Biomaterials Science最新文献

Inadequate vasculature poses a significant challenge in the clinical translation of tissue engineering constructs. Current strategies for vascularization typically recruit short-lived endothelial cells or induce mesenchymal stem cells (MSC) to differentiate into the endothelial lineage, often in combination with supporting pericytes or fibroblasts. However, endothelial-associated cocultures lack adaptive ability and form limited vasculature. In this study, we investigated the endothelial transdifferentiation of an MSC-fibroblast coculture loaded on a bioengineered graft and utilized the exosomes released by the coculture model as a biomarker to monitor the progress of vascularization inside the graft. To develop the pre-vascularized skin graft, dermal fibroblasts and MSC were seeded on a biocomposite chitosan/collagen/fibrinogen/D3 (CCF-D3) scaffold. The cocultured graft facilitated the differentiation of MSC to endothelial cells (MEnDoT). Additionally, it promoted vasculogenic sprouting through the VEGF–eNOS pathways, as evidenced by the expression of F-actin, VEGF-A, and downstream transcriptomic markers (CD31, CD34, eNOS, VEGF-A, VEGF-R2, PI3 K, and PLC-γ). Exosomes (∼130 nm diameter) were isolated from the coculture, and their spectral analysis revealed significant differences (p < 0.05) in the intensity ratio of nucleotides (952 cm⁻¹), polysaccharides (1071 cm⁻¹) and lipoproteins (1417 cm⁻¹), corresponding to vasculogenesis. The activation of the VEGF-associated pathway in the coculture model was validated using an inhibitor (dexamethasone), which was used to treat the coculture graft as a control. Thus, this study elucidated the vascularization of coculture constructs via the VEGF-associated pathway. It demonstrated the potential of exosome spectral fingerprints as promising biomarkers to monitor the vascularization progression inside the graft, paving the way for the development of standardized grafts for full-thickness skin tissue regeneration.

Currently, hormonal therapy for endometriosis faces challenges in achieving a balance between treatment and preserving the chance of pregnancy. Therefore, the development of non-hormonal therapy holds significant clinical importance. Angiogenesis is a hallmark of endometriosis, and anti-angiogenic therapies targeting the hypoxia-inducible factor-1α (HIF-1α) pathway are considered potential approaches for endometriosis. However, angiogenesis is also involved in numerous physiological processes, including pregnancy, and systemic anti-angiogenesis may lead to severe adverse effects. To address this, a cRGD-modified liposome nanodrug (cRGD-LP-ART) is synthesized, which enhances drug efficacy while reducing adverse reactions. Artesunate (ART), a non-hormonal drug used to treat malaria, has shown anti-angiogenic effects beyond its original indications in various benign and malignant diseases. With cRGD modification, cRGD-LP-ART can target ectopic lesions and inhibit local angiogenesis by suppressing the HIF-1α/vascular endothelial growth factor (VEGF) pathway. Furthermore, cRGD-LP-ART exhibits better therapeutic effects than free ART, without affecting ovarian function or causing atrophy of the eutopic endometrium, making it a promising new option for non-hormonal therapy of endometriosis. As a combination of liposomes and a clinically approved drug, cRGD-LP-ART holds great potential and clinical prospects for the treatment of endometriosis.

Accelerated rehabilitation following facial nerve injury presents unique clinical challenges. This study evaluates the therapeutic effects of concentrated growth factor (CGF) on facial nerve recovery in a rabbit model and on RSC96 Schwann cells. Characterization of the CGF membrane (CGFM) revealed a three-dimensional fibrin network with embedded platelets, and representative growth factors, including TGF-β1, PDGF-BB, IGF-1, bFGF, and VEGF, were detected. In vivo, the Crush + CGFM group exhibited enhanced axon and myelin regeneration, increased Schwann cell proliferation, and improved facial nerve function compared to the Crush group. In vitro, CGF treatment significantly promoted the proliferation and migration of RSC96 cells and facilitated axon elongation in NG108-15 cells compared to controls. Mechanistically, CGF treatment led to a significant increase in PDGFRβ phosphorylation. Inhibition of this pathway with SU16f decreased Schwann cell activity and hindered overall nerve rehabilitation. These results underscore CGF's potential to accelerate nerve repair by promoting axon and myelin regeneration and enhancing Schwann cell biological activity, with the PDGFRβ pathway playing a crucial regulatory role. This study highlights CGF as a promising therapeutic strategy for improving facial nerve rehabilitation.

