Chitin Scaffolds in Tissue Engineering

Tissue engineering/regeneration is based on the hypothesis that healthy stem/progenitor cells either recruited or delivered to an injured site, can eventually regenerate lost or damaged tissue. Most of the researchers working in tissue engineering and regenerative technology attempt to create tissue replacements by culturing cells onto synthetic porous three-dimensional polymeric scaffolds, which is currently regarded as an ideal approach to enhance functional tissue regeneration by creating and maintaining channels that facilitate progenitor cell migration, proliferation and differentiation. The requirements that must be satisfied by such scaffolds include providing a space with the proper size, shape and porosity for tissue development and permitting cells from the surrounding tissue to migrate into the matrix. Recently, chitin scaffolds have been widely used in tissue engineering due to their non-toxic, biodegradable and biocompatible nature. The advantage of chitin as a tissue engineering biomaterial lies in that it can be easily processed into gel and scaffold forms for a variety of biomedical applications. Moreover, chitin has been shown to enhance some biological activities such as immunological, antibacterial, drug delivery and have been shown to promote better healing at a faster rate and exhibit greater compatibility with humans. This review provides an overview of the current status of tissue engineering/regenerative medicine research using chitin scaffolds for bone, cartilage and wound healing applications. We also outline the key challenges in this field and the most likely directions for future development and we hope that this review will be helpful to the researchers working in the field of tissue engineering and regenerative medicine

Nano polydopamine crosslinked thiol-functionalized hyaluronic acid hydrogel for angiogenic drug delivery

Crosslinking of polymeric network using nanoparticles by physical or chemical method to obtain hydrogel is an emerging approach. Herein, we synthesized Polydopamine (PDA) nanoparticles via oxidative self-polymerization of dopamine in water-ethanol mixture. Thiol-functionalized hyaluronic acid was developed using cysteamine and hyaluronic acid (HA-Cys) via 1-Ethyl-3-(3-Dimethylaminopropyl) Carbodiimide - N-hydroxysuccinimide (EDC-NHS) crosslinking chemistry. Developed HA-Cys conjugate was cross-linked using PDA nanoparticles via Michael-type addition reaction. Synthesized nanoparticles were monodisperse with size of 124 +/- 8 nm and had spherical morphology. FTIR characterization confirmed successful synthesis of HA-Cys conjugate and subsequent crosslinking with PDA nanoparticles. Rheological characterization revealed that hydrogels were injectable in nature with good mechanical stability. Dimethyloxalylglycine (DMOG) loaded PDA nanoparticle showed sustained drug release for period of 7 days from composite hydrogel. Hydrogel microenvironment facilitated enhanced endothelial cell migration, proliferation and attachment. Furthermore, in response to release of DMOG from developed hydrogel, cells showed enhanced capillary tube formation in vitro. Overall, these results demonstrate that PDA cross-linked thiol-functionalized hydrogel was developed in a facile manner under physiological conditions. These developed hydrogels could be potentially used in tissue engineering and drug delivery

Role of FGF-18 in Bone Regeneration

In tissue engineering, three key components are cells, biological/mechanical cues, and scaffolds. Biological cues are normally proteins such as growth factors and their derivatives, bioactive molecules, and the regulators of a gene. Numerous growth factors such as VEGF, FGF, and TGF-β are being studied and applied in different studies. The carriers used to release these growth factors also play an important role in their functioning. From the early part of the 1990s, more research has beenconductedon the role of fibroblast growth factors on the various physiological functions in our body. The fibroblast growth factor family contains 22 members. Fibroblast growth factors such as 2, 9, and 18 are mainly associated with the differentiation of osteoblasts and in bone regeneration. FGF-18 stimulates the PI3K/ERK pathway and smad1/5/8 pathway mediated via BMP-2 by blocking its antagonist, which is essential for bone formation. FGF-18 incorporated hydrogel and scaffolds had showed enhanced bone regeneration. This review highlights these functions and current trends using this growth factor and potential outcomes in the field of bone regeneration

