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Abstract Myocardial infarction (MI) is a leading cause of death globally. Stem cell therapy is considered a potential strategy for MI treatment. Transplantation of classic stem cells including embryonic, induced pluripotent and cardiac stem cells exhibited certain repairing effect on MI via supplementing cardiomyocytes, however, their clinical applications were blocked by problems of cell survival, differentiation, functional activity and also biosafety and ethical concerns. Here, we introduced human amniotic epithelial stem cells (hAESCs) featured with immunomodulatory activities, immune-privilege and biosafety, for constructing a stem cell cardiac patch based on porous antioxidant polyurethane (PUR), which demonstrated decent hAESCs compatibility. In rats, the administration of PUR-hAESC patch significantly reduced fibrosis and facilitated vascularization in myocardium after MI and consequently improved cardiac remodeling and function. Mechanistically, the patch provides a beneficial microenvironment for cardiac repair by facilitating a desirable immune response, paracrine modulation and limited oxidative milieu. Our findings may provide a potential therapeutic strategy for MI.

Valvular heart disease (VHD) is a significant public health threat, with heart valve replacement surgery being the standard treatment for severe cases. Despite of advancements in artificial heart valves, their longevity remains limited due to in vivo degeneration. In consequence, there is an urgent need for effective methods to enhance the durability of artificial heart valves. Because oxidative stress (OS) is a key driving factor contributing to the failure of cardiovascular implants, this review focuses on how OS plays a critical role in heart valve degeneration, and its relationship with four major physiological mechanisms: extracellular matrix (ECM) degradation, immune response, thrombosis and lipid metabolism. By highlighting OS as a potential therapeutic target, we explore surface modification strategies that incorporate these fundamental mechanisms, refer to passive approaches including OS elimination, immunosuppression, blocking surface-degradation active groups, and anticoagulation, and active approaches such as regulating biological function recovery, and surface endothelial remodeling. These strategies aim to delay or reverse artificial valves degeneration via combining with the perspective of OS regulation, ultimately extending the prognosis period after heart valve replacement surgeries.

Abstract HIF‐1α (hypoxia induced factor‐1α), a vital protective signal against hypoxia, has a short lifetime after myocardial infarction (MI). Increasing HIF‐1α stability by inhibiting its hydroxylation with prolyl hydroxylases inhibitors such as DPCA (1,4‐dihydrophenonthrolin‐4‐one‐3‐carboxylic acid) presents positive results. However, the optimal inhibitor administration profile for MI treatment is still unexplored. Here, injectable, thermosensitive hydrogels with programmable DPCA release are designed and synthesized. Hydrogel degradation and slow DPCA release are coupled to form a feedback loop by attaching pendant DPCA to polymer backbone, which serve as additional crosslinking points through π–π and hydrophobic interactions. Pendant carboxyl groups are added to the copolymer to accelerate DPCA release. Burst release in the acute phase for myocardial protection and extended near zero‐order release across the inflammatory and fibrotic phases with different rates are achieved. All DPCA‐releasing hydrogels upregulate HIF‐1α, decrease apoptosis, promote angiogenesis, and stimulate cardiomyocyte proliferation, leading to preserved cardiac function and ventricular geometry. Faster hydrogel degradation induced by faster DPCA release results in a HIF‐1α expression eight times of healthy control and better therapeutic effect in MI treatment. This research demonstrates the value of precise regulation of HIF‐1α expression in treating MI and other relevant diseases and provides an implantable device‐based modulation strategy.

