Injectable pH and Thermo-Responsive Hydrogel Scaffold with Enhanced Osteogenic Differentiation of Preosteoblasts for Bone Regeneration.

Bone fractures are common in the geriatric population and pose a great economic burden worldwide. While traditional methods for repairing bone defects have primarily been autografts, there are several drawbacks limiting its use. Bone graft substitutes have been used as alternative strategies to improve bone healing.

Ultra-long-acting in-situ forming implants with cabotegravir protect female macaques against rectal SHIV infection.

Ultra-long-acting delivery platforms for HIV pre-exposure prophylaxis (PrEP) may increase adherence and maximize public health benefit. We report on an injectable, biodegradable, and removable in-situ forming implant (ISFI) that is administered subcutaneously and can release the integrase inhibitor cabotegravir (CAB) above protective benchmarks for more than 6 months. CAB ISFIs are well-tolerated in female mice and female macaques showing no signs of toxicity or chronic inflammation.

Cellular responses to nanoscale substrate topography of TiO nanotube arrays: cell morphology and adhesion.

Nanotopographical features can be beneficial in augmenting cell functions and increasing osteogenic potential. However, the relationships between surface topographies and biological responses are difficult to establish due to the difficulty in controlling the surface topographical features at a low-nanometre scale. Herein, we report the fabrication of well-defined controllable titanium dioxide (TiO) nanotube arrays with a wide range of pore sizes, 30-175 nm in diameter, and use of the electrochemical anodization method to assess the effect of surface nanotopographies on cell morphology and adhesion.

Injectable pH Thermo-Responsive Hydrogel Scaffold for Tumoricidal Neural Stem Cell Therapy for Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults and despite recent advances in treatment modalities, GBM remains incurable. Injectable hydrogel scaffolds are a versatile delivery system that can improve delivery of drug and cell therapeutics for GBM. In this report, we investigated an injectable nanocellulose/chitosan-based hydrogel scaffold for neural stem cell encapsulation and delivery.

Graphene-incorporated hyaluronic acid-based hydrogel as a controlled Senexin A delivery system.

Perivascular delivery of therapeutic agents against established aetiologies for occlusive vascular remodelling has great therapeutic potential for vein graft failure. However, none of the perivascular drug delivery systems tested experimentally have been translated into clinical practice. In this study, we established a novel strategy to locally and sustainably deliver the cyclin-dependent kinase 8/19 inhibitor Senexin A (SenA), an emerging drug candidate to treat occlusive vascular disease, using graphene oxide-hybridised hyaluronic acid-based hydrogels.

Effects of Drug Physicochemical Properties on In-Situ Forming Implant Polymer Degradation and Drug Release Kinetics.

In-situ forming implants (ISFIs) represent a simple, tunable, and biodegradable polymer-based platform for long-acting drug delivery. However, drugs with different physicochemical properties and physical states in the polymer-solvent system exhibit different drug release kinetics. Although a few limited studies have been performed attempting to elucidate these effects, a large, systematic study has not been performed until now.

Cell-Laden Nanocellulose/Chitosan-Based Bioinks for 3D Bioprinting and Enhanced Osteogenic Cell Differentiation.

3D bioprinting has recently emerged as a very useful tool in tissue engineering and regenerative medicine. However, developing suitable bioinks to fabricate specific tissue constructs remains a challenging task. Herein, we report on a nanocellulose/chitosan-based bioink, which is compatible with a 3D extrusion-based bioprinting technology, to design and engineer constructs for bone tissue engineering and regeneration applications.

A mucoadhesive biodissolvable thin film for localized and rapid delivery of lidocaine for the treatment of vestibulodynia.

Vestibulodynia (VBD), an idiopathic pain disorder characterized by erythema and pain of the vulvar vestibule (the inner aspect of the labia minora and vaginal opening), is the most common cause of sexual pain for women of reproductive age. Women also feel discomfort with contact with clothing and tampon use. As most women with this disorder only have pain with provocation of the tissue, topical anesthetics applied to the vestibule are the current first line treatment for temporary pain relief.

Biodegradable polymeric solid implants for ultra-long-acting delivery of single or multiple antiretroviral drugs.

