Sustained Release Of Dexamethasone Research Articles

Intravitreal OZURDEX vs. Intravitreal Bevacizumab for Diabetic Macular Edema: A Comprehensive Review.

This comprehensive review examines the efficacy, safety, and implications of intravitreal OZURDEX and intravitreal bevacizumab in treating diabetic macular edema (DME). DME is a common complication of diabetes mellitus and a leading cause of vision loss. OZURDEX, through sustained release of dexamethasone, targets inflammation and vascular permeability, while bevacizumab inhibits vascular endothelial growth factor (VEGF), reducing angiogenesis. However, differences in safety profiles exist, with OZURDEX associated with an increased risk of intraocular pressure elevation and cataract formation and bevacizumab potentially carrying systemic risks. The choice between these treatments should be individualized, considering patient preferences, ocular and systemic comorbidities, and cost-effectiveness. Collaboration among healthcare providers is essential for the comprehensive management of DME. Future research should focus on long-term comparative studies, predictors of treatment response, and exploration of novel therapeutic targets to optimize treatment outcomes for patients with DME.

Nanoengineered oxygen-releasing polymeric scaffold with sustained release of dexamethasone for bone regeneration

Maintaining the continuous oxygen supply and proper cell growth before blood vessel ingrowth at the bone defect site are considerably significant issues in bone regeneration. Oxygen-producing scaffolds can supply oxygen and avoid hypoxia leading to expedited bone regeneration. Herein, first oxygen-producing calcium peroxide nanoparticles (CPO NPs) are synthesized, and subsequently, the various amounts of synthesized CPO NPs (0.1, 0.5, and 1 wt/v%) loaded in the scaffold composite, which is developed by simple physical blending of chitosan (CS) and polycaprolactone (PCL) polymers. To deliver the synergistic therapeutic effect, dexamethasone (DEX), known for its potential anti-inflammatory and osteogenic properties, is loaded into the nanocomposite scaffolds. The extensive physicochemical characterizations of nanocomposite scaffolds confirm the successful loading of CPO NPs, adequate porous morphology, pore size, hydrophilicity, and biodegradability. In vitro, biological studies support the antibacterial, hemocompatible, and cytocompatible (MG-63 and MC3T3-E1 cells) nature of the material when tested on respective cells. Field emission scanning electron microscopy and energy-dispersive x-ray spectroscopy confirm the successful biomineralization of the scaffolds. Scaffolds also exhibit the sustained release of DEX and efficient protein adsorption. This study revealed that a nanoengineered scaffold loaded with CPO NPs (PCL/CS/DEX/CPO 3) is a suitable candidate for bone tissue regeneration.

Anti-fibrotic and anti-stricture effects of biodegradable biliary stents braided with dexamethasone-impregnated sheath/core structured monofilaments

Endoscopic biliary stent insertion has been widely used for the treatment of benign biliary stricture (BBS). Thus, the development of stent materials in the perspectives of structure, mechanical properties, and biocompatibility has been also studied. However, conventional metal and plastic stents have several disadvantages, such as repeated procedures to remove or exchange them, dislodgment, restenosis, biocompatibility, and poor mechanical properties. Sustainable effectiveness, attenuation and prevention of fibrosis, and biocompatibility are key factors for the clinical application of stents to BBS treatment. In addition, loading drugs could show synergistic effects with stents’ own performance. We developed a dexamethasone-eluting biodegradable stent (DBS) consisting of a sheath/core structure with outstanding mechanical properties and sustained release of dexamethasone, which maintained its functions in a BBS duct over 12 weeks in a swine model. The insertion of our DBS not only expanded BBS areas but also healed secondary ulcers as a result of the attenuation of fibrosis. After 16 weeks from the insertion, BBS areas were totally improved, and the DBS was degraded and thoroughly disappeared without re-intervention for stent removal. Our DBS would be an effective clinical tool for non-vascular diseases. Statement of significanceThis study describes the insertion of a drug-eluting biodegradable stent (DBS) into the bile duct. The sheath/core structure of DBS confers substantial durability and a sustained drug release profile. Drug released from the DBS exhibited anti-fibrotic effects without inflammatory responses in both in vitro and in vivo experiments. The DBS maintained its function over 12 weeks after insertion into the common bile duct, expanding benign biliary stricture (BBS) and reducing inflammation to heal secondary ulcers in a swine BBS model. After 16 weeks from the DBS insertion, the DBS thoroughly disappeared without re-intervention for stent removal, resulting in totally improved BBS areas. Our findings not only spotlight the understanding of the sheath/core structure of the biodegradable stent, but also pave the way for the further application for non-vascular diseases.