Wound management is an important issue that places enormous pressure on the physical and mental health of patients, especially in cases of infection, where the increased inflammatory response could lead to severe hypertrophic scars (HSs). In this study, a hydrogel dressing was developed by combining the high strength and toughness, swelling resistance, antibacterial and antioxidant capabilities. The hydrogel matrix was composed of a double network of polyvinyl alcohol (PVA) and agarose with excellent mechanical properties. Hyperbranched polylysine (HBPL), a highly effective antibacterial cationic polymer, and tannic acid (TA), a strong antioxidant molecule, were added to the hydrogel as functional components. Examination of antibacterial and antioxidant properties of the hydrogel confirmed the full play of the efficacy of HBPL and TA. In the in vivo studies of methicillin-resistant Staphylococcus aureus (MRSA) infection, the hydrogel had shown obvious promotion of wound healing, and more profoundly, significant suppression of scar formation. Due to the common raw materials and simple preparation methods, this hydrogel can be mass produced and used for accelerating wound healing while preventing HSs in infected wounds.

Skin pathological fibrosis conditions, such as hypertrophic scars (HS) and keloids, where the scar tissue is raised and extends beyond the original wound boundary, are aesthetically unappealing and sometimes painful or itchy, significantly impacting the life quality of patients. In this review, the advances of nanobiomaterials in treating skin pathological fibrosis are summarized and discussed. The focus is on the therapeutic approaches to cellular and molecular targets of HS, highlighting the potential of nanotechnology in scar management. The biofunctional nanomaterials can modulate inflammation, regulate angiogenesis, and promote fibroblast apoptosis. The nanotechnology‐based drug delivery systems such as liposomes, ethosomes, and dendritic macromolecules can improve the solubility, stability, and efficacy of drugs, and enhance precise delivery, resulting in better outcomes in HS therapy. Integrating nanomaterials or nanostructures into hydrogels, nanofibers, and microneedles can enhance the biological functionality and maximize the therapeutic effect of nanoparticles (NPs) at the wound site. The important potential of nanotechnology‐based scar treatment should be further explored to overcome the current challenges and promote its application in clinical practice.

Abstract Shape-memory materials hold great potential to impart medical devices with functionalities useful during implantation, locomotion, drug delivery, and removal. However, their clinical translation is limited by a lack of non-invasive and precise methods to trigger and control the shape recovery, especially for devices implanted in deep tissues. In this study, the application of image-guided high-intensity focused ultrasound (HIFU) heating is tested. Magnetic resonance-guided HIFU triggered shape-recovery of a device made of polyurethane urea while monitoring its temperature by magnetic resonance thermometry. Deformation of the polyurethane urea in a live canine bladder (5 cm deep) is achieved with 8 seconds of ultrasound-guided HIFU with millimeter resolution energy focus. Tissue sections show no hyperthermic tissue injury. A conceptual application in ureteral stent shape-recovery reduces removal resistance. In conclusion, image-guided HIFU demonstrates deep energy penetration, safety and speed.

Temporomandibular joint (TMJ) cartilage repair poses a considerable clinical challenge, and tissue engineering has emerged as a promising solution. In this study, we developed an injectable reactive oxygen species (ROS)-responsive multifunctional hydrogel (RDGel) to encapsulate dental pulp stem cells (DPSCs/RDGel in short) for the targeted repair of condylar cartilage defect. The DPSCs/RDGel composite exhibited a synergistic effect in the elimination of TMJ OA (osteoarthritis) inflammation via the interaction between the hydrogel component and the DPSCs. We first demonstrated the applicability and biocompatibility of RDGel. RDGel encapsulation could enhance the anti-apoptotic ability of DPSCs by inhibiting P38/P53 mitochondrial apoptotic signal in vitro. We also proved that the utilization of DPSCs/RDGel composite effectively enhanced the expression of TMJOA cartilage matrix and promoted subchondral bone structure in vivo. Subsequently, we observed the synergistic improvement of DPSCs/RDGel composite on the oxidative stress microenvironment of TMJOA and its regulation and promotion of M2 polarization, thereby confirmed that M2 macrophages further promoted the condylar cartilage repair of DPSCs. This is the first time application of DPSCs/RDGel composite for the targeted repair of TMJOA condylar cartilage defects, presenting a novel and promising avenue for cell-based therapy.

