Human platelet lysate-cultured adipose-derived stem cell sheets promote angiogenesis and accelerate wound healing via CCL5 modulation.

BACKGROUND: A rising population faces challenges with healing-impaired cutaneous wounds, often leading to physical disabilities. Adipose-derived stem cells (ASCs), specifically in the cell sheet format, have emerged as a promising remedy for impaired wound healing. Human platelet lysate (HPL) provides an attractive alternative to fetal bovine serum (FBS) for culturing clinical-grade ASCs. However, the potential of HPL sheets in promoting wound healing has not been fully investigated. This study aimed to explore the anti-fibrotic and pro-angiogenic capabilities of HPL-cultured ASC sheets and delve into the molecular mechanism. METHODS: A rat burn model was utilized to evaluate the efficacy of HPL-cultured ASC sheets in promoting wound healing. ASC sheets were fabricated with HPL, and those with FBS were included for comparison. Various analyses were conducted to assess the impact of HPL sheets on wound healing. Histological examination of wound tissues provided insights into aspects such as wound closure, collagen deposition, and overall tissue regeneration. Immunofluorescence was employed to assess the presence and distribution of transplanted ASCs after treatment. Further in vitro studies were conducted to decipher the specific factors in HPL sheets contributing to angiogenesis. RESULTS: HPL-cultured ASC sheets significantly accelerated wound closure, fostering ample and organized collagen deposition in the neo-dermis. Significantly more retained ASCs were observed in wound tissues treated with HPL sheets compared to the FBS counterparts. Moreover, HPL sheets mitigated macrophage recruitment and decreased subsequent wound tissue fibrosis in vivo. Immunohistochemistry also indicated enhanced angiogenesis in the HPL sheet group. The in vitro analyses showed upregulation of C-C motif chemokine ligand 5 (CCL5) and angiogenin in HPL sheets, including both gene expression and protein secretion. Culturing endothelial cells in the conditioned media compared to media supplemented with CCL5 or angiogenin suggested a correlation between CCL5 and the pro-angiogenic effect of HPL sheets. Additionally, through neutralizing antibody experiments, we further validated the crucial role of CCL5 in HPL sheet-mediated angiogenesis in vitro. CONCLUSIONS: The present study underscores CCL5 as an essential factor in the pro-angiogenic effect of HPL-cultured ASC sheets during the wound healing process. These findings highlight the potential of HPL-cultured ASC sheets as a promising therapeutic option for healing-impaired cutaneous wounds in clinical settings. Furthermore, the mechanism exploration yields valuable information for optimizing regenerative strategies with ASC products. BRIEF ACKNOWLEDGMENT: This research was supported by the National Science and Technology Council, Taiwan (NSTC112-2321-B-002-018), National Taiwan University Hospital (111C-007), and E-Da Hospital-National Taiwan University Hospital Joint Research Program (111-EDN0001, 112-EDN0002).

Biofunctionalized hydrogel composed of genipin-crosslinked gelatin/hyaluronic acid incorporated with lyophilized platelet-rich fibrin for segmental bone defect repair.

Segmental bone defects can arise from trauma, infection, metabolic bone disorders, or tumor removal. Hydrogels have gained attention in the field of bone regeneration due to their unique hydrophilic properties and the ability to customize their physical and chemical characteristics to serve as scaffolds and carriers for growth factors. However, the limited mechanical strength of hydrogels and the rapid release of active substances have hindered their clinical utility and therapeutic effectiveness. With ongoing advancements in material science, the development of injectable and biofunctionalized hydrogels holds great promise for addressing the challenges associated with segmental bone defects. In this study, we incorporated lyophilized platelet-rich fibrin (LPRF), which contains a multitude of growth factors, into a genipin-crosslinked gelatin/hyaluronic acid (GLT/HA-0.5 % GP) hydrogel to create an injectable and biofunctionalized composite material. Our findings demonstrate that this biofunctionalized hydrogel possesses optimal attributes for bone tissue engineering. Furthermore, results obtained from rabbit model with segmental tibial bone defects, indicate that the treatment with this biofunctionalized hydrogel resulted in increased new bone formation, as confirmed by imaging and histological analysis. From a translational perspective, this biofunctionalized hydrogel provides innovative and bioinspired capabilities that have the potential to enhance bone repair and regeneration in future clinical applications.