Injectable dexamethasone-loaded peptide hydrogel for therapy of radiation-induced ototoxicity by regulating the mTOR signaling pathway

Radiation-induced ototoxicity is associated with inflammation response and excessive reactive oxygen species in the cochlea. However, the effectiveness of many drugs in clinical settings is limited due to anatomical barriers in the inner ear and pharmacokinetic instability. To address this issue, we developed an injectable hydrogel called RADA32-HRN-dexamethasone (RHD). The RHD hydrogel possesses self-anti-inflammatory properties and can self-assemble into nanofibrous structures, ensuring controlled and sustained release of dexamethasone in the local region. Flow cytometry analysis revealed that the uptake of FITC-conjugated RHD gel by hair cells increased in a time-dependent manner. Compared to free dexamethasone solutions, dexamethasone-loaded RHD gel achieved a longer and more controlled release profile of dexamethasone. Additionally, RHD gel effectively protected against the inflammatory response, reduced excessive reactive oxygen species production, and reversed the decline in mitochondrial membrane potentials induced by ionizing radiation, leading to attenuation of apoptosis and DNA damage. Moreover, RHD gel promoted the recovery of outer hair cells and partially restored auditory function in mice exposed to ionizing radiation. These findings validated the protective effects of RHD gel against radiation-induced ototoxicity in both cell cultures and animal models. Furthermore, RHD gel enhanced the activity of the mammalian target of rapamycin (mTOR) signaling pathway, which was inhibited by ionizing radiation, thereby promoting the survival of hair cells. Importantly, intratympanic injections of RHD gel exhibited excellent biosafety and do not interfere with the anti-tumor effects of radiotherapy. In summary, our study demonstrates the therapeutic potential of injectable dexamethasone-loaded RHD hydrogel for the treatment of radiation-induced hearing loss by regulating the mTOR signaling pathway.

MRI-visible mesoporous polydopamine nanoparticles with enhanced antioxidant capacity for osteoarthritis therapy

Since the progression of osteoarthritis (OA) is closely associated with synovitis and cartilage destruction, the inhibition of inflammatory responses in synovial macrophages and reactive oxygen species (ROS) induced apoptosis in chondrocytes is crucial for OA amelioration. However, most of the current anti-inflammatory and antioxidant drugs are small molecules apt to be eliminated in vivo. Herein, mesoporous polydopamine nanoparticles (DAMM NPs) doped with arginine and manganese (Mn) ions were prepared to load dexamethasone (DEX) for OA intervention. A series of in vitro studies showed that the sustained release of DEX from DAMM NPs suppressed synovial inflammation and simultaneously inhibited toll-like receptor 3 (TLR-3) production in chondrocytes, contributing to prevention of chondrocyte apoptosis through the inflammatory factor-dependent TLR-3/NF-κB signaling pathway via modulation of macrophage-chondrocyte crosstalk. In addition, DAMM NPs exerted a predominant role in removal of ROS generated in chondrocytes. Therefore, the DEX-loaded DAMM NPs significantly attenuated OA development in mice model. Importantly, the T1-T2 magnetic contrast capabilities of DAMM NPs allowed an MRI-trackable delivery, manifesting a distinct feature widely regarded to boost the potential of nanomedicines for clinical applications. Together, our developed antioxidant-enhanced DAMM NPs with MRI-visible signals may serve as a novel multifunctional nanocarriers for prevention of OA progression.