Abstract Diagnostic and therapeutic illumination on internal organs and tissues with high controllability and adaptability in terms of spectrum, area, depth, and intensity remains a major challenge. Here, we present a flexible, biodegradable photonic device called iCarP with a micrometer scale air gap between a refractive polyester patch and the embedded removable tapered optical fiber. ICarP combines the advantages of light diffraction by the tapered optical fiber, dual refractions in the air gap, and reflection inside the patch to obtain a bulb-like illumination, guiding light towards target tissue. We show that iCarP achieves large area, high intensity, wide spectrum, continuous or pulsatile, deeply penetrating illumination without puncturing the target tissues and demonstrate that it supports phototherapies with different photosensitizers. We find that the photonic device is compatible with thoracoscopy-based minimally invasive implantation onto beating hearts. These initial results show that iCarP could be a safe, precise and widely applicable device suitable for internal organs and tissue illumination and associated diagnosis and therapy.

Spinal cord injury (SCI) is an overwhelming and incurable disabling event accompanied by complicated inflammation-related pathological processes, such as excessive reactive oxygen species (ROS) produced by the infiltrated inflammatory immune cells and released to the extracellular microenvironment, leading to the widespread apoptosis of the neuron cells, glial and oligodendroctyes. In this study, a thioketal-containing and ROS-scavenging hydrogel was prepared for encapsulation of the bone marrow derived mesenchymal stem cells (BMSCs), which promoted the neurogenesis and axon regeneration by scavenging the overproduced ROS and re-building a regenerative microenvironment. The hydrogel could effectively encapsulate BMSCs, and played a remarkable neuroprotective role in vivo by reducing the production of endogenous ROS, attenuating ROS-mediated oxidative damage and downregulating the inflammatory cytokines such as interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), resulting in a reduced cell apoptosis in the spinal cord tissue. The BMSCs-encapsulated ROS-scavenging hydrogel also reduced the scar formation, and improved the neurogenesis of the spinal cord tissue, and thus distinctly enhanced the motor functional recovery of SCI rats. Our work provides a combinational strategy against ROS-mediated oxidative stress, with potential applications not only in SCI, but also in other central nervous system diseases with similar pathological conditions.

Acute lung injury (ALI) is associated with excessive inflammatory response, leading to acute respiratory distress syndrome (ARDS) without timely treatment. A fewer effective drugs are available currently to treat the ALI/ARDS. Herein, a therapeutic nanoplatform with reactive oxygen species (ROS)-responsiveness was developed for the regulation of inflammation. Dexamethasone acetate (Dex) was encapsulated into poly(thioketal) polymers to form polymeric nanoparticles (NPs) (PTKNPs@Dex). The NPs were composed of poly(1,4-phenyleneacetonedimethylene thioketal) (PPADT) and polythioketal urethane (PTKU), in which the thioketal bonds could be cleaved by the high level of ROS at the ALI site. The PTKNPs@Dex could accumulate in the pulmonary inflammatory sites and release the encapsulated payloads rapidly, leading to the decreased ROS level, less generation of pro-inflammatory cytokines, and reduced lung injury and mortality of mice. RNA sequencing (RNA-seq) analysis showed that the therapeutic efficacy of the NPs was associated with the modulation of many immune and inflammation-linked pathways. These findings provide a newly developed nanoplatform for the efficient treatment of ALI/ARDS.

Abstract Transcatheter aortic valve replacement (TAVR) has the advantages of less trauma and faster postoperative recovery, which has brought the possibility to the elderly patient with valvular heart disease and is gradually replacing surgical aortic valve replacement (SAVR). The interventional valve used in TAVR needs to be compressed and transported through the catheter to the lesion site, and can still recover its original shape, structure and performance. This process requires that the material should be flexible, and the rigid mechanical valves in SAVR are not suitable. Recently, decellularized biological valves have been widely used in clinical practice, but their poor durability causes a limitation for long‐term implantation. Therefore, the anti‐calcification modification of biological valves and the design of new polymeric valves with good biostability have gained considerable attention. This review summarizes the calcification mechanism of biological valves and the research progress in anti‐calcification modification strategies. Besides, the development of new polymeric valves is included, with special attention to representative cases, such as polysiloxane, polytetrafluorethylene, poly(styrene‐block‐isobutylene‐block‐styrene), and polyurethane‐based materials. Finally, the challenges and future perspectives of artificial heart valve materials are discussed.