Lack of adherence is a key barrier to a successful human immunodeficiency virus (HIV) treatment and prevention. We report on an ultra-long-acting (ULA) biodegradable polymeric solid implant (PSI) that can accommodate one or more antiretrovirals (e.g.

Steroid Eluting Esophageal-Targeted Drug Delivery Devices for Treatment of Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is a chronic atopic disease that has become increasingly prevalent over the past 20 years. A first-line pharmacologic option is topical/swallowed corticosteroids, but these are adapted from asthma preparations such as fluticasone from an inhaler and yield suboptimal response rates. There are no FDA-approved medications for the treatment of EoE, and esophageal-specific drug formulations are lacking.

A new engineering process of biodegradable polymeric solid implants for ultra-long-acting drug delivery.

We present a long-acting (LA) biodegradable polymeric solid implant (PSI) fabricated using a new process combining in-situ phase inversion and compression. This robust process allows fabrication of solid implants that can have different shapes and sizes, accommodate high drug payloads, and provide sustained drug release over several months. Herein the integrase inhibitor dolutegravir (DTG) was used to develop PSIs for HIV prevention.

Hyaluronic acid-based hydrogels with tobacco mosaic virus containing cell adhesive peptide induce bone repair in normal and osteoporotic rats.

Tobacco mosaic virus (TMV) has been studied as a multi-functional agent for bone tissue engineering. An osteo-inductive effect of wild-type TMV has been reported, as it can significantly enhance the bone differentiation potential of bone marrow stromal cells both on a two-dimensional substrate and in a three-dimensional (3D) hydrogel system. A TMV mutant (TMV-RGD1) was created which featured the adhesion peptide arginyl-glycyl-aspartic acid (RGD), the most common peptide motif responsible for cell adhesion to the extracellular matrix, on the surface of the virus particle to enhance the bio-functionality of the scaffold material.

Nanotopographical Cues Mediate Osteogenesis of Stem Cells on Virus Substrates through BMP-2 Intermediate.

Recent studies have demonstrated rapid osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) on substrates with plant virus modified nanotopographical cues as a promising strategy for bone repair; however, the mechanisms remain unclear. We hypothesized that the highly structurally ordered virus coat proteins, responsible for targeting specific cellular components, are critical for the osteogenesis promotion. In this study, hybrid viral gold nanorods were prepared to explore the effects of highly ordered arranged virus coat proteins on osteogenic differentiation of BMSCs.

Enhanced Bone Defect Repair by Polymeric Substitute Fillers of MultiArm Polyethylene Glycol-Crosslinked Hyaluronic Acid Hydrogels.

Bone regeneration is still one of the greatest challenges for the treatment of bone defects since no current clinical approach has been proven effective. To develop an alternative biodegradable bone graft material, multiarm polyethylene glycol (PEG) crosslinked hyaluronic acid (HA) hydrogels are synthesized and applied to promote osteogenesis of mesenchymal stem cells (MSCs) with the ultimate goal for bone defect repair. The multiarm PEG-HA hydrogels provide a significant improvement of alkaline phosphatase (ALP) activity and calcium mineralization of the in vitro encapsulated MSCs under osteogenic condition after 3, 7, and 28 days.

Polyamidoamine dendrimer-PEG hydrogel and its mechanical property on differentiation of mesenchymal stem cells.

Background: Biocompatible hydrogel systems with tunable mechanical properties have been reported to influence the behavior and differentiation of mesenchymal stem cells (MSCs).

Objective: To develop a functionalized hydrogel system with well-defined chemical structures and tunable mechanical property for regulation of stem cell differentiation.

Methods: An in situ-forming hydrogel system is developed by crosslinking vinyl sulfone functionalized polyamidoamine (PAMAM) dendrimer and multi-armed thiolated polyethylene glycol (PEG) through a thiol-ene Michael addition in aqueous conditions.

Optical conductivity-based ultrasensitive mid-infrared biosensing on a hybrid metasurface.

Optical devices are highly attractive for biosensing as they can not only enable quantitative measurements of analytes but also provide information on molecular structures. Unfortunately, typical refractive index-based optical sensors do not have sufficient sensitivity to probe the binding of low-molecular-weight analytes. Non-optical devices such as field-effect transistors can be more sensitive but do not offer some of the significant features of optical devices, particularly molecular fingerprinting.

