variety of micelles, multicompartment vesicles, and some hybrid and complex nano-objects is at their very first stage to mimic nature, but significant and encouraging progress has been made in achieving a certain similarity in morphologies or properties to that of natural ones. Such achievements also demonstrate that MSA has played an important and irreplaceable role in the grand and long-standing research of biomimetic and bio-inspired materials, the future success of which depends on mutual and persistent efforts in polymer science, material science, supramolecular chemistry, and biology.

Supramolecular conjugation between native protein concanavalin A (ConA) and synthetic polymer PEG (polyethylene glycol) was achieved by dual molecular recognition interactions via a linker, βCD-Man, of which β-cyclodextrin (βCD) and α-mannopyranoside (Man) recognized the adamantane (Ada) end of PEG and lectin ConA orthogonally. Further self-assembly of the resultant supra-conjugates of ConA-PEG was induced by the addition of αCD, which was selectively threaded by PEG chains, leading to nanoparticles in dilute solution or hydrogel at a higher concentration. The moduli of the obtained hydrogel were three magnitudes higher than those of the control sample without ConA, showing the dramatic cross-linking effect of ConA achieved by its rather weak interaction with α-d-mannopyranoside.

The well-known coil-to-globule transition of poly( N -isopropyl acrylamide) (PNIPAM) at its LCST lasts as short as hundred of seconds with fully reversibility. However, for the PNIPAM-containing block copolymers, thermal transformation from micelles to vesicles caused by the conformation transition of PNIPAM took as long as several weeks, even at the temperatures much higher than the LCST, and without satisfactory reversibility. In the literature, this slow process has been attributed to the strong interchain hydrogen bonding in PNIPAM, which retards the transition. In this work, asymmetrically modified PNIPAM (Mw 10K), i.e . C 12 -PNIPAM-CA with a hydrophobic hydrocarbon chain –C 12 H 25 ( C 12 ) at one end and a hydrophilic carboxyl group –COOH ( CA ) at the other, was prepared and found to form micelles with a core of the lightly associated hydrocarbon chains. When temperature is increased to the LCST of PNIPAM, the transformation from micelles to vesicles can be realized within 30 min, while the reverse process only takes a few minutes. Based on full monitoring of the transition process, it is proposed that the micelles serve as building blocks in constructing the vesicles via processes of combination, fusion, and etc ., in which only local conformation adjustment of PNIPAM is involved. Therefore, reducing the restriction to the conformation change of PNIPAM chains, which is imposed by the micellar core, is one of the key factors in realizing the fast transition.

Poly (ethylene glycol) (PEG) based hydrogels have been widely used in many biomedical applications such as regenerative medicine due to their good biocompatibility and negligible immunogenicity. However, bioactivation of PEG hydrogels, such as conjugation of bioactive biomolecules, is usually necessary for cell-related applications. Such biofunctionalization of PEG hydrogels generally involves complicated and time-consuming bioconjugation procedures. Herein, we describe the facile preparation of bioactive nanocomposite PEG hydrogel crosslinked by the novel multifunctional nanocrosslinkers, namely polydopamine-coated layered double hydroxides (PD-LDHs). The catechol-rich PD-LDH nanosheets not only act as effective nanocrosslinkers reinforcing the mechanical strength of the hydrogel, but also afford the hydrogels with robust bioactivity and bioadhesion via the cortical-mediated couplings. The obtained nanocomposite PEG hydrogels with the multifunctional PD-LDH crosslinking domains show tunable mechanical properties, self-healing ability, and bioadhesion to biological tissues. Furthermore, these hydrogels also promote the sequestration of proteins and support the osteogenic differentiation of human mesenchymal stem cells without any further bio-functionalization. Such facile preparation of bioactive and bioadhesive PEG hydrogels have rarely been achieved and may open up a new avenue for the design of nanocomposite PEG hydrogels for biomedical applications.

With their unique properties of self-healing and viscoelasticity, physically crosslinked supramolecular hydrogels are promising materials for soft robotics, wearable electronics and biomedical applications. However, the weak mechanical properties of supramolecular hydrogels, especially those prepared with natural polymers, limit their wide-spread application, and swelling is one of the key factors that contributes to the weakening of hydrogels. Herein, we utilize a simple one-pot solvent exchange method to prepare non-swellable, thermoplastic and tough supramolecular gelatin hydrogels based on two synergistic physical crosslinkings, namely, the self-assembled tri-helix structure of gelatin and the hydrophobic aggregation of gelatin-grafted and free hydrophobic motifs. The obtained hydrogels possess a stable water content above 70% with extended incubation in water. These hydrogels are highly malleable upon heating but are extremely stretchable and tough after cooling to room temperature. Furthermore, the supramolecular gelatin hydrogels exhibit robust adhesion to various material surfaces and minimal cytotoxicity. A method for synthesizing a mechanically robust soft material that can heal itself has been developed by scientists in Hong Kong and China. Self-healing hydrogels are so called because crosslinked polymers can spontaneously form new bonds when old ones break. They are soft and flexible, making them ideal for soft robots and biomedical applications. However, they can swell rapidly when wet, which undermines their mechanical strength. Liming Bian from the Chinese University of Hong Kong and colleagues created a non-swellable, stretchable and tough hydrogel using a simple one-pot technique. They reduced swelling by harnessing two types of crosslinking: the self-assembled tri-helix crosslinking of gelatin and the aggregation of hydrophobic groups on the gelatin molecule. The supramolecular gelatin hydrogel is malleable when heated but extremely stretchable and tough once cooled. A simple one-pot solvent exchange method is developed to prepare non-swellable, thermoplastic and tough supramolecular gelatin hydrogels based on two synergistic physical crosslinking, namely, the self-assembled tri-helix structure of gelatin and hydrophobic aggregation of gelatin-grafted and free hydrophobic motifs. The obtained hydrogels possess stable water content >70% with extended incubation in water and these hydrogels are highly malleable upon heating but are extremely stretchable and tough after cooling to room temperature. Furthermore, the supramolecular gelatin hydrogels exhibit robust adhesion to various material surfaces and minimal cytotoxicity.

Macromolecular self-assembly (MSA) has been an active and fruitful research field since the 1980s, especially in this new century, which is promoted by the remarkable developments in controlled radical polymerization in polymer chemistry, etc. and driven by the demands in bio-related investigations and applications. In this review, we try to summarize the trends and recent progress in MSA in relation to biomimetic chemistry and bio-inspired materials. Our paper covers representative achievements in the fabrication of artificial building blocks for life, cell-inspired biomimetic materials, and macromolecular assemblies mimicking the functions of natural materials and their applications. It is true that the current status of the deliberately designed and obtained nano-objects based on MSA including a variety of micelles, multicompartment vesicles, and some hybrid and complex nano-objects is at their very first stage to mimic nature, but significant and encouraging progress has been made in achieving a certain similarity in morphologies or properties to that of natural ones. Such achievements also demonstrate that MSA has played an important and irreplaceable role in the grand and long-standing research of biomimetic and bio-inspired materials, the future success of which depends on mutual and persistent efforts in polymer science, material science, supramolecular chemistry, and biology.

Inorganic nanoparticles can self-assemble into various supra-structures, among which vesicles are seldom reported. In this paper, a reversible self-assembly of gold nanoparticles to vesicles, mediated by double hydrophilic block copolymers, was carried out in pure water under the stimulus of temperature.