Both of the surface topographical features and distribution of biochemical cues can influence the cell-substrate interactions and thereby tissue regeneration in vivo. However, they have not been combined simultaneously onto a biodegradable scaffold to demonstrate the synergistic role so far. In this study, a proof-of-concept study is performed to prepare micropatterns and peptide gradient on the inner wall of a poly (D,L-lactide-co-caprolactone) (PLCL) guidance conduit and its advantages in regeneration of peripheral nerve in vivo. After linear ridges/grooves of 20/40 μm in width are created on the PLCL film, its surface is aminolyzed in a kinetically controlled manner to obtain the continuous gradient of amino groups, which are then transferred to CQAASIKVAV peptide density gradient via covalent coupling of glutaraldehyde. The Schwann cells are better aligned along with the stripes, and show a faster migration rate toward the region of higher peptide density. Implantation of the nerve guidance conduit made of the PLCL film having both the micropatterns and peptide gradient can significantly accelerate the regeneration of sciatic nerve in terms of rate, function recovery and microstructures, and reduction of fibrosis in muscle tissues. Moreover, this nerve conduit can also benefit the M2 polarization of macrophages and promote vascularization in vivo.

Biomedical microgels are a novel type of materials with promising perspectives for repair and regeneration of multi-types of tissues and organs due to their highly hydrated nature, tunable microporous structure, ability to encapsulate bioactive factors, and tailorable properties such as stiffness and composition. In particular, the reversible bonding in supramolecular microgels leads to their ease of injectability and self-healing ability, which are essential for therapeutic delivery of cells and drugs, assembly to generate scaffolds, and bioinks for 3D printing. In vivo studies of microgels have pioneered the clinical relevance of these novel and innovative materials for regenerative medicine. In this review, the important supramolecular interactions such as hydrogen bonding, ionic bonding, and host-guest and hydrophobic interactions, and metal coordination are summarized with respect to the formation of supramolecular microgels for biomedical applications, highlighting their advantages over the traditional bulk ones. The applications of supramolecular microgels in the fields of cardiac tissue repair, osteoarthritis therapy, and bone and neuronal tissue engineering are discussed.

Polyurethanes have been broadly used as biomaterials in tissue repair and regeneration due to their preeminent biocompatibility and mechanical properties. However, traditional polyurethanes are not able to efficiently cope with the complexity of dynamic tissue microenvironments during the process of disease therapy. Physiologically responsive polyurethanes responding or reacting to biological signals or pathological abnormalities can change their physicochemical properties, enabling on‐demand release or intelligently promoting tissue regeneration. So far, the physiologically responsive polyurethanes have gained significant interest for applications in controlled drug delivery systems and tissue engineering in recent years. This review highlights the research advances in the design of the physiological‐responsive polyurethanes and their applications for tissue repair and regeneration, with particular attention to some representative examples such as pH‐, redox‐, temperature‐, and enzyme‐responsive polyurethanes. The key design principles and applications are illustrated in the treatment of retinal detachment, gastric ulcer, wound, myocardial infarction, lung injury, bone defect, and osteoarthritis. The challenges and future perspectives of the physiological‐responsive polyurethanes are finally discussed.