Effect of Sulfotyrosine and Negatively Charged Amino Acid of Leech-Derived Peptides on Binding and Inhibitory Activity Against Thrombin.

Hirudins, natural sulfo(glyco)proteins, are clinical anticoagulants that directly inhibit thrombin, a key coagulation factor. Their potent thrombin inhibition primarily results from antagonistic interactions with both the catalytic and non-catalytic sites of thrombin. Hirudins often feature sulfate moieties on Tyr residues in their anionic C-terminus region, enabling strong interactions with thrombin exosite-I and effectively blocking its engagement with fibrinogen. Although sulfotyrosines have been identified in various hirudin variants, the precise relationship between sulfotyrosine and the number of negatively charged amino acids within the anionic-rich C-terminus peptide domain for the binding of thrombin has remained elusive. By using Fmoc-SPPS, hirudin dodecapeptides homologous to the C-terminus of hirudin variants from various leech species were successfully synthesized, and the effect of sulfotyrosine and the number of negatively charged amino acids on hirudin-thrombin interactions was investigated. Our findings did not reveal any synergistic effect between an increasing number of sulfotyrosines or negatively charged amino acids and their inhibitory activity on thrombin or fibrinolysis in the assays, despite a higher binding level toward thrombin in the sulfated dodecapeptide Hnip_Hirudin was observed in SPR analysis.

Cold atmospheric plasma-enabled platelet vesicle incorporated iron oxide nano-propellers for thrombolysis.

A new approach to treating vascular blockages has been developed to overcome the limitations of current thrombolytic therapies. This approach involves biosafety and multimodal plasma-derived theranostic platelet vesicle incorporating iron oxide constructed nano-propellers platformed technology that possesses fluorescent and magnetic features and manifold thrombus targeting modes. The platform is capable of being guided and visualized remotely to specifically target thrombi, and it can be activated using near-infrared phototherapy along with an actuated magnet for magnetotherapy. In a murine model of thrombus lesion, this proposed multimodal approach showed an approximately 80 % reduction in thrombus residues. Moreover, the new strategy not only improves thrombolysis but also boosts the rate of lysis, making it a promising candidate for time-sensitive thrombolytic therapy.

Fortification of Iron Oxide as Sustainable Nanoparticles: An Amalgamation with Magnetic/Photo Responsive Cancer Therapies.

Due to their non-toxic function in biological systems, Iron oxide NPs (IO-NPs) are very attractive in biomedical applications. The magnetic properties of IO-NPs enable a variety of biomedical applications. We evaluated the usage of IO-NPs for anticancer effects. This paper lists the applications of IO-NPs in general and the clinical targeting of IO-NPs. The application of IONPs along with photothermal therapy (PTT), photodynamic therapy (PDT), and magnetic hyperthermia therapy (MHT) is highlighted in this review's explanation for cancer treatment strategies. The review's study shows that IO-NPs play a beneficial role in biological activity because of their biocompatibility, biodegradability, simplicity of production, and hybrid NPs forms with IO-NPs. In this review, we have briefly discussed cancer therapy and hyperthermia and NPs used in PTT, PDT, and MHT. IO-NPs have a particular effect on cancer therapy when combined with PTT, PDT, and MHT were the key topics of the review and were covered in depth. The IO-NPs formulations may be uniquely specialized in cancer treatments with PTT, PDT, and MHT, according to this review investigation.

Expanding applications of allogeneic platelets, platelet lysates, and platelet extracellular vesicles in cell therapy, regenerative medicine, and targeted drug delivery.

