Functionally graded hydrogels with opposing biochemical cues for osteochondral tissue engineering.

Osteochondral tissue (OC) repair remains a significant challenge in the field of musculoskeletal tissue engineering. OC tissue displays a gradient structure characterized by variations in both cell types and extracellular matrix components, from cartilage to the subchondral bone. These functional gradients observed in the native tissue have been replicated to engineer OC tissue.

Polyhydroxybutyrate-based osteoinductive mineralized electrospun structures that mimic components and tissue interfaces of the osteon for bone tissue engineering.

Scaffolds for bone tissue engineering should enable regeneration of bone tissues with its native hierarchically organized extracellular matrix (ECM) and multiple tissue interfaces. To achieve this, inspired by the structure and properties of bone osteon, we fabricated polyhydroxybutyrate (PHB)-based mineralized electrospun fibrous scaffolds. After studying multiple PHB-based fibers, we chose 7%PHB/1%Gelatin fibers (PG) to fabricate mineralized fibers that mimic mineralized collagen fibers in bone.

Engineering sulfated polysaccharides and silk fibroin based injectable IPN hydrogels with stiffening and growth factor presentation abilities for cartilage tissue engineering.

The extracellular matrix (ECM) presents a framework for various biological cues and regulates homeostasis during both developing and mature stages of tissues. During development of cartilage, the ECM plays a critical role in endowing both biophysical and biochemical cues to the progenitor cells. Hence, designing microenvironments that recapitulate these biological cues as provided by the ECM during development may facilitate the engineering of cartilage tissue.

Directing ligament-mimetic bi-directional cell organization in scaffolds through zone-specific microarchitecture for ligament tissue engineering.

Ligament tissues exhibit zone-specific anisotropic cell organization. The cells in ligament-proper are longitudinally oriented, whereas, the cells in epiligament are circumferentially oriented. Therefore, scaffolds developed to regenerate ligament tissues should possess adequate architectural features to govern ligament-mimetic bi-directional cell organization.

Piperlongumine mediates amelioration of osteoarthritis via inhibition of chondrocyte senescence and inflammation in a goat ex vivo model.

In osteoarthritis (OA), chondrocytes manifest senescence, which results in a vicious signaling loop that aids the progression of the disease. More specifically, inflammation-associated senescence is one of the major regulators of the initiation and progression of OA. Therefore, we targeted senescence through inflammation with a pharmacological approach for OA amelioration.

Targeting multiple disease hallmarks using a synergistic disease-modifying drug combination ameliorates osteoarthritis via inhibition of senescence and inflammation.

Aims: Osteoarthritis (OA), is a debilitating disease characterized by progressive cartilage degradation, synovial inflammation, and chondrocyte senescence. Various treatment agents independently targeting these hallmarks have been investigated. However, due to the complex multifaceted nature of OA, no disease-modifying osteoarthritis drugs are clinically available.

Converse modulation of Wnt/β-catenin signaling during expansion and differentiation phases of Infrapatellar fat pad-derived MSCs for improved engineering of hyaline cartilage.

Mesenchymal stem cells (MSCs) are potential candidates in cell-based therapy for cartilage repair and regeneration. However, during chondrogenic differentiation, MSCs undergo undesirable hypertrophic maturation. This poses a risk of ossification in the neo-tissue formed that eventually impedes the clinical use of MSCs for cartilage repair.

Sulfated carboxymethylcellulose mediated enhancement of Timp3 efficacy synergistically attenuates osteoarthritis through inhibition of NFκB and JNK.

Osteoarthritis (OA) is a prevalent degenerative joint condition with no effective disease modifying treatments. In this study, we aimed to address multiple OA hallmarks using a combination of pro-chondrogenic sulfated carboxymethylcellulose (sCMC) and anti-catabolic tissue inhibitor of metalloproteases 3 (Timp3) in relevant disease systems. Firstly, we chemically sulfated carboxymethylcellulose to impart a negative charge and improve the stability of cationic Timp3.

Facile synthesis of multi-faceted, biomimetic and cross-protective nanoparticle-based vaccines for drug-resistant Shigella: a flexible platform technology.

Background: No commercial vaccines are available against drug-resistant Shigella due to serotype-specific/narrow-range of protection. Nanoparticle-based biomimetic vaccines involving stable, conserved, immunogenic proteins fabricated using facile chemistries can help formulate a translatable cross-protective Shigella vaccine. Such systems can also negate cold-chain transportation/storage thus overcoming challenges prevalent in various settings.