Adhesive Composite Hydrogel Patch for Sustained Transdermal Drug Delivery To Treat Atopic Dermatitis

Atopic dermatitis (AD) is a common chronic inflammatory skin disease. Continuous administration of steroids often causes undesired side effects; hence, drug delivery systems with high loading capacities and sustained release profiles are required. Herein, adhesive hydrogels for sustained transdermal delivery of dexamethasone (DEX), a potent corticosteroid, have been suggested for AD treatment. The adhesive composite hydrogels comprise a double network of polyacrylamide (PAM) and polydopamine (PDA) embedded with extra-large-pore mesoporous silica nanoparticles (XL-MSNs). The intrinsic skin adhesiveness of the dopamine-derived PAM/PDA hydrogels is further enhanced by XL-MSN incorporation that contributes to the simultaneous enhancement of cohesion and adhesion of the hydrogel. The resulting adhesive hydrogels exhibit a high water content and strong adhesion to porcine skin. A sustained release of DEX is obtained when DEX is loaded within the pores of XL-MSNs in PAM/PDA hydrogels compared to the rapid release from the direct loading of DEX in hydrogels. Application of DEX-loaded MSN@PAM/PDA hydrogels on an AD mouse model led to the significant suppression of AD symptoms, including the restoration of the thickened epidermal layer, decrease in inflammatory cell infiltration in the skin, recovery of collagen deposition, and decreased levels of immunoglobulin E. XL-MSN-embedded adhesive hydrogels could be a potential platform for topical drug delivery to treat inflammatory skin diseases.

Coaxially Fabricated Dual-Drug Loading Electrospinning Fibrous Mat with Programmed Releasing Behavior to Boost Vascularized Bone Regeneration.

In clinical treatment, the bone regeneration of critical-size defects is desiderated to be solved, and the regeneration of large bone segment defects depends on early vascularization. Therefore, overcoming insufficient vascularization in artificial bone grafts may be a promising strategy for critical-size bone regeneration. Herein, a novel dual-drug programmed releasing electrospinning fibrous mat (EFM) with a deferoxamine (DFO)-loaded shell layer and a dexamethasone (DEX)-loaded core layer is fabricated using coaxial electrospinning technology, considering the temporal sequence of vascularization and bone repair. DFO acts as an angiogenesis promoter and DEX is used as an osteogenesis inducer. The results demonstrate that the early and rapid release of DFO promotes angiogenesis in human umbilical vascular endothelial cells and the sustained release of DEX enhances the osteogenic differentiation of rat bone mesenchymal stem cells. DFO and DEX exert synergetic effects on osteogenic differentiation via the Wnt/β-catenin signaling pathway, and the dual-drug programmed releasing EFM acquired perfect vascularized bone regeneration ability in a rat calvarial defect model. Overall, the study suggests a low-cost strategy to enhance vascularized bone regeneration by adjusting the behavior of angiogenesis and osteogenesis in time dimension.

Mesoporous Silk-Bioactive Glass Nanocomposites as Drug Eluting Multifunctional Conformal Coatings for Improving Osseointegration and Bactericidal Properties of Metal Implants.

Endowing metal implants with multifunctional traits to prevent implant-associated infections and improve osseointegration has become a pivotal facet in orthopedics and dental fixation. Herein, we report the synthesis of mesoporous 70S bioactive glass-silk fibroin nanocomposites inspired by the biomimetic organo-apatites of mineralized collagen. The mesoporous, biomimetic nanocomposites enabled loading of antibiotics (gentamicin and doxycycline) and favored their release in a rapid manner while preserving their bioactivity. Ease in modification of the mesoporous nanocomposites enabled tailoring of 3-(aminopropyl)-triethoxysilane to the silanol network of bioactive glass, which improved the loading capacity of the hydrophobic drug (dexamethasone). The modification favored the slow and sustained release of dexamethasone from the modified mesoporous nanocomposites, which is desired for mediating osteogenesis and immunomodulation. Conformal coatings of these drug-loaded nanocomposites were materialized on stainless-steel implants through a facile electrophoretic deposition (EPD) technique, wherein the deposition yield can be controlled by applied parameters. Antibiotic coatings exhibited antibacterial efficacy with bioactivity retained up to 28 days, while dexamethasone-loaded coatings favored mesenchymal stem cell adhesion and osteoinduction. The immunomodulatory roles were also ascertained, wherein M2 macrophage biasness was favored in dexamethasone-loaded coatings. The versatility of these mesoporous biomimetic nanocomposites guarantee the loading of scenario-specific drugs to aid their local delivery through the conformal EPD coatings developed over metal implants toward improving implant patency.

Shape-Defined microPlates for the Sustained Intra-articular Release of Dexamethasone in the Management of Overload-Induced Osteoarthritis.

