Docosahexaenoic Acid-Infused Core-Shell Fibrous Membranes for Prevention of Epidural Adhesions.

Avoiding epidural adhesion following spinal surgery can reduce clinical discomfort and complications. As the severity of epidural adhesion is positively correlated with the inflammatory response, implanting a fibrous membrane after spinal surgery, which can act as a physical barrier to prevent adhesion formation while simultaneously modulates postoperative inflammation, is a promising approach to meet clinical needs. Toward this end, we fabricated an electrospun core-shell fibrous membrane (CSFM) based on polylactic acid (PLA) and infused the fiber core region with the potent natural anti-inflammatory compound docosahexaenoic acid (DHA).

Magnetic lipid-poly(lactic-co-glycolic acid) nanoparticles conjugated with epidermal growth factor receptor antibody for dual-targeted delivery of CPT-11.

To entrap sparingly water-soluble drugs like CPT-11 (irinotecan), the poly(lactic-co-glycolic acid) (PLGA) nanoparticle (NP) is highly favored due to its low cytotoxicity and approval for clinical use. On the other hand, entrapping hydrophobic oleic acid-coated iron oxide magnetic nanoparticles (OMNP) in PLGA NP can provide a nanovehicle for magnetically targeted drug delivery. Our goal in this study is to develop a new dual-targeted magnetic lipid-polymer NP for the delivery of CPT-11.

Composite Polycaprolactone/Gelatin Nanofiber Membrane Scaffolds for Mesothelial Cell Culture and Delivery in Mesothelium Repair.

To repair damaged mesothelium tissue, which lines internal organs and cavities, a tissue engineering approach with mesothelial cells seeded to a functional nanostructured scaffold is a promising approach. Therefore, this study explored the uses of electrospun nanofiber membrane scaffolds (NMSs) as scaffolds for mesothelial cell culture and transplantation. We fabricated a composite NMS through electrospinning by blending polycaprolactone (PCL) with gelatin.

Doxorubicin-Loaded Ultrasmall Gold Nanoparticles (1.5 nm) for Brain Tumor Therapy and Assessment of Their Biodistribution.

Ultrasmall gold nanoparticles (1.5 nm) were covalently conjugated with doxorubicin (AuDox) and AlexaFluor647 (AuAF647) to assess their biodistribution and their efficiency toward brain tumors (glioblastoma). A thorough characterization by transmission electron microscopy, small-angle X-ray scattering, and differential centrifugal sedimentation confirmed their uniform ultrasmall nature which makes them very mobile in the body.

Bone Tissue Engineering with Adipose-Derived Stem Cells in Polycaprolactone/Graphene Oxide/Dexamethasone 3D-Printed Scaffolds.

We fabricated three-dimensional (3D)-printed polycaprolactone (PCL) and PCL/graphene oxide (GO) (PGO) scaffolds for bone tissue engineering. An anti-inflammatory and pro-osteogenesis drug dexamethasone (DEX) was adsorbed onto GO and a 3D-printed PGO/DEX (PGOD) scaffold successfully improved drug delivery with a sustained release of DEX from the scaffold up to 1 month. The physicochemical properties of the PCL, PGO, and PGOD scaffolds were characterized by various analytical techniques.

Immunomodulatory R848-Loaded Anti-PD-L1-Conjugated Reduced Graphene Oxide Quantum Dots for Photothermal Immunotherapy of Glioblastoma.

Glioblastoma multiforme (GBM) is the most severe form of brain cancer and presents unique challenges to developing novel treatments due to its immunosuppressive milieu where receptors like programmed death ligand 1 (PD-L1) are frequently elevated to prevent an effective anti-tumor immune response. To potentially shift the GBM environment from being immunosuppressive to immune-enhancing, we engineered a novel nanovehicle from reduced graphene oxide quantum dot (rGOQD), which are loaded with the immunomodulatory drug resiquimod (R848) and conjugated with an anti-PD-L1 antibody (aPD-L1). The immunomodulatory rGOQD/R8/aPDL1 nanoparticles can actively target the PD-L1 on the surface of ALTS1C1 murine glioblastoma cells and release R848 to enhance the T-cell-driven anti-tumor response.