Injectable Amorphous Chitin-Agarose Composite Hydrogels for Biomedical Applications

Injectable hydrogels are gaining popularity as tissue engineering constructs because of their ease of handling and minimal invasive delivery. Making hydrogels from natural polymers helps to overcome biocompatibility issues. Here, we have developed an Amorphous Chitin (ACh)-Agarose (Agr) composite hydrogel using a simpletechnique. Rheological studies, such as viscoelastic behavior (elastic modulus, viscous modulus, yield stress, and consistency), inversion test, and injectability test, were carried out for different ACh-Agr concentrations. The composite gel, having a concentration of 1.5% ACh and 0.25% Agr, showed good elastic modulus (17.3 kPa), yield stress (3.8 kPa), no flow under gravity, injectability, and temperature stability within the physiological range. Based on these studies, the optimum concentration for injectability was found to be 1.5% ACh and 0.25% Agr. This optimized concentration was used for further studies and characterized using FT-IR and SEM. FT-IR studies confirmed the presence of ACh and Agr in the composite gel. SEM results showed that the lyophilized composite gel had good porosity and mesh like networks. The cytocompatibility of the composite gel was studied using human mesenchymal stem cells (hMSCs). The composite gels showed good cell viability.These results indicated that this injectable composite gel can be used for biomedical applications

A Multi-Stimuli Responsive Alginate Nanogel for Anticancer Chemo-Photodynamic Therapy

Stimuli-responsive nanosystems enable highly effective targeting and therapeutic functions, including chemotherapy and photodynamic therapy (PDT). Traditional PDT alone cannot effectively eradicate the tumor burden; combined with chemotherapy, this combination presents a powerful treatment modality to modulate the tumor microenvironment (TME). Herein, we report a multi-stimulus responsive alginate nanogel that responds to the change in pH and redox potential in the TME. We coupled oxidized alginate with 4-mercapto phenylboronic acid and pheophorbide-a (a hydrophobic photosensitizer) and conjugated with adipic acid dihydrazide to design the nanogels. Further, we encapsulated doxorubicin, a cytotoxic agent, in the nanogel to enable chemotherapy. The alginate nanogel exhibited the pH-sensitive release of both pheophorbide-a and doxorubicin and simultaneously reduced the redox potential that enhanced PDT by increasing reactive oxygen species production. Our results demonstrate that the multi-stimuli responsive alginate nanogel enhances toxicity in breast cancer and melanoma.This is a manuscript of an article published as Pillarisetti, Shameer, Veena Vijayan, Jayakumar Rangasamy, Rizia Bardhan, Saji Uthaman, and In-Kyu Park. "A Multi-Stimuli Responsive Alginate Nanogel for Anticancer Chemo-Photodynamic Therapy." Journal of Industrial and Engineering Chemistry (2023). DOI: 10.1016/j.jiec.2023.03.053. Copyright 2023 The Korean Society of Industrial and Engineering Chemistry. Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0). Posted with permission

Chitosan-based nanoparticles in cancer therapy

In recent years, many nanotechnology platforms in the area of medical biology, including cancer therapy, have attracted remarkable attention. In particular, research in targeted, polymeric nanoparticles for cancer therapy has increased dramatically in the past 5-10 years. However, the potential success of nanoparticles in the clinic relies on consideration of important parameters such as nanoparticle fabrication strategies, their physical properties, drug loading efficiencies, drug release potential, and, most importantly, minimum toxicity of the carrier itself. Recent work has suggested that chitosan materials hold much promise in advancing nanoparticle-based therapeutics. The field of oncology could soon be revolutionized by novel strategies for therapy employing chitosan-based nanotherapeutics. Several aspects of cancer therapy would be involved. Chitosans can also be applied to a variety of cancer therapies to improve their safety and efficacy. Further applications of chitosans in cancer therapy are being examined. This review focuses on providing brief updates on chitosan nanoparticles for cancer therapy. © 2011 Springer-Verlag Berlin Heidelberg