Osteoarthritis (OA) is treated with the intra-articular injection of steroids such as dexamethasone (DEX) to provide short-term pain management. However, DEX treatment suffers from rapid joint clearance. Here, 20 × 10 μm, shape-defined poly(d,l-lactide-co-glycolide)acid microPlates (μPLs) are created and intra-articularly deposited for the sustained release of DEX. Under confined conditions, DEX release is projected to persist for several months, with only ∼20% released in the first month. In a highly rigorous murine knee overload injury model (post-traumatic osteoarthritis), a single intra-articular injection of Cy5-μPLs is detected in the cartilage surface, infrapatellar fat pad/synovium, joint capsule, and posterior joint space up to 30 days. One intra-articular injection of DEX-μPL (1 mg kg–1) decreased the expression of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, and matrix metalloproteinase (MMP)-13 by approximately half compared to free DEX at 4 weeks post-treatment. DEX-μPL also reduced load-induced histological changes in the articular cartilage and synovial tissues relative to saline or free DEX. In sum, the μPLs provide sustained drug release along with the capability to precisely control particle geometry and mechanical properties, yielding long-lasting benefits in overload-induced OA. This work motivates further study and development of particles that provide combined pharmacological and mechanical benefits.

Thermo-Responsive PLGA-PEG-PLGA Hydrogels as Novel Injectable Platforms for Neuroprotective Combined Therapies in the Treatment of Retinal Degenerative Diseases.

The present study aims to develop a thermo-responsive-injectable hydrogel (HyG) based on PLGA-PEG-PLGA (PLGA = poly-(DL-lactic acid co-glycolic acid); PEG = polyethylene glycol) to deliver neuroprotective agents to the retina over time. Two PLGA-PEG PLGA copolymers with different PEG:LA:GA ratios (1:1.54:23.1 and 1:2.25:22.5) for HyG-1 and HyG-2 development respectively were synthetized and characterized by different techniques (gel permeation chromatography (GPC), nuclear magnetic resonance (NMR), dynamic light scattering (DLS), critical micelle concentration (CMC), gelation and rheological behaviour). According to the physicochemical characterization, HyG-1 was selected for further studies and loaded with anti-inflammatory drugs: dexamethasone (0.2%), and ketorolac (0.5%), alone or in combination with the antioxidants idebenone (1 µM) and D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) (0.002%). In vitro drug release and cytotoxicity studies were performed for the active substances and hydrogels (loaded and drug-free). A cellular model based on oxidative stress was optimized for anti-inflammatory and antioxidant screening of the formulations by using retinal-pigmented epithelial cell line hTERT (RPE-1). The copolymer 1, used to prepare thermo-responsive HyG-1, showed low polydispersity (PDI = 1.22) and a strong gel behaviour at 25% (w/v) in an isotonic buffer solution close to the vitreous temperature (31–34 °C). Sustained release of dexamethasone and ketorolac was achieved between 47 and 62 days, depending on the composition. HyG-1 was well tolerated (84.5 ± 3.2%) in retinal cells, with values near 100% when the anti-inflammatory and antioxidant agents were included. The combination of idebenone and dexamethasone promoted high oxidative protection in the cells exposed to H2O2, with viability values of 86.2 ± 14.7%. Ketorolac and dexamethasone-based formulations ameliorated the production of TNF-α, showing significant results (p ≤ 0.0001). The hydrogels developed in the present study entail a novel biodegradable tool to treat neurodegenerative processes of the retina overtime.

The sustained release of dexamethasone from TiO2 nanotubes reinforced by chitosan to enhance osteoblast function and anti-inflammation activity.

