Advanced Healthcare Materials最新文献

Current treatments for osteoarthritis (OA) often fail to address the underlying pathophysiology and may have systemic side effects, particularly associated with long-term use of non-steroidal anti-inflammatory drugs (NSAIDs). Thus, researchers are currently directing their efforts toward innovative polymer-drug combinations, such as mixtures of hyaluronic acid viscoelastic hydrogels and NSAIDs like diclofenac, to ensure sustained release of the NSAID within the joint following intra-articular injection. However, the progress of novel injectable therapies for OA is hindered by the absence of preclinical models that accurately represent the pathology of the disease. The uBeat® MultiCompress platform is here presented as a novel approach for studying anti-OA injectable therapeutics on human mechanically-damaged OA cartilage microtissues, in a physiologically relevant environment. This platform can accommodate injectable therapeutic formulations and is successfully tested with SYN321, a novel diclofenac-sodium hyaluronate conjugate under development as a treatment for knee OA. Results indicate the platform's effectiveness in evaluating therapeutic potential, showing downregulation of inflammatory markers and reduction in matrix degradation in OA cartilage micro-tissues treated with SYN321. The uBeat® MultiCompress platform thus represents a valuable tool for OA research, offering a bridge between traditional in vitro studies and potential clinical applications, with implications for future drug discovery.

Organ Neuroprosthetics

Implantable neural interfaces can be used to (re-)establish the connection between new (transplanted or artificial) organs and the nervous system to increase the effective biointegration of these solutions. These “organ neuroprostheses” will become more and more valuable solutions in the years to come. The cover of article 2302896 by Silvestro Micera and co-workers show the possible use of nerve guidance channels to connect vagus nerve after heart transplantation. Cover design by Alessio Tommasetti.

Microelectrodes

While microfabrication has revolutionized the in vivo recording of neuronal activity, the ideal electrical transfer characteristics of electrodes are still debated. In article 2303401, Maria Asplund and co-workers show that lowering the electrode impedance consistently results in higher signal amplitude and unit yield. Using chronically implanted flexible arrays and comparing four different electrode materials they were able to confirm that recording quality increases as impedance decreases. Image credit: Eli Krantz, Krantz NanoArt.

Wireless Nanoscale Neurostimulators

Nanoelectrodes made of magnetoelectric materials enable remotely powered neurostimulation. Magnetic carrier signals are converted into an electric neuromodulatory signal, and thus stimulate native tissue. In article 2302871, Prachi Kumari, Kristen Kozielski, and co-workers demonstrate a generalizable and accessible method for evaluating the stimulation capability of these nanoelectrodes, and validate this method with experimental in vivo data, to facilitate their realization as minimally-invasive neural devices.

Osteoarthritis (OA) of the knee is the most prevalent degenerative joint condition that places a substantial financial and medical burden on society. However, due to drawbacks such as inefficiency, adverse effects, and brief duration of action, the clinical efficacy of the current major therapies for knee OA is largely restricted. Therefore, novel medication development is highly required to address these issues. Numerous studies in recent years have established that nanomaterials can be a potential and highly effective way to overcome these challenges. In this review, the anatomical distinctions between healthy and OA knee joints, as well as novel advances in the field of nanomaterials for the treatment of knee OA are summarized. The limits of the present therapeutic strategies for treating knee OA are also highlighted, as well as the potential prospects of nanomaterials in the future.

Gaining spatial control over innate immune activation is of great relevance during vaccine delivery and anticancer therapy, where one aims at activating immune cells at draining lymphoid tissue while avoiding systemic off-target innate immune activation. Lipid-polymer amphiphiles show high tendency to drain to lymphoid tissue upon local administration. Here, pH-sensitive, cholesteryl end group functionalized polymers as stimuli-responsive carriers are introduced for controlled immunoactivation of draining lymph nodes. Methacrylamide-based monomers bearing pendant 2-propionic-3-methylmaleic anhydride groups are polymerized by Reversible Addition-Fragmentation Chain Transfer (RAFT) polymerization using a cholesterol chain-transfer agent (chol-CTA). The amine-reactive anhydrides are conjugated with various amines, however, while primary amines afforded irreversible imides, secondary amines provided pH-responsive conjugates that are released upon acidification. This can be applied to fluorescent dyes for irreversibly carrier labeling or immunostimulatory Toll-like receptor (TLR) 7/8 agonists as cargos for pH-responsive delivery. Hydrophilization of remaining anhydride repeating units with short PEG-chains yielded cholesteryl-polymer amphiphiles that showed efficient cellular uptake and increased drug release at endosomal pH. Moreover, reversibly conjugated TLR 7/8 agonist amphiphiles efficiently drained to lymph nodes and increased the number of effectively maturated antigen-presenting cells after subcutaneous injection in vivo. Consequently, cholesteryl-linked methacrylamide-based polymers with pH-sensitive 2-propionic-3-methylmaleic anhydride side groups provide ideal features for immunodrug delivery.

The muscle-tendon junction (MTJ) plays a pivotal role in efficiently converting the muscular contraction into a controlled skeletal movement through the tendon. Given its complex biomechanical intricacy, the biofabrication of such tissue interface represents a significant challenge in the field of musculoskeletal tissue engineering. Herein, a novel method to produce MTJ-like hydrogel yarns using a microfluidics-assisted 3D rotary wet-spinning strategy is developed. Optimization of flow rates, rotational speed, and delivery time of bioinks enables the production of highly compartmentalized scaffolds that recapitulate the muscle, tendon, and the transient MTJ-like region. Additionally, such biofabrication parameters are validated in terms of cellular response by promoting an optimal uniaxial alignment for both muscle and tendon precursor cells. By sequentially wet-spinning C2C12 myoblasts and NIH 3T3 fibroblasts, a gradient-patterned cellular arrangement mirroring the intrinsic biological heterogeneity of the MTJ is successfully obtained. The immunofluorescence assessment further reveals the localized expression of tissue-specific markers, including myosin heavy chain and collagen type I/III, which demonstrate muscle and tenogenic tissue maturation, respectively. Remarkably, the muscle-tendon transition zone exhibits finger-like projection of the multinucleated myotubes in the tenogenic compartment, epitomizing the MTJ signature architecture.