Platelets are small anucleated blood cells primarily known for their vital hemostatic role. Allogeneic platelet concentrates (PCs) collected from healthy donors are an essential cellular product transfused by hospitals to control or prevent bleeding in patients affected by thrombocytopenia or platelet dysfunctions. Platelets fulfill additional essential functions in innate and adaptive immunity and inflammation, as well as in wound-healing and tissue-repair mechanisms. Platelets contain mitochondria, lysosomes, dense granules, and alpha-granules, which collectively are a remarkable reservoir of multiple trophic factors, enzymes, and signaling molecules. In addition, platelets are prone to release in the blood circulation a unique set of extracellular vesicles (p-EVs), which carry a rich biomolecular cargo influential in cell-cell communications. The exceptional functional roles played by platelets and p-EVs explain the recent interest in exploring the use of allogeneic PCs as source material to develop new biotherapies that could address needs in cell therapy, regenerative medicine, and targeted drug delivery. Pooled human platelet lysates (HPLs) can be produced from allogeneic PCs that have reached their expiration date and are no longer suitable for transfusion but remain valuable source materials for other applications. These HPLs can substitute for fetal bovine serum as a clinical grade xeno-free supplement of growth media used in the in vitro expansion of human cells for transplantation purposes. The use of expired allogeneic platelet concentrates has opened the way for small-pool or large-pool allogeneic HPLs and HPL-derived p-EVs as biotherapy for ocular surface disorders, wound care and, potentially, neurodegenerative diseases, osteoarthritis, and others. Additionally, allogeneic platelets are now seen as a readily available source of cells and EVs that can be exploited for targeted drug delivery vehicles. This article aims to offer an in-depth update on emerging translational applications of allogeneic platelet biotherapies while also highlighting their advantages and limitations as a clinical modality in regenerative medicine and cell therapies.

P-Selectin mediates targeting of a self-assembling phototherapeutic nanovehicle enclosing dipyridamole for managing thromboses.

Thrombotic vascular disorders, specifically thromboembolisms, have a significant detrimental effect on public health. Despite the numerous thrombolytic and antithrombotic drugs available, their efficacy in penetrating thrombus formations is limited, and they carry a high risk of promoting bleeding. Consequently, the current medication dosage protocols are inadequate for preventing thrombus formation, and higher doses are necessary to achieve sufficient prevention. By integrating phototherapy with antithrombotic therapy, this study addresses difficulties related to thrombus-targeted drug delivery. We developed self-assembling nanoparticles (NPs) through the optimization of a co-assembly engineering process. These NPs, called DIP-FU-PPy NPs, consist of polypyrrole (PPy), dipyridamole (DIP), and P-selectin-targeted fucoidan (FU) and are designed to be delivered directly to thrombi. DIP-FU-PPy NPs are proposed to offer various potentials, encompassing drug-loading capability, targeted accumulation in thrombus sites, near-infrared (NIR) photothermal-enhanced thrombus management with therapeutic efficacy, and prevention of rethrombosis. As predicted, DIP-FU-PPy NPs prevented thrombus recurrence and emitted visible fluorescence signals during thrombus clot penetration with no adverse effects. Our co-delivery nano-platform is a simple and versatile solution for NIR-phototherapeutic multimodal thrombus control.

A Biomimicking and Multiarm Self-Indicating Nanoassembly for Site-Specific Photothermal-Potentiated Thrombolysis Assessed in Microfluidic and In Vivo Models.

Thrombolytic and antithrombotic therapies are limited by short circulation time and the risk of off-target hemorrhage. Integrating a thrombus-homing strategy with photothermal therapy are proposed to address these limitations. Using glycol chitosan, polypyrrole, iron oxide and heparin, biomimicking GCPIH nanoparticles are developed for targeted thrombus delivery and thrombolysis. The nanoassembly achieves precise delivery of polypyrrole, exhibiting biocompatibility, selective accumulation at multiple thrombus sites, and enhanced thrombolysis through photothermal activation. To simulate targeted thrombolysis, a microfluidic model predicting thrombolysis dynamics in realistic pathological scenarios is designed. Human blood assessments validate the precise homing of GCPIH nanoparticles to activated thrombus microenvironments. Efficient near-infrared phototherapeutic effects are demonstrated at thrombus lesions under physiological flow conditions ex vivo. The combined investigations provide compelling evidence supporting the potential of GCPIH nanoparticles for effective thrombus therapy. The microfluidic model also offers a platform for advanced thrombolytic nanomedicine development.

Cancer-targeted fucoidan­iron oxide nanoparticles for synergistic chemotherapy/chemodynamic theranostics through amplification of P-selectin and oxidative stress.

