Biomaterials

The crosstalk between breast cancer cells and tumor associated macrophages (TAMs) greatly contributes to tumor progression and immunosuppression. In this work, cat eye syndrome chromosome region candidate 2 (CECR2) is identified to overexpress in breast cancer patients, which can recognize v-rel avian reticuloendotheliosis viral oncogene homolog A (RelA) and activate nuclear factor κB (NF-κB) to release colony stimulating factor-1 (CSF-1). Pharmacological inhibition of CECR2 by the bromodomain competitor (Bromosporine, Bro) can downregulate CSF-1 to inhibit M2 type TAMs...

Achieving sufficient bone regeneration in large segmental defects is challenging, with the structure of bone repair scaffolds and their loaded bioactive substances crucial for modulating the local osteogenic microenvironment. This study utilized digital laser processing (DLP)-based 3D printing technology to successfully fabricate high-precision methacryloylated polycaprolactone (PCLMA) bionic bone scaffold structures. Adipose-derived stem cell-engineered nanovesicles (ADSC-ENs) were uniformly and stably modified onto the bionic scaffold surface using a perfusion device, constructing a conducive microenvironment for tissue regeneration and long bone defect repair through the scaffold's structural design and the vesicles' biological functions...

Frequent injections of anti-CD124 monoclonal antibody (αCD124) over long periods of time are used to treat chronic rhinosinusitis with nasal polyps (CRSwNP). Needle-free, intranasal administration (i.n.) of αCD124 is expected to provide advantages of localized delivery, improved efficacy, and enhanced medication adherence. However, delivery barriers such as the mucus and epithelium in the nasal tissue impede penetration of αCD124. Herein, two novel protamine nanoconstructs: allyl glycidyl ether conjugated protamine (Nano-P) and polyamidoamine-linked protamine (Dendri-P) were synthesized and showed enhanced αCD124 penetration through multiple epithelial layers compared to protamine in mice...

Fungi infection is a serious threat to public health, but an effective antifungal strategy remains a challenge. Herein, a biomimetic nanocomposite with multifunctionalities, including fungi diagnosis, antifungal adhesion, precise fungi elimination, and cytokine sequestration, is constructed for battling Candida albicans (C. albicans) infection. By screening a range of cells, we find that the polarized macrophage cells have the strongest binding tendency toward C. albicans. Thus, their membranes were exfoliated to camouflage UCNPs and then decorated with photosensitizers (methylene blue, MB) and DNA sensing elements...

Lipid nanoparticles (LNPs) have recently emerged as successful gene delivery platforms for a diverse array of disease treatments. Efforts to optimize their design for common administration methods such as intravenous injection, intramuscular injection, or inhalation, revolve primarily around the addition of targeting ligands or the choice of ionizable lipid. Here, we employed a multi-step screening method to optimize the type of helper lipid and component ratios in a plasmid DNA (pDNA) LNP library to efficiently deliver pDNA through intraduodenal delivery as an indicative route for oral administration...

As bacterial keratitis progresses rapidly, prompt intervention is necessary. Current diagnostic processes are time-consuming and invasive, leading to improper antibiotics for treatment. Therefore, innovative strategies for diagnosing and treating bacterial keratitis are urgently needed. In this study, Cu2-x Se@BSA@NTRP nanoparticles were developed by loading nitroreductase-responsive probes (NTRPs) onto Cu2-x Se@BSA. These nanoparticles exhibited integrated fluorescence imaging and antibacterial capabilities...

Probiotic-based therapies have shown great potential in the prevention and treatment of many diseases by positively regulating intestinal flora homeostasis. However, the efficacy of oral probiotics is severely limited due to the loss of bioactivity, short intestinal retention time, and insufficient therapeutic effect. Here, based on droplet microfluidics, we developed a hydrogel microsphere with colonic targeting and mucoadhesive capabilities as a multifunctional delivery platform, which can be used for co-delivery of probiotics (Escherichia coli Nissle 1917, EcN) and auxiliary molecules (indole-3-propionic acid, IPA), achieving synergistic therapeutic effects...

Mesenchymal stem cell (MSC)-based therapy is an effective strategy for regenerative therapy. However, safety and ease of use are still issues to be overcome in clinical applications. Exosomes are naturally derived nanoparticles containing bioactive molecules, which serve as ideal cell-free therapeutic modalities. However, issues such as delivery, long-term preservation and activity maintenance of exosomes are other problems that limit their application. In this study, we proposed the use of rapid freeze-dry-thaw macroporous hydrogels for the encapsulation of HucMSC-derived exosomes (HucMSC-Exos) combined with an antimicrobial peptide coating...

Cells assemble fibronectin, the major extracellular matrix (ECM) protein, into fibrillar matrices, which serve as 3D architectural scaffolds to provide, together with other ECM proteins tissue-specific environments. Although recent approaches enable to bioengineer 3D fibrillar fibronectin matrices in vitro, it remains elusive how fibronectin can be co-assembled with other ECM proteins into complex 3D fibrillar matrices that recapitulate tissue-specific compositions and cellular responses. Here, we introduce the engineering of fibrillar fibronectin-templated 3D matrices that can be complemented with other ECM proteins, including vitronectin, collagen, and laminin to resemble ECM architectures observed in vivo...