Controlling macrophage response to biomaterials is critical for the reduction of inflammation after implantation. Here we designed a sustained release system from TiO2 nanotubes (TNTs) to improve osteogenesis on titanium implants with anti-inflammatory properties. TNTs (around 70nm diameter) were first fabricated on titanium surfaces by anodization, directly filled with the anti-inflammatory drug, dexamethasone (DEX) and then covered by chitosan (CHI) multilayer films. Primary osteoblast and macrophage (RAW 264.7) cells were cultured on untreated and treated titanium surfaces in vitro. Osteoblasts grown on CHI-coated Dex-filled TNTs surfaces displayed higher alkaline phosphatase (ALP) and mineralization, which was consistent with qRT-PCR analysis of osteoblastic genes including collagen type I (Col I), osteocalcin (OCN), osteopontin (OPN) and runt related transcription factor 2 (Runx2). In contrast, protein levels of nitric oxide (NO) and proinflammatory cytokines (TNF-α and IL-1β) from macrophages on Dex-filled TNTs, CHI-coated TNTs and CHI-coated Dex-filled TNTs were significantly lower, especially on CHI-coated Dex-filled TNTs surfaces compared to levels on titanium and TNTs. These results indicate that CHI-coated Dex-filled TNTs enhanced osteoblast differentiation and decreased the inflammatory response of macrophages. The approach presented here provides new insight into the modification of TNTs for the development of titanium-based implants.

The synergetic effect of bioactive molecule-loaded electrospun core-shell fibres for reconstruction of critical-sized calvarial bone defect-The effect of synergetic release on bone Formation.

ObjectivesBone regeneration is a complex process modulated by multiple growth factors and hormones during long regeneration period; thus, designing biomaterials with the capacity to deliver multiple bioactive molecules and obtain sustained release has gained an increasing popularity in recent years. This study is aimed to evaluate the effect of a novel core‐shell electrospun fibre loaded with dexamethasone (DEX) and bone morphogenetic protein‐2 (BMP‐2) on bone regeneration.Materials and methodsThe core‐shell electrospun fibres were fabricated by coaxial electrospinning technology, which were composed of poly‐D, L‐lactide (PLA) shell and poly (ethylene glycol) (PEG) core embedded with BMP‐2 and DEX‐loaded micelles. Morphology, hydrophilicity, gradation, release profile of BMP‐2 and DEX, and cytological behaviour on bone marrow mesenchymal stem cells (BMSCs) were characterized. Furthermore, the effect on bone regeneration was evaluated via critical‐sized calvarial defect model.ResultsThe electrospun fibres were featured by the core‐shell fibrous architecture and a suitable degradation rate. The sustained release of DEX and BMP‐2 was up to 562 hours. The osteogenic gene expression and calcium deposition of BMSCs were significantly enhanced, indicating the osteoinduction capacity of electrospun fibres. This core‐shell fibre could accelerate repair of calvarial defects in vivo via synergistic effect.ConclusionsThis core‐shell electrospun fibre loaded with DEX and BMP‐2 can act synergistically to enhance bone regeneration, which stands as a strong potential candidate for repairing bone defects.

Versatile Preparation of Silica Nanocapsules for Biomedical Applications

AbstractCore–shell nanocapsules are receiving increasing interest for drug delivery applications. Silica nanocapsules have been the focus of intensive studies due to their biocompatibility, versatile silica chemistry, and tunable porosity. However, a versatile one‐step preparation of silica nanocapsules with well‐defined core–shell structure, tunable size, flexible interior loading, and tailored shell composition, permeability, and surface functionalization for site‐specific drug release and therapeutic tracking remains a challenge. Herein, an interfacially confined sol–gel process in miniemulsion for the one‐step versatile preparation of functional silica nanocapsules is developed. Uniform nanocapsules with diameters from 60 to 400 nm are obtained and a large variety of hydrophobic liquids are encapsulated in the core. When solvents with low boiling point are loaded, subsequent solvent evaporation converts the initially hydrophobic cavity into an aqueous environment. Stimuli‐responsive permeability of nanocapsules is programmed by introducing disulfide or tetrasulfide bonds in the shell. Selective and sustained release of dexamethasone in response to glutathione tripeptide for over 10 d is achieved. Fluorescence labeling of the silica shell and magnetic loading in the internal cavity enable therapeutic tracking of nanocapsules by fluorescence and electron microscopies. Thus, silica nanocapsules represent a promising theranostic nanoplatform for targeted drug delivery applications.