Background: In this study, a new composite biological mesh named SFP was prepared by combining silk fibroin with polypropylene mesh. The mechanism and clinical application value of the SFP composite mesh were explored.Methods: The fibrous membrane was prepared by electrospinning of silk fibroin. The silk fibrous membrane was adhered to the polypropylene mesh by fibrin hydrogel to make a new composite mesh. The characterizations were verified by structural analysis and in vitro cell experiments. A total of 40 Sprague–Dawley rats were randomly divided into two groups, and 20 rats in each group were implanted with the SFP mesh and pure polypropylene mesh, respectively. The rats were sacrificed in batches on the 3rd, 7th, 14th, and 90th days after surgery. The adhesion degree and adhesion area on the mesh surface were compared, and a histopathological examination was carried out.Results:In vitro cell function experiments confirmed that the SFP mesh had good cell viability. The control group had different degrees of adhesion on the 3rd, 7th, 14th, and 90th days after surgery. However, there was almost no intraperitoneal adhesions on the 3rd and 7th days after surgery, and some rats only had mild adhesions on the 14th and 90th days after surgery in the SFP group. There were statistically significant differences in the postoperative intraperitoneal adhesion area and adhesion degree between the two groups (p < 0.05). Histopathological examination confirmed that the mesenchymal cells were well arranged and continuous, and there were more new capillaries and adipocyte proliferation under the mesenchymal cells in the SFP group.Conclusion: The SFP mesh shows good biocompatibility and biofunction in vitro and in vivo. It can promote the growth of peritoneal mesenchymal cells. The formation of a new mesenchymal cell layer can effectively reduce the extent and scope of adhesion between the mesh and abdominal organs. The SFP mesh will have a good application prospect in the field of abdominal wall hernia repair.

Spatial dimension of pores and interconnection in macroporous scaffolds is of particular importance in facilitating endogenous cell migration and bone tissue ingrowth. However, it is still a challenge to widely tune structure parameters of scaffolds by conventional methods because of inevitable pore geometrical deformation and poor pore interconnectivity. Here, the long-term in vivo biological performances of nonstoichiometric bioceramic scaffolds with different pore dimensions were assessed in critical-size femoral bone defect model. The 6% Mg-substituted wollastonite (CSi-Mg6) powders were prepared via wet-chemical precipitation and the scaffolds elaborately printed by ceramic stereolithography, displaying designed constant pore strut and tailorable pore height (200, 320, 450, 600 μm), were investigated thoroughly in the bone regeneration process. Together with detailed structural stability and mechanical properties were collaboratively outlined. Both μCT and histological analyses indicated that bone tissue ingrowth was retarded in 200 μm scaffolds in the whole stage (2–16 weeks) but the 320 μm scaffolds showed appreciable bone tissue in the center of porous constructs at 6–10 weeks and matured bone tissue were uniformly invaded in the whole pore networks at 16 weeks. Interestingly, the neo-tissue ingrowth was facilitated in the 450 μm and 600 μm scaffolds after 2 weeks and higher extent of bone regeneration and remodeling at the later stage. These new findings provide critical information on how engineered porous architecture impact bone regeneration in vivo. Simultaneously, this study shows important implications for optimizing the porous scaffolds design by advanced additive manufacture technique to match the clinical translation with high performance.

Hydrogels are three-dimensional platforms that serve as substitutes for native extracellular matrix. These materials are starting to play important roles in regenerative medicine because of their similarities to native matrix in water content and flexibility. It would be very advantagoues for researchers to be able to regulate cell behavior and fate with specific hydrogels that have tunable mechanical properties as biophysical cues. Recent developments in dynamic chemistry have yielded designs of adaptable hydrogels that mimic dynamic nature of extracellular matrix. The current review provides a comprehensive overview for adaptable hydrogel in regenerative medicine as follows. First, we outline strategies to design adaptable hydrogel network with reversible linkages according to previous findings in supramolecular chemistry and dynamic covalent chemistry. Next, we describe the mechanism of dynamic mechanical microenvironment influence cell behaviors and fate, including how stress relaxation influences on cell behavior and how mechanosignals regulate matrix remodeling. Finally, we highlight techniques such as bioprinting which utilize adaptable hydrogel in regenerative medicine. We conclude by discussing the limitations and challenges for adaptable hydrogel, and we present perspectives for future studies.