Painful musculoskeletal disorders such as intervertebral disc (IVD) degeneration associated with chronic low back pain (termed "Discogenic back pain", DBP), are a significant socio-economic burden worldwide and contribute to the growing opioid crisis. Yet there are very few if any successful interventions that can restore the tissue's structure and function while also addressing the symptomatic pain. Here we have developed a novel non-viral gene therapy, using engineered extracellular vesicles (eEVs) to deliver the developmental transcription factor FOXF1 to the degenerated IVD in an in vivo model...

A vascular anastomosis is a critical surgical skill that involves connecting blood vessels. Traditional handsewn techniques can be challenging and resource intensive. To address these issues, we have developed a unique sutureless anastomotic device called Vaso-Lock. This intraluminal device connects free vascular ends using anchors to maintain traction and enable a rapid anastomosis. We tested the anastomotic capability of Vaso-Locks in a pig common carotid-internal jugular arteriovenous model. The use of Vaso-Lock allowed us to accomplish this procedure in less than 10 min, in contrast to the approximately 40 min required for a handsewn anastomosis...

Exosomes, as nanoscale extracellular vesicles (EVs), are secreted by all types of cells to facilitate intercellular communication in living organisms. After being taken up by neighboring or distant cells, exosomes can alter the expression levels of target genes in recipient cells and thereby affect their pathophysiological outcomes depending on payloads encapsulated therein. The functions and mechanisms of exosomes in cardiovascular diseases have attracted much attention in recent years and are thought to have cardioprotective and regenerative potential...

Sarcopenia, a prevalent muscle disease characterized by muscle mass and strength reduction, is associated with impaired skeletal muscle regeneration. However, the influence of the biomechanical properties of sarcopenic skeletal muscle on the efficiency of the myogenic program remains unclear. Herein, we established a mouse model of sarcopenia and observed a reduction in stiffness within the sarcopenic skeletal muscle in vivo. To investigate whether the biomechanical properties of skeletal muscle directly impact the myogenic program, we established an in vitro system to explore the intrinsic mechanism involving matrix stiffness control of myogenic differentiation...

Immune checkpoint blockade therapy represented by programmed cell death ligand 1 (PD-L1) inhibitor for advanced renal carcinoma with an objective response rate (ORR) in patients is less than 20%. It is attributed to abundant tumoral vasculature with abnormal structure limiting effector T cell infiltration and drug penetration. We propose a bispecific fibrous glue (BFG) to regulate tumor immune and vascular microenvironments simultaneously. The bispecific precursor glue peptide-1 (pre-GP1) can penetrate tumor tissue deeply and self-assemble into BFG in the presence of neuropilin-1 (NRP-1) and PD-L1...

Surface-enhanced Raman spectroscopy (SERS) nanotags have garnered much attention as promising bioimaging contrast agent with ultrahigh sensitivity, but their clinical translation faces challenges including biological and laser safety. As breast sentinel lymph node (SLN) imaging agents, SERS nanotags used by local injection and only accumulation in SLNs, which were removed during surgery, greatly reduce biological safety concerns. But their clinical translation lacks pilot demonstration on large animals close to humans...

The treatment of infected wounds poses a formidable challenge in clinical practice due to the detrimental effects of uncontrolled bacterial infection and excessive oxidative stress, resulting in prolonged inflammation and impaired wound healing. In this study, we presented a MXene@TiO2 (MT) nanosheets loaded composite hydrogel named as GA/OKGM/MT hydrogel, which was formed based on the Schiff base reaction between adipic dihydrazide modified gelatin (GA)and Oxidized Konjac Glucomannan (OKGM), as the wound dressing...

Patients with cystic fibrosis (CF) experience severe lung disease, including persistent infections, inflammation, and irreversible fibrotic remodeling of the airways. Although therapy with transmembrane conductance regulator (CFTR) protein modulators reached optimal results in terms of CFTR rescue, lung transplant remains the best line of care for patients in an advanced stage of CF. Indeed, chronic inflammation and tissue remodeling still represent stumbling blocks during treatment, and underlying mechanisms are still unclear...

Herein, we describe the 3'-sialyllactose-polyethyleneimine-chlorine e6 conjugate (3PC), meticulously engineered to effectively target Helicobacter bacteria (H. pylori) within the gastric environment. The composition of 3PC comprises polyethyleneimine, a cationic polymer, 3'-sialyllactose, which exhibits a specific binding affinity for H. pylori surface proteins, and a photosensitizer capable of generating oxygen radicals in response to specific wavelengths. The distinctive feature of 3PC lies in its capacity to enhance interaction with the anionic mucus layer facilitated by electrostatic forces...

Catechol-based biomaterials demonstrate biocompatibility, making them suitable for a wide range of therapeutic applications when integrated into various molecular frameworks. However, the development of orally available catechol-based biomaterials has been hindered by significant pH variations and complex interactions in the gastrointestinal (GI) tract. In this study, we introduce a novel catechol-modified bile acid (CMBA), which is synthesized by anchoring the FDA-approved drug, ursodeoxycholic acid to the neurotransmitter dopamine...

The availability of human cell-based models capturing molecular processes of cartilage degeneration can facilitate development of disease-modifying therapies for osteoarthritis [1], a currently unmet clinical need. Here, by imposing specific inflammatory challenges upon mesenchymal stromal cells at a defined stage of chondrogenesis, we engineered a human organotypic model which recapitulates main OA pathological traits such as chondrocyte hypertrophy, cartilage matrix mineralization, enhanced catabolism and mechanical stiffening...