Targeted Thrombolysis with Magnetic Nanotherapeutics: A Translational Assessment.

Plasminogen activators, such as recombinant tissue-type plasminogen activators (rtPAs), while effective in treating thromboembolic diseases, often induce hemorrhagic complications due to non-specific enzyme activities in the systemic circulation. This study evaluated the targeting efficiency, efficacy, biodistribution, and potential toxicity of a rtPA covalently attached to chitosan-coated magnetic nanoparticles (chitosan-MNP-rtPA). The thrombolytic activity of a chitosan-MNP-rtPA was preserved by protection from an endogenous plasminogen activator inhibitor-1 (PAI-1) in whole blood and after circulation in vivo, as examined by thromboelastometry.

Enhancing Photothermal/Photodynamic Therapy for Glioblastoma by Tumor Hypoxia Alleviation and Heat Shock Protein Inhibition Using IR820-Conjugated Reduced Graphene Oxide Quantum Dots.

We use low-molecular-weight branched polyethylenimine (PEI) to produce cytocompatible reduced graphene oxide quantum dots (rGOQD) as a photothermal agent and covalently bind it with the photosensitizer IR-820. The rGOQD/IR820 shows high photothermal conversion efficiency and produces reactive oxygen species (ROS) after irradiation with near-infrared (NIR) light for photothermal/photodynamic therapy (PTT/PDT). To improve suspension stability, rGOQD/IR820 was PEGylated by anchoring with the DSPE hydrophobic tails in DSPE-PEG-Mal, leaving the maleimide (Mal) end group for covalent binding with manganese dioxide/bovine serum albumin (MnO/BSA) and targeting ligand cell-penetrating peptide (CPP) to synthesize rGOQD/IR820/MnO/CPP.

Chitosan-coated magnetic graphene oxide for targeted delivery of doxorubicin as a nanomedicine approach to treat glioblastoma.

In this study, magnetic graphene oxide (mGO) was first prepared and modified with chitosan to prepare chitosan-coated mGO (mGOC). Gastrin-releasing peptide (GRP)-conjugated mGOC (mGOCG) was then prepared from mGOC. The chemo drug doxorubicin (DOX) was adsorbed to mGOCG surface for dual active/magnetic targeted drug delivery.

Functionalized Nanomaterials for Inhibiting ATP-Dependent Heat Shock Proteins in Cancer Photothermal/Photodynamic Therapy and Combination Therapy.

Phototherapies induced by photoactive nanomaterials have inspired and accentuated the importance of nanomedicine in cancer therapy in recent years. During these light-activated cancer therapies, a nanoagent can produce heat and cytotoxic reactive oxygen species by absorption of light energy for photothermal therapy (PTT) and photodynamic therapy (PDT). However, PTT is limited by the self-protective nature of cells, with upregulated production of heat shock proteins (HSP) under mild hyperthermia, which also influences PDT.

Injectable Thermosensitive Hyaluronic Acid Hydrogels for Chondrocyte Delivery in Cartilage Tissue Engineering.

In this study, we synthesize a hyaluronic acid--poly(N-isopropylacrylamide) (HPN) copolymer by grafting the amine-terminated poly(N-isopropylacrylamide) (PNIPAM-NH) to hyaluronic acid (HA). The 5% PNIPAM-NH and HPN polymer solution is responsive to temperature changes with sol-to-gel phase transition temperatures around 32 °C. Compared with the PNIPAM-NH hydrogel, the HPN hydrogel shows higher water content and mechanical strength, as well as lower volume contraction, making it a better choice as a scaffold for chondrocyte delivery.

Injectable gelatin/glucosamine cryogel microbeads as scaffolds for chondrocyte delivery in cartilage tissue engineering.

In this study, we fabricate squeezable cryogel microbeads as injectable scaffolds for minimum invasive delivery of chondrocytes for cartilage tissue engineering applications. The microbeads with different glucosamine concentrations were prepared by combining the water-in-oil emulsion and cryogelation through crosslinking of gelatin with glutaraldehyde in the presence of glucosamine. The physicochemical characterization results show the successful preparation of cryogel microbeads with uniform shape and size, high porosity, large pore size, high water uptake capacity, and good injectability.