A combination of chemotherapy and chemodynamic therapy (CDT) is being developed to improve the theranostic efficacy and biological safety of current therapies. However, most CDT agents are restricted due to complex issues such as multiple components, low colloidal stability, carrier-associated toxicity, insufficient reactive oxygen species generation, and poor targeting efficacy. To overcome these problems, a novel nanoplatform composed of fucoidan (Fu) and iron oxide (IO) nanoparticles (NPs) was developed to achieve chemotherapy combined with CDT synergistic treatment with a facile self-assembling manner, and the NPs were made up of Fu and IO, in which the Fu was not only used as a potential chemotherapeutic but was also designed to stabilize the IO and target P-selectin-overexpressing lung cancer cells, thereby producing oxidative stress and thus synergizing the CDT efficacy. The Fu-IO NPs exhibited a suitable diameter below 300 nm, which favored their cellular uptake by cancer cells. Microscopic and MRI data confirmed the lung cancer cellular uptake of the NPs due to active Fu targeting. Moreover, Fu-IO NPs induced efficient apoptosis of lung cancer cells, and thus offer significant anti-cancer functions by potential chemotherapeutic-CDT.

Anticancer polypyrrole-polyethylenimine drug-free nanozyme for precise B-cell lymphoma therapy.

As an alternative strategy for cancer treatment, the combination of cancer nanomedicine and immunotherapy is promising with regard to efficacy and safety; however, precise modulation of the activation of antitumor immunity remains challenging. Therefore, the aim of the present study was to describe an intelligent nanocomposite polymer immunomodulator, drug-free polypyrrole-polyethyleneimine nanozyme (PPY-PEI NZ), which responds to the B-cell lymphoma tumor microenvironment, for precision cancer immunotherapy. Earlier engulfment of PPY-PEI NZs in an endocytosis-dependent manner resulted in rapid binding in four different types of B-cell lymphoma cells. The PPY-PEI NZ effectively suppressed B cell colony-like growth in vitro accompanied by cytotoxicity via apoptosis induction. During PPY-PEI NZ-induced cell death, mitochondrial swelling, loss of mitochondrial transmembrane potential (MTP), downregulation of antiapoptotic proteins, and caspase-dependent apoptosis were observed. Deregulated AKT and ERK signaling contributed to glycogen synthase kinase-3-regulated cell apoptosis following deregulation of Mcl-1 and MTP loss. Additionally, PPY-PEI NZs induced lysosomal membrane permeabilization while inhibiting endosomal acidification, partly protecting cells from lysosomal apoptosis. PPY-PEI NZs selectively bound and eliminated exogenous malignant B cells in a mixed culture system with healthy leukocytes ex vivo. While PPY-PEI NZs showed no cytotoxicity in wild-type mice, they provided long-term and efficient inhibition of the growth of B-cell lymphoma-driven nodules in a subcutaneous xenograft model. This study explores a potential PPY-PEI NZ-based anticancer agent against B-cell lymphoma.

Molecularly Targeted Photothermal Ablation of Epidermal Growth Factor Receptor-Expressing Cancer Cells with a Polypyrrole-Iron Oxide-Afatinib Nanocomposite.