A dielectric affinity glucose microsensor using hydrogel-functionalized coplanar electrodes.

This paper presents a dielectric affinity microsensor that consists of an in situ prepared hydrogel attached to a pair of coplanar electrodes for dielectrically based affinity detection of glucose in subcutaneous tissue in continuous glucose monitoring applications. The hydrogel, incorporating -3-acrylamidophenylboronic acid that recognizes glucose via affinity binding, is synthetically prepared on the electrodes via in situ gelation. When implanted in subcutaneous tissue, glucose molecules in interstitial fluid diffuse rapidly through the hydrogel and bind to the phenylboronic acid moieties.

Influence of Cross-Linkers on the in Vitro Chondrogenesis of Mesenchymal Stem Cells in Hyaluronic Acid Hydrogels.

This study aims to investigate the effect of the structures of cross-linkers on the in vitro chondrogenic differentiation of bone mesenchymal stem cells (BMSCs) in hyaluronic acid (HA)-based hydrogels. The hydrogels were prepared by the covalent cross-linking of methacrylated HA with different types of thiol-tailored molecules, including dithiothreitol (DTT), 4-arm poly(ethylene glycol) (PEG), and multiarm polyamidoamine (PAMAM) dendrimer using thiol-ene "click" chemistry. The microstructure, mechanical properties, diffusivity, and degradation rates of the resultant hydrogels were controlled by the structural feature of different cross-linkers.

A hydrogel-based glucose affinity microsensor.

We present a hydrogel-based affinity microsensor for continuous glucose measurements. The microsensor is based on microelectromechanical systems (MEMS) technology, and incorporates a synthetic hydrogel that is attached to the device surface via polymerization. Glucose molecules that diffuses into and out of the device binds reversibly with boronic acid groups in the hydrogel via affinity binding, and causes changes in the dielectric properties of the hydrogel, which can be measured using a MEMS capacitive transducer to determine the glucose concentration.

Promotion of In Vitro Chondrogenesis of Mesenchymal Stem Cells Using In Situ Hyaluronic Hydrogel Functionalized with Rod-Like Viral Nanoparticles.

This study focuses on the development of injectable hydrogels to mimic the cartilage microenvironment using hyaluronic acid (HA) derivatives as starting materials. Cysteine-inserted Tobacco mosaic virus (TMV) mutants (TMV1cys) could be cross-linked to methacrylated hyaluronic acid (MeHA) polymers by thiol-ene "click" chemistry and form hydrogels under physiological condition. The resulting hydrogels could promote in vitro chondrogenesis of bone marrow mesenchymal stem cells (BMSCs) significantly higher than that in the TMV-free HA hydrogels by upregulating bone morphogenetic protein-2 (BMP-2) expression and enhancing collagen accumulation.

Thiol-ene crosslinking polyamidoamine dendrimer-hyaluronic acid hydrogel system for biomedical applications.

A series of alkene functionalized polyamidoamine (PAMAM) dendrimers were synthesized to prepare in situ forming hydrogels with varied gelation time and mechanical properties through crosslinking with thiolated hyaluronic acid (HS-HA). By varying the alkenyl groups on the dendrimers, the gelation time displayed a large range from 8 seconds to 18 hours, and the modulus of the hydrogels ranged from 36 to 183 Pa under experimental conditions. Investigation by (1)H-NMR spectroscopy revealed that the gelation time and the stiffness of the hydrogels were governed by the degree of electron deficiency of alkenyl groups on the dendrimers.

Synthesis of PAMAM dendrimer-based fast cross-linking hydrogel for biofabrication.

Hydrogels possess great potential in biofabrication because they allow cell encapsulation and proliferation in a highly hydrated three-dimensional environment, and they provide biologically relevant chemical and physical signals. However, development of hydrogel systems that mimic the complexity of natural extracellular matrix remains a challenge. In this study, we report the development of a binary hydrogel system containing a synthetic poly(amido amine) (PAMAM) dendrimer and a natural polymer, i.