Cetuximab-Conjugated Magnetic Poly(Lactic-co-Glycolic Acid) Nanoparticles for Dual-Targeted Delivery of Irinotecan in Glioma Treatment.

A glioma is the most common malignant primary brain tumor in adults and is categorized according to its growth potential and aggressiveness. Within gliomas, grade 4 glioblastoma remains one of the most lethal malignant solid tumors, with a median survival time less than 18 months. By encapsulating CPT-11 and oleic acid-coated magnetic nanoparticles (OMNPs) in poly(lactic-co-glycolic acid) (PLGA) nanoparticles, we first prepared PLGA@OMNP@CPT-11 nanoparticles in this study.

Immunotherapeutic Approaches for the Treatment of Glioblastoma Multiforme: Mechanism and Clinical Applications.

Glioma is one of the most aggressive types of primary brain tumor with a high-grade glioma known as glioblastoma multiforme (GBM). Patients diagnosed with GBM usually have an overall survival rate of less than 18 months after conventional therapy. This bleak prognosis underlines the need to consider new therapeutic interventions for GBM treatment to overcome current treatment limitations.

Bioactive Nanostructured Scaffold-Based Approach for Tendon and Ligament Tissue Engineering.

An effective therapeutic strategy to treat tendon or ligament injury continues to be a clinical challenge due to the limited natural healing capacity of these tissues. Furthermore, the repaired tendons or ligaments usually possess inferior mechanical properties and impaired functions. Tissue engineering can restore the physiological functions of tissues using biomaterials, cells, and suitable biochemical signals.

Thermosensitive Cationic Magnetic Liposomes for Thermoresponsive Delivery of CPT-11 and SLP2 shRNA in Glioblastoma Treatment.

Thermosensitive cationic magnetic liposomes (TCMLs), prepared from dipalmitoylphosphatidylcholine (DPPC), cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)]-2000, and didodecyldimethylammonium bromide (DDAB) were used in this study for the controlled release of drug/gene for cancer treatment. After co-entrapping citric-acid-coated magnetic nanoparticles (MNPs) and the chemotherapeutic drug irinotecan (CPT-11) in the core of TCML (TCML@CPT-11), SLP2 shRNA plasmids were complexed with DDAB in the lipid bilayer to prepare TCML@CPT-11/shRNA with a 135.6 ± 2.

Enhancing Philtrum Morphology Using Fat Grafting Combined with Percutaneous Rigottomy in Repaired Unilateral Cleft Lip.

Background: Improving the philtrum morphology of patients with a secondary cleft lip deformity has been a challenge in cleft care. Combining fat grafting with percutaneous rigottomy has been advocated for treatment of volumetric deficiency associated with a scarred recipient site. This study assessed the outcome of synchronous fat grafting and rigottomy for improvement of cleft philtrum morphology.

Hyaluronic Acid-Modified Cisplatin-Encapsulated Poly(Lactic-co-Glycolic Acid) Magnetic Nanoparticles for Dual-Targeted NIR-Responsive Chemo-Photothermal Combination Cancer Therapy.

Combination chemo-photothermal therapy with nanomaterials can reduce the dose of chemotherapeutic drugs required for effective cancer treatment by minimizing toxic side effects while improving survival times. Toward this end, we prepare hyaluronic acid (HA)-modified poly(lactic-co-glycolic acid) (PLGA) magnetic nanoparticles (MNP) for the CD44 receptor-mediated and magnetic field-guided dual-targeted delivery of cisplatin (CDDP). By co-encapsulating the CDDP and oleic acid-coated iron oxide MNP (IOMNP) in PLGA, the PMNPc was first prepared in a single emulsification/solvent evaporation step and successively surface modified with chitosan and HA to prepare the HA/PMNPc.

Hyaluronic acid/platelet rich plasma-infused core-shell nanofiber membrane to prevent postoperative tendon adhesion and promote tendon healing.