Near-infrared-photothermal therapy (NIR-PTT) is a potential modality for cancer treatment. Directing photothermal effects specifically to cancer cells may enhance the therapeutic index for the best treatment outcome. While epithelial growth factor receptor (EGFR) is commonly overexpressed/genetically altered in human malignancy, it remains unknown whether targeting EGFR with tyrosine kinase inhibitor (TKI)-conjugated nanoparticles may direct NIR-PTT to cancers with cellular precision. In the present study, we tested this possibility through the fabrication of a polypyrrole-iron oxide-afatinib nanocomposite (PIA-NC). In the PIA-NC, a biocompatible and photothermally conductive polymer (polypyrrole) was conjugated to a TKI (afatinib) that binds to overexpressed wild-type EGFR without overt cytotoxicity. A Fenton catalyst (iron oxide) was further encapsulated in the NC to drive the intracellular ROS surge upon heat activation. Diverse physical and chemical characterization experiments were conducted. Particle internalization, cytotoxicity, ROS production, and apoptosis in EGFR-positive and -negative cell lines were investigated in the presence and absence of NIR. We found that the PIA-NCs were stable with a size of 243 nm and a zeta potential of +35 mV. These PIA-NCs were readily internalized close to the cell membrane by all types of cells used in the study. The Fourier transform infrared spectra showed 3295 cm-1 peaks; substantial O-H stretching was seen, with significant C=C stretching at 1637 cm-1; and a modest appearance of C-O-H bending at 1444 cm-1 confirmed the chemical conjugation of afatinib but not iron oxide to the NC. At a NIR-PTT energy level that has a minimal cytotoxic effect, PIA-NC significantly sensitizes EGFR-overexpressing A549 lung cancer cells to NIR-PTT-induced cytotoxicity at a rate of 70%, but in EGFR-negative 3T3 fibroblasts the rate was 30%. Within 1 min of NIR-PTT, a surge of intracellular ROS was found in PIA-NC-treated A549 cells. This was followed by early induction of cellular apoptosis for 54 ± 0.081% of A549 cells. The number of viable cells was less than a quarter of a percent. Viability levels of A549 cells that had been treated with NIR or PIA were only 50 ± 0.216% and 80 ± 0.216%, respectively. Only 10 ± 0.816% of NIH3T3 cells had undergone necrosis, meaning that 90 ± 0.124% were alive. Viability levels were 65 ± 0.081% and 81 ± 0.2%, respectively, when only NIR and PIA were used. PIA binding was effective against A549 cells but not against NIH3T3 cells. The outcome revealed that higher levels of NC + NIR exposure caused cancer cells to produce more ROS. In summary, our findings proved that a molecularly targeted NC provides an orchestrated platform for cancer cell-specific delivery of NIR-PTT. The geometric proximity design indicates a novel approach to minimizing the off-target biological effects of NIR-PTT. The potential of PIA-NC to be further developed into real-world application warrants further investigation.

Glycol chitosan/iron oxide/polypyrrole nanoclusters for precise chemodynamic/photothermal synergistic therapy.

Noninvasive photothermal therapy (PTT) represents a promising direction for more modern and precise medical applications. However, PTT efficacy is still not satisfactory due to the existence of heat shock proteins (HSPs) and poorly targeted delivery. Herein, the design of a nanosystem with improved delivery efficacy for anticancer treatment employing the synergetic effects of reactive oxygen species (ROS)-driven chemodynamic therapy (CDT) to inactivated HSPs with photothermal-hyperthermia was therefore achieved through the development of pH-targeting glycol chitosan/iron oxide enclosed core polypyrrole nanoclusters (GCPI NCs). The designed NCs effectively accumulated toward cancer cells due to their acidic microenvironment, initiating ROS generation via Fenton reaction at the outset and performing site-specific near infrared (NIR)-photothermal effect. A comprehensive analysis of both surface and bulk material properties of the CDT/PTT NCs as well as biointerface properties were ascertained via numerous surface specific analytical techniques by bringing together heightened accumulation of CDT/PTT NCs, which can significantly eradicate cancer cells thus minimizing the side effects of conventional chemotherapies. All of these attributes act in synergy over the cancer cells succeeding in fashioning NC's able to act as competent agents in the MRI-monitored enhanced CDT/PTT synergistic therapy. Findings in this study evoke attention in future oncological therapeutic strategies.

Cold atmospheric plasma physically reinforced substances of platelets-laden photothermal-responsive methylcellulose complex restores burn wounds.

Patients with irregular, huge burn wounds require time-consuming healing. The skin has an epithelial barrier mechanism. Hence, the penetration and retention of therapeutics across the skin to deep lesion is generally quite difficult and these usually constrain the delivery/therapeutic efficacies for wound healing. Effective burn wound healing also necessitates proper circulation. Conventional polymeric dressing usually exhibits weak mechanical behaviors, obstructing their load-bearing applications. Cold atmospheric plasma (CAP) was used as an efficient, environmentally friendly, and biocompatible process to crosslink methylcellulose (MC) designed for topical administration such as therapeutic substances of platelets (SP) and polyethyleneimine-polypyrrole nanoparticle (PEI-PPy NP)-laden MC hydrogel carriers, and wound dressings. The roles of framework parameters for CAP-treated SP-PEI-PPy NP-MC polymeric complex system; chemical, physical, and photothermal effects; morphological, spectroscopical, mechanical, rheological, and surface properties; in vitro drug release; and hydrophobicity are discussed. Furthermore, CAP-treated SP-PEI-PPy NP-MC polymeric complex possessed augmented mechanical properties, biocompatibility, sustainable drug release, drug-retention effects, and near-infrared (NIR)-induced hyperthermia effects that drove heat-shock protein (HSP) expression with drug permeation to deep lesions. This work sheds light on the CAP crosslinking polymeric technology and the efficacy of combining sustained drug release with photothermal therapy in burn wound bioengineering carrier designs.