Stable Recombinant Invasion Plasmid Antigen C (IpaC)-Based Single Dose Nanovaccine for Shigellosis.

Shigellosis, caused by the bacteria , is the leading cause of bacterial diarrhea and the second leading cause of diarrheal death among children under the age of five. Unfortunately, strains have acquired resistance to antibiotics, and a commercial vaccine is yet to be available. We have previously demonstrated that serotype 1 (Sd1)-based recombinant, stabilized, "invasion plasmid antigen C" (IpaC; 42 kDa) protein can induce robust immune responses in BALB/c mice against a challenge of a high dose of heterologous when immunized via three intranasal doses of IpaC without an adjuvant.

Isolation, Expansion, and Differentiation of Mesenchymal Stem Cells from the Infrapatellar Fat Pad of the Goat Stifle Joint.

The IFP, present in the knee joint, serves as a promising source of MSCs. The IFP is an easily accessible tissue as it is routinely resected and discarded during arthroscopic procedures and knee replacement surgeries. Additionally, its removal is associated with minimal donor site morbidity.

Sulfated carboxymethylcellulose-based scaffold mediated delivery of Timp3 alleviates osteoarthritis.

Osteoarthritis (OA) is a debilitating progressive joint disease with high incidence and socioeconomic burden. However, no disease-modifying treatment is currently available for OA. Here, we report a sulfated carboxymethylcellulose-based scaffold mediated delivery of tissue inhibitor of metalloprotease 3 (Timp3) as a disease-modifying therapeutic strategy for OA.

A human osteoarthritis mimicking goat cartilage explant-based disease model for drug screening.

Although osteoarthritis (OA) is the most prevalent human joint disease with a large socioeconomic burden, it remains a neglected disease with no clinically approved disease modifying therapies. One of the key reasons for this is that the available disease models poorly recapitulate human OA-like traits, possibly because of the challenge of mimicking the disease in an ECM-rich cartilage tissue. In this study, we report the establishment and validation of a clinically relevant ex vivo OA model using IL1β-treated goat articular cartilage explants.

Bioinspired Injectable Hydrogels Dynamically Stiffen and Contract to Promote Mechanosensing-Mediated Chondrogenic Commitment of Stem Cells.

Developing stiff and resilient injectable hydrogels that can mechanically support load-bearing joints while enabling chondrogenic differentiation of stem cells is a major challenge in the field of cartilage tissue engineering. In the present work, a triple-network injectable hydrogel system was engineered using silk fibroin, carboxymethyl cellulose (CMC), and gelatin. The developed hydrogel demonstrated a simultaneous increase in both stiffness and contraction over time, thereby imparting a four-dimensional (4D) evolving niche to the cells.

Mesoporous Silica Nanoparticle-Based Combination of Niclosamide and Doxorubicin: Effect of Treatment Regimens on Breast Cancer Subtypes.

Overexpressed Wnt/β-catenin signaling acts as a major cancer driver and plays an important role in the development of resistance against cancer chemotherapy. Therefore, the combinatorial approach of downregulating Wnt/β-catenin signaling along with using a chemotherapeutic agent may improve cancer therapy. However, systemic administration of free anticancer agents is nonspecific and poses serious side effects.

Carboxylated chitosan-mediated improved efficacy of mesoporous silica nanoparticle-based targeted drug delivery system for breast cancer therapy.

Nanoparticle-based targeting of overexpressed cell-surface receptors is a promising strategy that provides precise delivery of drugs to cancer cells. In the present study, we developed highly reproducible and monodispersed, chitosan-coated (pH-responsive), doxorubicin-loaded, aptamer-mesoporous silica nanoparticle (MSN) bioconjugates for actively targeting breast cancer cells harboring overexpression of EGF receptors (EGFR/HER2). The developed targeted MSNs demonstrated higher uptake and cytotoxicity of triple negative and HER2 positive breast cancer cells when compared to non-targeted MSNs.

Development of a Self-Adjuvanting, Cross-Protective, Stable Intranasal Recombinant Vaccine for Shigellosis.

With the acquirement of antibiotic resistance, has resulted in multiple epidemics of shigellosis, an infectious diarrheal disease, causing thousands of deaths per year. Unfortunately, there are no licensed vaccines, primarily due to low or serotype-specific immunogenicity. Thus, conserved subunit vaccines utilizing recombinant invasion plasmid antigens (Ipa) have been explored as cross-protective vaccine candidates.