Dexamethasone pharmacokinetics characteristics via sub-tenon microfluidic system in uveitis rabbits

The aim of this study was to investigate the plasma and ocular dexamethasone (DEX) pharmacokinetics characteristics of the sub-tenon microfluidic system (SMS) delivery of dexamethasone sodium phosphate (DEXP) in experimental autoimmune uveitis (EAU) rabbits. The SMS showed sustained DEX release and large amount of drug loading capacity by a miniature pump which connected with a tube that implanted into the sub-Tenon's sac of the EAU rabbit. The DEX concentrations in the plasma and different ocular compartments (cornea, aqueous humor, retina/choroid, sclera and vitreous humor) were quantified by Shimadzu LC–MS 2010 system. The SMS increased total drug delivery of DEX in ocular tissues as compared with traditional combined medication (subconjunctival injection combined with intravenous injection) in EAU rabbit. Moreover, the minimal amount of DEX was found in the blood, indicated that only a small amount of drug could enter into the bloodstream and causing minimal systematic side effect. Overall, the study provided evidence that SMS meet the large amount of drug loading capacity, continuous release drugs and moderate drug level in the EAU ocular tissue and minimal drug level in the blood, which indicated that SMS could be a feasible option for ocular application in clinical trials and maybe can replace or even discard systemic medications for the management of acute ocular inflammation disease.

Incorporation of dexamethasone-loaded mesoporous silica nanoparticles into mineralized porous biocomposite scaffolds for improving osteogenic activity

The development of ideal organic-inorganic composite scaffold with porous structure and favorable osteoinductive properties that mimics the extracellular matrix composition of bone, is essential for the guidance of new bone formation in orthopaedic practice. Nowadays, numerous efforts have been dedicated to constructing implantable biocomposite scaffolds with appropriate structure and bioactivity for repairing bone defects. In this study, we fabricated chitosan-alginate-gelatin (CAG)-based porous biocomposite scaffolds with calcium phosphate coating on the surface and dexamethasone (DEX)-loaded mesoporous silica nanoparticles within the scaffold, which allows sustained release of DEX for bone tissue engineering application. The inorganic components of calcium phosphate crystals formed on the wall of scaffolds were obtained through electrochemical deposition method. The hybrid mineralized scaffolds demonstrate significantly high mechanical strength and reduced swelling property compared with pristine CAG scaffolds. The in vitro proliferation and osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (BMSCs) cultured on biocomposite scaffolds were significantly enhanced. Furthermore, in vivo experiments revealed that biocomposite scaffolds with minerals deposition and DEX loading showed better new bone formation ability, as compared to pure CAG scaffold and single mineralized scaffold. Therefore, the developed biocomposite scaffolds may be highly promising as local implantable scaffolds for potential applications in bone tissue engineering.

Dexamethasone-loaded hollow hydroxyapatite microsphere promotes odontogenic differentiation of human dental pulp cells in vitro

A sustained-release system was established by synthesis of dexamethasone-loaded hollow hydroxyapatite microspheres (DHHAM). The in vitro effect of DHHAM on odontogenic differentiation of human dental pulp cells (hDPCs) was evaluated. Hollow hydroxyapatite microspheres (HHAM) are successfully manufactured using simple biomimetic one-step strategy in the presence of glycine and sodium dodecyl sulfonate. Dexamethasone (DEX) was loaded to the system after the formation of HHAM. The drug encapsulation capacity of DEX in HHAM is 40.3% and its loading efficiency is 16.7%. The cumulative release of DEX in vitro is 55% up to 35 days. Results of Real-time Polymerase Chain Reaction (Real-time PCR), alkaline phosphatase (ALP) activity and Alizarin Red S staining revealed that DHHAM can obviously promote bio-mineralization of hDPCs in the absence of osteogenic medium and enhance the gene expression of ALP, Runt-related transcription factor 2 (RUNX2), osteocalcin, dentin sialophosphoprotein (DSPP) and dentin matrix protein 1 (DMP1). The data suggest that sustained release of DEX from DHHAM could efficiently enhance odontogenic differentiation of hDPCs.

Sustained Release of Dexamethasone from Sulfobutyl Ether β-cyclodextrin Modified Self-Assembling Peptide Nanoscaffolds in a Perinatal Rat Model of Hypoxia-Ischemia.