Thrombus-specific theranostic nanocomposite for codelivery of thrombolytic drug, algae-derived anticoagulant and NIR fluorescent contrast agent.

Thrombolysis is a standard treatment for rapidly restoring blood flow. However, the application of urokinase-type plasminogen activator (Uk) in clinical therapy is limited due to its nonspecific distribution and inadequate therapeutic accumulation. Precise thrombus imaging and site-specific drug delivery can enhance the diagnostic and therapeutic efficacy for thrombosis. Accordingly, we developed a P-selectin-specific, photothermal theranostic nanocomposite for thrombus-targeted codelivery of Uk and indocyanine green (ICG, a contrast agent for near-infrared (NIR) fluorescence imaging). We evaluated its capabilities for thrombus imaging and enzyme/hyperthermia combined thrombolytic therapy. Mesoporous silica-coated gold nanorods (Si-AuNRs) were functionalized with an arginine-rich peptide to create an organic template for the adsorption of ICG and fucoidan (Fu), an algae-derived anticoagulant. Uk was loaded into the SiO2 pores of the Si-AuNRs through the formation of a Fu-Uk-ICG complex on the peptide-functionalized template. The Fu-Uk/ICG@SiAu NRs nanocomposite increased the photostability of ICG and improved its targeting/accumulation at blood clot sites with a strong NIR fluorescence intensity for precise thrombus imaging. Furthermore, ICG incorporated into the nanocomposite enhanced the photothermal effect of Si-AuNRs. Fu, as a P-selectin-targeting ligand, enabled the nanocomposite to target a thrombus site where platelets were activated. The nanocomposite enabled a faster release of Uk for rapid clearing of blood clots and a slower release of Fu for longer lasting prevention of thrombosis regeneration. The nanocomposite with multiple functions, including thrombus-targeting drug delivery, photothermal thrombolysis, and NIR fluorescence imaging, is thus an advanced theranostic platform for thrombolytic therapy with reduced hemorrhaging risk and enhanced imaging/thrombolysis efficiency. STATEMENT OF SIGNIFICANCE: Herein, for the first time, a P-selectin specific, photothermal theranostic nanocomposite for thrombus-targeted co-delivery of urokinase and NIR fluorescence contrast agent indocyanine green (ICG) was developed. We evaluated the potential of this theranostic nanocomposite for thrombus imaging and enzyme/hyperthermia combined thrombolytic therapy. The nanocomposite showed multiple functions including thrombus targeting and imaging, and photothermal thrombolysis. Besides, it allowed faster release of the thrombolytic urokinase for rapidly clearing blood clots and slower release of a brown algae-derived anticoagulant fucoidan (also acting as a P-selectin ligand) for prevention of thrombosis regeneration. The nanocomposite is thus a new and advanced theranostic platform for targeted thrombolytic therapy.

Keratin-Based Nanoparticles with Tumor-Targeting and Cascade Catalytic Capabilities for the Combinational Oxidation Phototherapy of Breast Cancer.