Thermal therapy has continued to attract the attention of researchers and clinicians due to its important applications in tumor ablation, wound management, and drug release. The lack of precise temperature control capability in traditional thermal treatment may cause the decrease of therapeutic effect and thermal damage to normal tissues. Here, we report an implantable thermal therapeutic device (ITTD), which offers precise closed loop heating, in situ temperature monitoring, and thermal protection. The ITTD features a multifunctional foldable electronics device wrapped on a heat-insulating composite pad. Experimental and numerical studies reveal the fundamental aspects of the design, fabrication, and operation of the ITTD. In vivo experiments of the ITTD in thermal ablation for antitumor demonstrate that the proposed ITTD is capable of controlling the ablation temperature precisely in real time with a precision of at least 0.7°C and providing effective thermal protection to normal tissues. This proof-of-concept research creates a promising route to develop ITTD with precise temperature control capability, which is highly desired in thermal therapy and other disease diagnosis and treatments.

Severe traction injuries after stretch to peripheral nerves are common and challenging to repair. The nerve guidance conduits (NGCs) are promising in the regeneration and functional recovery after nerve injuries. To enhance the repair of severe nerve traction injuries, in this study KHIFSDDSSE (KHI) peptides were grafted on a porous and micropatterned poly(D,L-lactide-co-caprolactone) (PLCL) film (MPLCL), which was further loaded with a nerve growth factor (NGF). The adhesion number of Schwann cells (SCs), ratio of length/width (L/W), and percentage of elongated SCs were significantly higher in the MPLCL-peptide group and MPLCL-peptide-NGF group compared with those in the PLCL group in vitro. The electromyography (EMG) and morphological changes of the nerve after severe traction injury were improved significantly in the MPLCL-peptide group and MPLCL-peptide-NGF group compared with those in the PLCL group in vivo. Hence, the NGCs featured with both bioactive factors (KHI peptides and NGF) and physical topography (parallelly linear micropatterns) have synergistic effect on nerve reinnervation after severe traction injuries.

Tissue regeneration is an active multiplex process involving the dynamic inflammatory microenvironment. Under a normal physiological framework, inflammation is necessary for the systematic immunity including tissue repair and regeneration as well as returning to homeostasis. Inflammatory cellular response and metabolic mechanisms play key roles in the well-orchestrated tissue regeneration. If this response is dysregulated, it becomes chronic, which in turn causes progressive fibrosis, improper repair, and autoimmune disorders, ultimately leading to organ failure and death. Therefore, understanding of the complex inflammatory multiple player responses and their cellular metabolisms facilitates the latest insights and brings novel therapeutic methods for early diseases and modern health challenges. This review discusses the recent advances in molecular interactions of immune cells, controlled shift of pro- to anti-inflammation, reparative inflammatory metabolisms in tissue regeneration, controlling of an unfavorable microenvironment, dysregulated inflammatory diseases, and emerging therapeutic strategies including the use of biomaterials, which expand therapeutic views and briefly denote important gaps that are still prevailing.

The delivery of nanomaterials or therapeutics into cells takes a decisive role for their applications in nanomedicine. Nature's creations such as viruses provide valued inspiration for design of nano-architectures in cellular delivery. We report herein the fabrication of biodegradable and biocompatible nanoparticles (NPs) with viral-mimicking morphology and constituents as a nanoplatform, which has rarely been reported to the best of our knowledge, for promoting cellular uptake and achieving high therapeutic efficiency in vivo. The chitosan-porphyrin-based NPs were endowed with a viral-imitating morphology through a novel pH-responsive decomposition-induced self-assembly method. By successive conjugation of Tat peptides and modification of lipids, morphological and constituent viral-mimicking NPs were obtained. Compared with the counterpart of non-viral-mimicking NPs, the viral-mimicking NPs showed prominent superiority in enhancing cell internalization (10 times higher). Loading of near-infrared photosensitizer– indocyanine green into these NPs demonstrated the striking capability of the viral-mimicking nanoparticles in therapeautic delivery and photothermal anti-tumor effect in vitro and in vivo. This concept and strategy provides an enlightening methodology on the design and fabrication of therapeutic delivery systems, which is significant for nanobiotechnology.