Inflammation plays a critical role in the development of hypoxia-ischemia (HI) induced newborn brain damage. A localized, sustained delivery of dexamethasone (Dex) through an intracerebral injection could reduce the inflammatory response in the injured perinatal brain while avoiding unnecessary side effects. Herein, investigated using anionic sulfobutyl ether β-cyclodextrin (SBE-β-CD) to load Dex in the (RADA)4 nanofiber networks as a means of reducing the inflammatory response to HI injury is investigated. The ionic interaction between SBE-β-CD and (RADA)4 dramatically affects nanofiber formation and the stability of the nanoscaffold is highly dependent on the SBE-β-CD/(RADA)4 ratio. It is observed that the Dex release rate is affected by the concentration of SBE-β-CD and (RADA)4 peptide. A higher concentration of SBE-β-CD or (RADA)4 results in a higher drug encapsulation efficiency and slower release rate of Dex. This phenomenon may be related to the structure of fiber bundles. Animal studies show that nanoscaffold loaded with Dex inhibits both microglia activation and glial scar formation compared to controls (Dex alone or nanoscaffold alone) within 2 days of injury. It is thought that this is a step toward building a multifaceted nanoscaffold that can be used to treat HI events in perinates.

Subcritical carbon dioxide foaming of polycaprolactone for bone tissue regeneration

The preparation of three-dimensional polycaprolactone scaffolds using dense CO2 as foaming agent, without supercritical conditions, was evaluated in this study towards future applications in bone repair. Herein, 3D foams were obtained at 5.0 MPa and 45 °C. To induce bioactivity, β-tricalcium phosphate (β-TCP, 10 wt%) and dexamethasone (5 and 10 wt%) were dispersed in the scaffolds. Foams revealed a pore size range of 164–882 μm, 73–99% porosity and 79–99% interconnectivity, assessed by micro-computed tomography, and a Young modulus of 1.76–2.92 MPa. Dexamethasone did not impair morphology of the matrices in comparison with PCL+β-TCP, which presented a water uptake of nearly 100% after 14 days. A sustained release of dexamethasone was achieved over 35 days in physiologic solution. This study reports the feasibility of using dense CO2 to produce in one-step a porous matrix loaded with active agents opening new possibilities towards injectable systems for in situ foaming.

Sustained release of dexamethasone from drug‐loading PLGA scaffolds with specific pore structure fabricated by supercritical CO2 foaming

ABSTRACTInducing differentiation of bone marrow stem cells to generate new bone tissue is highly desirable by controlling the release of some osteoinductive or osteoconductive factors from porous scaffolds. In this study, dexamethasone was selected as a representative of small molecule drugs and dexamethasone‐loading porous poly(lactide‐co‐glycolide) (PLGA) scaffolds were successfully fabricated by supercritical CO2 foaming. Scanning electron microscopy images showed that scaffolds had rough and relatively interconnected pores facilitating cells adhesion and growth. Specially, dexamethasone which was incorporated into PLGA matrix in a molecularly dispersed state could serve as a nucleation agent to be helpful for the formation of interconnected pores. Dexamethasone‐loading porous PLGA scaffolds exhibited sustained release profile, and the delivery of dexamethasone from porous scaffolds could last for up to 2 months. The cumulative released amount of dexamethasone was relevant with drug loading capacity (1.66%–2.95%) and pore structure of scaffolds; while the release behavior was anomalous (non‐Fickian) transport by fitting with the simple exponential equation, which had a diffusional exponent n higher than 0.5. It is feasible to fabricate drug‐loading porous scaffolds by supercritical CO2 foaming with specific pore structure and sustained release profile, which can be well applied in bone tissue engineering. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46207.

Preparation of dexamethasone-loaded biphasic calcium phosphate nanoparticles/collagen porous composite scaffolds for bone tissue engineering.

Scaffolds play a crucial role for regeneration of large bone defects. Biomimetic scaffolds having the same composition of natural bone and a controlled release of osteoinductive factors are desirable for promotion of bone regeneration. In this study, composite scaffolds of collagen and biphasic CaP nanoparticles (BCP NPs) with a controlled release nature of dexamethasone (DEX) were prepared and their porous structures were controlled by using ice particulates. In vitro cell culture and in vivo implantation experiments demonstrated the composite scaffolds exerted synergistic effects on the osteogenic differentiation of hMSCs and bone regeneration. The composite scaffolds also showed promotive effect on the formation of capillary blood vessels in the regenerated bone. This study is the first research to prepare DEX-loaded BCP NPs/collagen porous composite scaffolds. The superior performance of the composite scaffolds indicates the composite scaffolds should be useful for bone tissue engineering.