Photodynamic therapy (PDT) holds tantalizing prospects of a prominent cancer treatment strategy. However, its efficacy remains limited by virtue of the hypoxic tumor microenvironment and the inadequate tumor-targeted delivery of photosensitizers, and these can be further exacerbated by the lack of development of a well-controlled nitric oxide (NO) release system at the target site. Inspired by Chinese medicine, we propose a revealing new keratin application. Keratin has garnered attention as an NO generator; however, its oncological use has rarely been investigated. We hypothesized that the incorporation of a phenylboronic acid (PBA) targeting ligand/methylene blue (MB) photosensitizer with a keratin NO donor would facilitate precise tumor delivery, enhancing PDT. Herein, we demonstrated that MB@keratin/PBA/d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) nanoparticles (MB@KPTNPs) specifically targeted breast cancer cells and effectively suppressed their growth. Through MB-mediated biometabolism, the endocytic MB@KPTNPs produced a sufficient amount of intracellular NO that reduced the glutathione level while boosting the efficiency of PDT. A therapeutic combination of NO/PDT was therefore achieved, resulting in significant inhibition of both in vivo tumor growth and lung metastasis. These findings underscore the importance of utilizing keratin-based nanoparticles that simultaneously combine targeting of the tumor and self-generating NO with a cascading catalytic ability as a novel oxidation therapeutic strategy for enhancing PDT.

Bioactive Glass Fiber-Reinforced Plastic Composites Prompt a Crystallographic Lophelia Atoll-Like Skeletal Microarchitecture Actuating Periosteal Cambium.

The touchstone for bone replacing or anchoring trauma implants, besides resorption, includes functional ankylosis at a fixation point and replacement by viable functional neo-bone tissues. These parameters redefined the concept of "resorbability" as "bioresorbability." Interference screws are the most commonly used resorbable anchoring implants for anterior cruciate ligament (ACL) reconstruction (surgery). Over the years, the bioresorbable screw fixation armamentarium has amplified countless choices, but instability and postimplantation complications have raised concerns about its reliability and efficacy. Owing to this interest, in this work, bioactive glass fiber-reinforced plastic (BGFP) composites with (BGFPnb5) and without (BGFP5) niobicoxide composing multiplexed network modifiers are reported as bioresorbable bone-anchoring substitutes. These synergistically designed composites have a fabricated structure of continuous, unidirectional BG fibers reinforced in an epoxy resin matrix using "melt-drawing and microfabrication" technology. The BGFP microarchitecture is comprised of multiplexed oxide components that influence bioactive response in a distinctive lophelia atoll-like apatite formation. Furthermore, it assists in the proliferation, adherence, and migration of bone marrow-derived mesenchymal stem cells. It also exhibits superior physicochemical characteristics such as surface roughness, hydrophilic exposure, distinctive flexural strength, and bioresorption. Thus, it induces restorative bone osseointegration and osteoconduction and actuates periosteum function. In addition, the BGFP influences the reduction of DH5-α Escherichia coli in suspension culture, demonstrating potential antibacterial efficacy. In conclusion, the BGFP composite therapeutic efficacy demonstrates distinctive material characteristics aiding in bone regeneration and restoration that could serve as a pioneer in orthopedic regenerative medicine.

Dual-Targeting Glycol Chitosan/Heparin-Decorated Polypyrrole Nanoparticle for Augmented Photothermal Thrombolytic Therapy.

Near-infrared (NIR)-light-modulated photothermal thrombolysis has been investigated to overcome the hemorrhage danger posed by clinical clot-busting substances. A long-standing issue in thrombosis fibrinolytics is the lack of lesion-specific therapy, which should not be ignored. Herein, a novel thrombolysis therapy using photothermal disintegration of a fibrin clot was explored through dual-targeting glycol chitosan/heparin-decorated polypyrrole nanoparticles (GCS-PPY-H NPs) to enhance thrombus delivery and thrombolytic therapeutic efficacy. GCS-PPY-H NPs can target acidic/P-selectin high-expression inflammatory endothelial cells/thrombus sites for initiating lesion-site-specific thrombolysis by hyperthermia using NIR irradiation. A significant fibrin clot-clearance rate was achieved with thrombolysis using dual-targeting/modality photothermal clot disintegration in vivo. The molecular level mechanisms of the developed nanoformulations and interface properties were determined using multiple surface specific analytical techniques, such as particle size distribution, zeta potential, electron microscopy, Fourier-transform infrared spectroscopy (FTIR), wavelength absorbance, photothermal, immunofluorescence, and histology. Owing to the augmented thrombus delivery of GCS-PPY-H NPs and swift treatment time, dual-targeting photothermal clot disintegration as a systematic treatment using GCS-PPY-H NPs can be effectively applied in thrombolysis. This novel approach possesses a promising future for thrombolytic treatment.