Endosomal escape is a major bottleneck for efficient intracellular delivery of therapeutic cargoes, particularly for macromolecular biological cargoes such as peptides, proteins and nucleic acids. pH-responsive polymeric nanoparticles that can respond to changes in the pH of intracellular microenvironments have generated substantial interest in navigating the endosomal barrier. In this study, we applied the highly sensitive split luciferase endosomal escape quantification (SLEEQ) assay to better understand the endosomal escape efficiency of dual component pH-responsive nanoparticles based on poly(2-(diethylamino) ethyl methacrylate) (PDEAEMA) and poly(2-(diisopropylamino) ethyl methacrylate) (PDPAEMA). Previous work investigated the use of a disulfide-linked HiBiT peptide conjugate encapsulated within the nanoparticle core, which upon meeting the LgBiT protein in the cytosol demonstrated luminescence which could be quantified to assess endosomal escape. However, we were interested in understanding whether this assay could be tuned to understand the endosomal escape of both a therapeutic cargo and a larger carrier. To achieve this, we designed two different HiBiT conjugates by applying a carbonylacrylic-functionalized thioether (non-cleavable) linker, which is more stable in endosomes, and a less stable disulfide (cleavable) linker to attach HiBiT to the nanoparticle core. Nanoparticles with disulfide-linked HiBiT demonstrated a higher endosomal escape efficiency of 6–7%, whereas thioether-linked HiBiT demonstrated <3% endosomal escape efficiency with a twofold decrease in cytosolic delivery. This suggests that degradation of the disulfide linker in endosomes leads to cytosolic delivery of a free HiBiT cargo, while thioether-linked HiBiT polymers are larger and thus fewer HiBiT-carrier conjugates can escape the endosomes. Overall, this work demonstrates that the SLEEQ assay can be tuned to understand the cytosolic delivery of different components based on the use of different linker chemistries and thus it is an important tool for designing therapeutic delivery systems in the future.

Wound healing is a complex and dynamic process often accompanied by bacterial infection, inflammation, and excessive oxidative stress. Single-atom nanozymes with multi-enzymatic activities show significant potential for promoting the healing of infected wounds by modulating their antibacterial and anti-inflammatory properties in response to the wound's physiological environment. In this study, we synthesized MN₄ single-atom nanozymes with multi-enzymatic activities that intelligently respond to pH value changes in the wound healing process. In vitro experiments confirm their effectiveness against Gram-negative bacteria, attributed to elevated reactive oxygen species (ROS) accumulation within the bacterial cells. Moreover, a full-thickness skin wound-infected model demonstrates that MN₄ single-atom nanozymes accelerate wound repair and skin regeneration by suppressing the expression of tumor necrosis factor-alpha (TNF-α), promoting angiogenesis, and enhancing collagen deposition. In vivo biocompatibility experiments further demonstrate the favorable biocompatibility of these nanozymes, highlighting their potential for clinical applications in infected wound healing. These nanozymes respond intelligently to different microenvironments and may be suitable for addressing further complex and variable diseases.

Accurate imaging of tumor hypoxia in vivo is critical for early cancer diagnosis and clinical outcomes, highlighting the great need for its detection specificity and sensitivity. In this report, we propose a probe (HTRNP) that simultaneously has hypoxia-targeting and hypoxia-responsive capabilities to enhance the tumor hypoxia imaging efficiency. HTRNP was successfully prepared through the encapsulation of Pt(II)-tetrakis(pentafluorophenyl)porphyrin (PtPFPP), which exhibits hypoxia-dependent phosphorescence, within the amphiphilic block copolymer OPDMA-PF, which has hypoxia-targeting tertiary amine N-oxide moieties and hydrophobic perfluorobenzene ring structures, which highly improved the loading content and water solubility of PtPFPP. By combining targeting and response abilities toward hypoxic conditions, the HTRNP micelles efficiently accumulate in the tumor tissues and emit intense phosphorescence, thus enabling ultrasensitive detection of various tumor models, even of hundreds of cancer cells, indicating its promising potential for early cancer detection and phenotypic characterization.