An anti-adhesive barrier membrane incorporating hyaluronic acid (HA) can reduce fibroblasts attachment and impart lubrication effect for smooth tendon gliding during management of post-surgical tendon adhesion. On the other hand, as numerous growth factors are required during tendon recovery, growth factors released by platelets in platelet-rich plasma (PRP) can provide beneficial therapeutic effects to facilitate tendon recovery post tendon injury. Furthermore, PRP is reported to be associated with anti-inflammatory properties for suppressing postoperative adhesion.

PLGA/Gelatin/Hyaluronic Acid Fibrous Membrane Scaffold for Therapeutic Delivery of Adipose-Derived Stem Cells to Promote Wound Healing.

Hyaluronic acid (HA) has been suggested to be a preferential material for the delivery of adipose-derived stem cells (ASCs) in wound healing. By incorporating HA in electrospun poly (lactide-co-glycolide) (PLGA)/gelatin (PG) fibrous membrane scaffolds (FMS), we aim to fabricate PLGA/gelatin/HA (PGH) FMS to provide a milieu for 3D culture and delivery of ASCs. The prepared FMS shows adequate cytocompatibility and is suitable for attachment and growth of ASCs.

Polycaprolactone/Chitosan Composite Nanofiber Membrane as a Preferred Scaffold for the Culture of Mesothelial Cells and the Repair of Damaged Mesothelium.

Mesothelial cells are specific epithelial cells lining the serosal cavity and internal organs. Nonetheless, few studies have explored the possibility to culture mesothelial cells in a nanostructure scaffold for tissue engineering applications. Therefore, this study aims to fabricate nanofibers from a polycaprolactone (PCL) and PCL/chitosan (CS) blend by electrospinning, and to elucidate the effect of CS on the cellular response of mesothelial cells.

Development of high resilience spiral wound suture-embedded gelatin/PCL/heparin nanofiber membrane scaffolds for tendon tissue engineering.

This study develops a spiral wound scaffold based on gelatin/PCL/heparin (GPH) nanofiber membranes for tendon tissue engineering. By embedding sutures in dual layers of aligned GPH nanofiber membranes, prepared from mixed electrospinning of gelatin and PCL/heparin solutions, we fabricate a high resilience scaffold intended for the high loading environment experienced by tendons. The basic fibroblast growth factor (bFGF) was anchored to GPH scaffold through bioaffinity between heparin and bFGF, aim to provide biological cues for maintenance of tenogenic phenotype.

Functionalized Magnetic Nanoparticles for Alternating Magnetic Field- or Near Infrared Light-Induced Cancer Therapies.

The multi-faceted nature of functionalized magnetic nanoparticles (fMNPs) is well-suited for cancer therapy. These nanocomposites can also provide a multimodal platform for targeted cancer therapy due to their unique magnetic guidance characteristics. When induced by an alternating magnetic field (AMF), fMNPs can convert the magnetostatic energy to heat for magnetic hyperthermia (MHT), as well as for controlled drug release.

Hyaluronic acid-modified, IR780-conjugated and doxorubicin-loaded reduced graphene oxide for targeted cancer chemo/photothermal/photodynamic therapy.

We used reduced graphene oxide (rGO), which has two times higher photothermal conversion efficiency than graphene oxide (GO), as a photothermal agent for cancer photothermal therapy (PTT). By conjugating a photosensitizer IR780 to rGO, the IR780-rGO could be endowed with reactive oxygen species (ROSs) generation ability for concurrent photodynamic therapy (PDT). The IR780-rGO was coated with hyaluronic acid (HA) by electrostatic interaction to facilitate its intracellular uptake by U87 glioblastoma cells.

Photo-Crosslinked Hyaluronic Acid/Carboxymethyl Cellulose Composite Hydrogel as a Dural Substitute to Prevent Post-Surgical Adhesion.

A dural substitute is frequently used to repair dura mater during neurosurgical procedures. Although autologous or commercially available dural substitutes matched most of the requirements; difficulties during dural repair, including insufficient space for suturing, insufficient mechanical strength, easy tear and cerebrospinal fluid leakage, represent major challenges. To meet this need, a photo-crosslinked hydrogel was developed as a dural substitute/anti-adhesion barrier in this study, which can show sol-to-gel phase transition in situ upon short-time exposure to visible light.