Simultaneous amelioration of diabetic ocular complications in lens and retinal tissues using a non-invasive drug delivery system.

Topically administered delivery systems for ophthalmic applications have been studied for the treatment of anterior or posterior eye diseases. However, simultaneous treatment of both anterior and posterior eye diseases has not been explored. In this study, we fabricated a topically administrable polymeric nanoparticle (NP)- based delivery system consisting of pluronic®F-68 shell and polycaprolactone core for the simultaneous treatment of both anterior and posterior eye diseases.

A non-invasive nanoparticle-based sustained dual-drug delivery system as an eyedrop for endophthalmitis.

Endophthalmitis is an infectious disease that affects the entire eye spreading to the internal retinal layers and the vitreous and causes severe sight-threatening conditions. Current treatment strategies rely on intraocular injections of antibiotics that are invasive, may lead to procedural complications and, ultimately, blindness. In this study, we developed a non-invasive strategy as an eyedrop containing nanoparticle-based dual-drug delivery system in which the hydrophobic poly-L-lactide core was loaded with azithromycin or triamcinolone acetonide, and the hydrophilic shell was made of chitosan.

A Synergistic Combination of Niclosamide and Doxorubicin as an Efficacious Therapy for All Clinical Subtypes of Breast Cancer.

Drug resistance is one of the major hurdles in the success of cancer chemotherapy. Notably, aberrantly expressed Wnt/β-catenin signaling plays a major role in the initiation and maintenance of oncogenesis along with development of chemoresistance. Therefore, the combinatorial approach of targeting Wnt/β-catenin pathway along with using a chemotherapeutic agent seems to be a promising strategy to improve cancer therapy.

Sulfated carboxymethylcellulose conjugated electrospun fibers as a growth factor presenting system for tissue engineering.

Inspired by the natural electrostatic interaction of cationic growth factors with anionic sulfated glycosaminoglycans in the extracellular matrix, we developed electrospun poly(hydroxybutyrate)/gelatin (PG) fibers conjugated with anionic sulfated carboxymethylcellulose (sCMC) to enable growth factor immobilization via electrostatic interaction for tissue engineering. The fibrous scaffold bound cationic molecules, was cytocompatible and exhibited a remarkable morphological and functional stability. Transforming growth factor-β1 immobilized on the sCMC conjugated fibers was retained for at least 4 weeks with negligible release (3%).

Role of Physicochemical Properties of Protein in Modulating the Nanoparticle-Bio Interface.

Nanoparticles, on exposure to the biological milieu, tend to interact with macromolecules to form a biomolecular corona. The biomolecular corona confers a unique biological identity to nanoparticles, and its protein composition plays a deterministic role in the biological fate of nanoparticles. The physiological behavior of proteins stems from their physicochemical properties, including surface charge, hydrophobicity, and structural stability.

In vivo cartilage regeneration in a multi-layered articular cartilage architecture mimicking scaffold.

Aims: Extracellular matrix (ECM) and its architecture have a vital role in articular cartilage (AC) structure and function. We hypothesized that a multi-layered chitosan-gelatin (CG) scaffold that resembles ECM, as well as native collagen architecture of AC, will achieve superior chondrogenesis and AC regeneration. We also compared its in vitro and in vivo outcomes with randomly aligned CG scaffold.

Polycaprolactone as biomaterial for bone scaffolds: Review of literature.

Bone tissue engineering using polymer based scaffolds have been studied a lot in last decades. Considering the qualities of all the polymers desired to be used as scaffolds, Polycaprolactone (PCL) polyester apart from being biocompatible and biodegradable qualifies to an appreciable level due its easy availability, cost efficacy and suitability for modification. Its adjustable physio-chemical state, biological properties and mechanical strength renders it to withstand physical, chemical and mechanical, insults without significant loss of its properties.

Spatio-temporal control on the delivery of triamcinolone acetonide using polymeric nanoparticles reduces steroid induced cataract.

Development of topically administered drug delivery systems for the treatment of ocular diseases have majorly focused on enhancing bioavailability of drugs in the ocular tissues. However, control of spatial distribution of topically administered drugs so as to restrict/avoid drug bioavailability at sensitive ocular tissues that are prone to drug induced adverse effects has not been explored. In this study, we aimed to reduce the bioavailability of topically administered corticosteroid, triamcinolone acetonide (TA) in lens via controlled spatial distribution in order to minimize TA induced posterior subcapsular cataract (PSC).