Myoelectric biofeedback (EMG-BF) is a widely recognized and effective method for treating movement disorders caused by impaired nerve function. However, existing EMG-feedback devices are almost entirely located in large medical centers, which greatly limits patient accessibility. To address this critical limitation, there is an urgent need to develop a portable, cost-effective, and real-time monitoring device that can transcend the existing barriers to the treatment of EMG-BF. Our proposed solution leverages polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP) as core materials, ingeniously incorporating wood pulp nano celluloses (CNF-P)-Na⁺ to enhance the structural integrity. Additionally, the inclusion of nano-silica particles further augments the sensor's capabilities, enabling the creation of a stress-sensitive mineral ionization hydrogel sensor. This innovative approach not only capitalizes on the superior rheological properties of the materials but also, through advanced 3D printing technology, facilitates the production of a micro-scale structural hydrogel sensor with unparalleled sensitivity, stability, and durability. The potential of this sensor in the realm of human motion detection is nothing short of extraordinary. This development can potentially improve the treatment landscape for EMG-BF offering patients more convenient and efficient therapeutic options.

Photothermal treatment has attracted immense interest as a promising approach for biomedical applications such as cancer ablation, yet its effectiveness is often limited by insufficient laser penetration and challenges in achieving efficient targeting of photothermal agents. Here we developed a transvascular interventional photothermal therapy (Ti-PTT), which employed a small-sized microcatheter (outer diameter: 0.60 mm, 1.8 Fr) equipped with an ultrafine optical fiber (diameter: 100 μm) capable of simultaneously delivering photothermal agents while performing 808 nm laser irradiation via an endovascular route. Specifically, we employed two types of indocyanine green (ICG)-based photothermal agents, i.e. ICG solution serving as a purely photothermal agent and ICG-ethiodized oil (ICG–EO) emulsion acting as a radiopaque photothermal embolic agent. Using the customized microcatheter with the ICG solution, both proximal and distal embolization were able to be performed in a rat liver model. Compared to the ICG solution, the ICG–EO emulsion dramatically enhanced the ICG retention time, enabling a photothermally triggered precision vascular blockade to induce local embolization of large tissue volumes in a rat kidney model with an unfavorable ICG leakage rate. The Ti-PTT paves the way to broadening the potential applications of photothermal therapy through combination with clinical intervention-based approaches.

The treatment of corneal blindness due to corneal diseases and injuries often requires the transplantation of healthy cadaveric corneal endothelial graft tissue to restore corneal clarity and visual function. However, the limited availability of donor corneas poses a significant challenge in meeting the demand for corneal transplantation. As a result, there is a growing interest in developing strategies alleviate this unmet need, and one of the postulated approaches is to isolate and expand primary human corneal endothelial cells (HCECs) in vitro for use in cell therapy. This review summarizes the recent advancements in the expansion of HCECs using biomaterials. Two principal biomaterial-based approaches, including extracellular matrix (ECM) coating and functionalized synthetic polymers, have been investigated to create an optimal microenvironment for the expansion and maintenance of corneal endothelial cells (CECs). This review highlights the challenges and opportunities in expanding primary HCECs using biomaterials. It emphasizes the importance of optimizing biomaterial properties, cell culture conditions, and the roles of biophysical cues to achieve efficient expansion and functional maintenance of CECs. Biomaterial-based strategies hold significant promise for expanding primary HCECs and improving the outcomes of CEC transplantation. The integration of biomaterials as cell culture substrates and transplantable carriers offers a comprehensive approach to address the limitations associated with current corneal tissue engineering techniques.

We are facing a shortage of new antibiotics to fight against increasingly resistant bacteria. As an alternative to conventional small molecule antibiotics, antimicrobial polymers (AMPs) have great potential. These polymers contain cationic and hydrophobic groups and disrupt bacterial cell membranes through a combination of electrostatic and hydrophobic interactions. While most examples focus on ammonium-based cations, sulfonium groups are recently emerging to broaden the scope of polymeric therapeutics. Here, main-chain sulfonium polymers exhibit good antimicrobial activity. In contrast, the potential of side-chain sulfonium polymers remains less explored with structure–activity relationships still being limited. To address this limitation, we thoroughly investigated key factors influencing antimicrobial activity in side-chain sulfonium-based AMPs. For this, we combined sulfonium cations with different hydrophobic (aliphatic/aromatic) and hydrophilic polyethylene glycol (PEG) groups to create a library of polymers with comparable chain lengths. For all compositions, we additionally examined the position of cationic and hydrophobic groups on the polymer backbone, i.e., we systematically compared same center and different center structures. Bactericidal tests against Gram-positive and Gram-negative bacteria suggest that same center polymers are more active than different center polymers of similar clog P. Ultimately, sulfonium-based AMPs show superior bactericidal activity and selectivity when compared to their quaternary ammonium cationic analogues.