Tissue–biomaterial interactions in different microenvironments influence significantly the repair and regeneration outcomes when a scaffold or construct is implanted. In order to elucidate this issue, a fibrin gel filled macroporous fibrin scaffold (fibrin-based scaffold) was fabricated by loading fibrinogen via a negative pressure method, following with thrombin crosslinking. The macroporous fibrin scaffold exhibited a porous structure with porosity of (88.1 ± 1.3)%, and achieved a modulus of 19.8 ± 0.4 kPa at a wet state after fibrin gel filling, providing a suitable microenvironment for bone marrow-derived mesenchymal stem cells (BMSCs). The in vitro cellular culture revealed that the fibrin-based scaffold could support the adhesion, spreading, and proliferation of BMSCs in appropriate cell encapsulation concentrations. The fibrin-based scaffolds were then combined with BMSCs and lipofectamine/plasmid deoxyribonucleic acid (DNA) encoding mouse-transforming growth factor β1 (pDNA-TGF-β1) complexes to obtain the fibrin-based constructs, which were implanted into osteochondral and tibial defects at young adult rabbits (3 months old) and aged adult rabbits (12 months old) to evaluate their respective repair effects. Partial repair of osteochondral defects and perfect restoration of tibial defects were realized at 18 weeks post-surgery for the young adult rabbits, whereas only partial repair of subchondral bone and tibial bone defects were found at the same time for the aged adult rabbits, confirming the adaptability of the fibrin-based constructs to the different tissue microenvironments by tissue-biomaterial interplays.

Abstract As the most frequent wound complication, infection has become a major clinical challenge in wound management. To overcome the “Black Box” status of the wound‐healing process, next‐generation wound dressings with the abilities of real‐time monitoring, diagnosis during early stages, and on‐demand therapy has attracted considerable attention. Here, by combining the emerging development of bioelectronics, a smart flexible electronics‐integrated wound dressing with a double‐layer structure, the upper layer of which is polydimethylsiloxane‐encapsulated flexible electronics integrated with a temperature sensor and ultraviolet (UV) light‐emitting diodes, and the lower layer of which is a UV‐responsive antibacterial hydrogel, is designed. This dressing is expected to provide early infection diagnosis via real‐time wound‐temperature monitoring by the integrated sensor and on‐demand infection treatment by the release of antibiotics from the hydrogel by in situ UV irradiation. The integrated system possesses good flexibility, excellent compatibility, and high monitoring sensitivity and durability. Animal experiment results demonstrate that the integrated system is capable of monitoring wound status in real time, detecting bacterial infection and providing effective treatment on the basis of need. This proof‐of‐concept research holds great promise in developing new strategies to significantly improve wound management and other pathological diagnoses and treatments.