Photothermal-Irradiated Polyethyleneimine-Polypyrrole Nanopigment Film-Coated Polyethylene Fabrics for Infrared-Inspired with Pathogenic Evaluation.

Influenza, pneumonia, and pathogenic infection of the respiratory system are boosted in cold environments. Low temperatures also result in vasoconstriction, restraint of blood flow, and decreased oxygen to the heart, and the risk of a heart attack would increase accordingly. The present face mask fabric fails to preserve its air-filtering function as its electrostatic function vanishes once exposed to water. Therefore, its filtering efficacy would be decreased meaningfully, making it nearly impracticable to reuse the disposable face masks. The urgent requirement for photothermal fabrics is also rising. Nanobased polyethyleneimine-polypyrrole nanopigments (NPP NPs) have been developed and have strong near-infrared spectrum absorption and exceptional photothermal convertible performance. Herein, the mask fabric used PE-fiber-constructed membrane (PEFM) was coated by the binding affinity of the cationic polyethyleneimine component of NPP NPs forming NPP NPs-PEFM. To the best of our knowledge, no study has investigated NPP NP-coated mask fabric to perform infrared red (solar or body) photothermal conversion efficacy to provide biocompatible warming, remotely photothermally captured antipathogen, and antivasoconstriction in vivo. This pioneering study showed that the developed NPP NPs-PEFM could be washable, reusable, breathable, biocompatible, and photothermal conversable for active eradication of pathogenic bacteria. Further, it possesses warming preservation and antivasoconstriction.

Enhanced anticancer effect of ROS-boosted photothermal therapy by using fucoidan-coated polypyrrole nanoparticles.

Nanomaterial mediated cancer/tumor photo driven hyperthermia has obtained great awareness. Nevertheless, it is a challenge for improving the hyperthermic efficacy lacking resistance to stimulated thermal stress. We thus developed a bioinspired nano-platform utilizing inclusion complexation between photosensitive polypyrrole (Ppy) nanoparticles (NP) and fucoidan (FU). This FU-Ppy NP proved to be an excellent P-selectin-mediated, lung cancer-cell/tumor targeting delivery and specific accumulation, could augment cancer/tumor oxidative stress levels through producing cellular reactive oxygen species. Potent ROS/photothermal combinational therapeutic effects were exhibited by the bioinspired FU-Ppy NP through a selective P-selectin cancer/tumor targeting aptitude for the lung cancer cells/tumor compared with other nano-formulations. The usage of FU-Ppy NP also involves the potential mechanism of suppressing the biological expression of tumor vascular endothelial growth factor (VEGF). This FU biological macromolecule-amplified photothermally therapeutic nano-platform has promising potential for future medical translation in eradicating numerous tumors.

Microplasma Cross-Linked Graphene Oxide-Gelatin Hydrogel for Cartilage Reconstructive Surgery.

Herein, we report the cartilage tissue engineering application of nanographene oxide (NGO)-reinforced gelatin hydrogel fabricated by utilizing a microplasma-assisted cross-linking method. NGO sheets with surface functionalities were introduced to enhance the mechanical and biomedical properties of gelatin-based hydrogels. Highly energetic reactive radicals were generated from the nonthermal plasma (NTP), which is used to facilitate the cross-linking and polymerization during the polymeric hydrogel fabrication. The NTP treatment substantially reinforced a small amount (1 wt %) of NGO into the gelatin hydrogel. Systematic material characterization thus shows that the fabricated hydrogel possessed unique properties such as moderate surface roughness and adhesiveness, suitable pores sizes, temperature-dependent viscoelasticity, and controllable degradability. In vitro studies demonstrated that the as-fabricated hydrogel exhibited excellent cell-material interactions with SW 1353 cells, bone marrow-derived mesenchymal stem cells, and a rat chondrocyte cell line, thereby exhibiting appropriate cytocompatibility for cartilage tissue engineering applications. Furthermore, an in vivo study indicated that the formation of a healthy hyaline cartilage after the microfracture was enhanced by the fabricated hydrogel implant, offering a potential biocompatible platform for microfracture-based cartilage reconstructive surgery.