Cell migration plays a pivotal role in many pathological and physiological processes. So far, most of the studies have been focused on 2-dimensional cell adhesion and migration. Herein, the migration behaviors of cell spheroids in 3D hydrogels obtained by polymerization of methacrylated hyaluronic acid (HA-MA) and fibrinogen (Fg) with different ratios were studied. The Fg could be released to the medium gradually along with time prolongation, achieving the dynamic change of hydrogel structures and properties. Three types of cell spheroids, i.e., endothelial cell (EC), smooth muscle cell (SMC), and EC-SMC spheroids, were prepared with 10,000 cells in each, whose diameters were about 343, 108, and 224 μm, respectively. The composite hydrogels with an intermediate ratio of Fg allowed the fastest 3D migration of cell spheroids. The ECs-SMCs migrated longest up to 3200 μm at day 14, whereas the SMC spheroids migrated slowest with a distance of only ~400 μm at the same period of time. The addition of free RGD or anti-CD44 could significantly reduce the migration distance, revealing that the cell-substrate interactions take the major roles and the migration is mesenchymal dependent. Moreover, addition of anti-N-cadherin and MMP inhibitors also slowed down the migration rate, demonstrating that the degradation of hydrogels and cell-cell interactions are also largely involved in the cell migration. RT-PCR measurement showed that expression of genes related to cell adhesion and antiapoptosis, and angiogenesis was all upregulated in the EC-SMC spheroids than single EC or SMC spheroids, suggesting that the use of composite cell spheroids is more promising to promote cell-substrate interactions and maintenance of cell functions.

It is challenging to design photosensitizers (PS) with high quantum yields generating singlet oxygen due to severe aggregation between the hydrophobic PSs. Here they develop organoplatinum(II) metallatocage-based PS to overcome these challenges and show excellent antitumor effect.

Cancer chemotherapy can be hindered by drug resistance which leads to lower drug efficiency. Here, we have developed a drug delivery system that tethers doxorubicin to the surface of gold nanorods via a pH-sensitive linkage (AuNRs@DOX), for a combined photothermal and chemical therapy for cancer. First, AuNRs@DOX is ingested by HepG2 liver cancer cells. After endocytosis, the acidic pH triggers the release of doxorubicin, which leads to chemotherapeutic effects. The gold nanorods are not only carriers of DOX, but also photothermal conversion agents. In the presence of an 808 nm near-infrared laser, AuNRs@DOX significantly enhance the cytotoxicity of doxorubicin via the photothermal effect, which induces elevated apoptosis of hepG2 cancer cells, leading to better therapeutic effects in vitro and in vivo. Keywords: Gold nanorods, Doxorubicin, pH responsive, Photothermal therapy, Combinational therapy

Multifunctional nanomedicine platforms are highly promising for anticancer therapy. Here, the authors design polyrotaxane-based theranostic nanoparticles that combine targeted drug delivery with photothermal behaviour to exhibit potent anti-tumour effects in vivo.

Hyaluronic acid (HA)-based hydrogels have applied widely for biomedical applications due to its biocompatibility and biodegradability. However, the use of initiators or crosslinkers during the hydrogel formation may cause cytotoxicity and thereby impair the biocompatibility. Inspired by the crosslinking mechanism of fibrin gel, a novel HA-based hydrogel was developed via the in situ supramolecular assembly based on knob-hole interactions between fibrinogen and knob-grafted HA (knob-g-HA) in this study. The knob-grafted HA was synthesized by coupling knob peptides (GPRPAAC, a mimic peptide of fibrin knob A) to HA via Michael addition. Then the translucent fibrinogen/knob-g-HA hydrogels were prepared by simply mixing the solutions of knob-g-HA and fibrinogen at the knob/hole ratio of 1.2. The rheological behaviors of the fibrinogen/knob-g-HA hydrogels with the fibrinogen concentrations of 50, 100 and 200 mg/mL were evaluated, and it was found that the dynamic storage moduli (G′) were higher than the loss moduli (G″) over the whole frequency range for all the groups. The SEM results showed that fibrinogen/knob-g-HA hydrogels presented the heterogeneous mesh-like structures which were different from the honeycomb-like structures of fibrinogen/MA-HA hydrogels. Correspondingly, a higher swelling ratio was obtained in the groups of fibrinogen/knob-g-HA hydrogel. Finally, the cytocompatibility of fibrinogen/knob-g-HA hydrogels was proved by live/dead stainings and MTT assays in the 293T cells encapsulation test. All these results highlight the biological potential of the fibrinogen/knob-g-HA hydrogels for 3D cellular engineering.