The use of physical hydrogels of chitosan for skin regeneration following third-degree burns

Advances in hydrogel technology have unlocked unique and valuable capabilities that are being applied to a diverse set of translational applications. Hydrogels perform functions relevant to a range of biomedical purposes-they can deliver drugs or cells, regenerate hard and soft tissues, adhere to wet tissues, prevent bleeding, provide contrast during imaging, protect tissues or organs during radiotherapy, and improve the biocompatibility of medical implants. These capabilities make hydrogels useful for many distinct and pressing diseases and medical conditions and even for less conventional areas such as environmental engineering. In this review, we cover the major capabilities of hydrogels, with a focus on the novel benefits of injectable hydrogels, and how they relate to translational applications in medicine and the environment. We pay close attention to how the development of contemporary hydrogels requires extensive interdisciplinary collaboration to accomplish highly specific and complex biological tasks that range from cancer immunotherapy to tissue engineering to vaccination. We complement our discussion of preclinical and clinical development of hydrogels with mechanical design considerations needed for scaling injectable hydrogel technologies for clinical application. We anticipate that readers will gain a more complete picture of the expansive possibilities for hydrogels to make practical and impactful differences across numerous fields and biomedical applications.

Translational Applications of Hydrogels.

Tissue engineering uses a combination of cell biology, chemistry, and biomaterials to fabricate three dimensional (3D) tissues that mimic the architecture of extracellular matrix (ECM) comprising diverse interwoven nanofibrous structure. Among several methods for producing nanofibrous scaffolds, electrospinning has gained intense interest because it can make nanofibers with a porous structure and high specific surface area. The processing and solution parameters of electrospinning can considerably affect the assembly and structural morphology of the fabricated nanofibers. Electrospun nanofibers can be made from natural or synthetic polymers and blending them is a straightforward way to tune the functionality of the nanofibers. Furthermore, the electrospun nanofibers can be functionalized with various surface modification strategies. In this review, we highlight the latest achievements in fabricating electrospun nanofibers and describe various ways to modify the surface and structure of scaffolds to promote their functionality. We also summarize the application of advanced polymeric nanofibrous scaffolds in the regeneration of human bone, cartilage, vascular tissues, and tendons/ligaments.

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Current progress in application of polymeric nanofibers to tissue engineering.

Carboxymethyl cellulose-based materials for infection control and wound healing: A review.

The universal increase in the number of patients with nonhealing skin wounds imposes a huge social and economic burden on the patients and healthcare systems. Although, the application of traditional wound dressings contributes to an effective wound healing outcome, yet, the complexity of the healing process remains a major health challenge. Recent advances in materials and fabrication technologies have led to the fabrication of dressings that provide proper conditions for effective wound healing. The 3D-printed wound dressings, biomolecule-loaded dressings, as well as smart and flexible bandages are among the recent alternatives that have been developed to accelerate wound healing. Additionally, the new generation of wound dressings contains a variety of microelectronic sensors for real-time monitoring of the wound environment and is able to apply required actions to support the healing progress. Moreover, advances in manufacturing flexible microelectronic sensors enable the development of the next generation of wound dressing substrates, known as electronic skin, for real-time monitoring of the whole physiochemical markers in the wound environment in a single platform. The current study reviews the importance of smart wound dressings as an emerging strategy for wound care management and highlights different types of smart dressings for promoting the wound healing process.

Wound Healing: From Passive to Smart Dressings.

Commercial hydrogels for biomedical applications.

Artificial skin substitute made of polymeric films are of great demand in the field of skin tissue engineering. We report here the fabrication of carboxymethyl cellulose (CMC) and poly(ethylene glycol) (PEG) blend films by solution casting method for wound healing applications. The physicochemical characteristics and the thermal stability of the films were analyzed. The surface morphology shows crystalline structures with large hexagonal-like platelet crystals of CMC on the surface of the films. Pure CMC films exhibited higher tensile strength than the CMC/PEG blend films. The swelling ratio (SR) of the films was influenced by the pH of Tris–HCL buffer (2.0, 5.0, and 7.0), which increased with increase in pH. The hemocompatibility assay and cytotoxicity test using NIH 3T3 fibroblast cells showed that the films were biocompatible. To evaluate the wound healing efficacy, the films were applied in full-thickness wounds created in normal and diabetic Wistar albino rats. The wounds healed faster with pure CMC ...

Characterization and Evaluation of Carboxymethyl Cellulose-Based Films for Healing of Full-Thickness Wounds in Normal and Diabetic Rats.

PEO–CMC blend nanofibers fabrication by electrospinning for soft tissue engineering applications

The present study involves the development of citric acid-cross-linked carboxymethyl cellulose (C3CA) scaffolds by a freeze-drying process. Scaffolds were fabricated at different freezing temperatures of -20, -40, or -80 °C to investigate the influence of scaffold pore size on bone regeneration. All three scaffolds were porous in structure, and the pore size was measured to be 74 ± 4, 55 ± 6, and 46 ± 5 μm for -20, -40, and -80 °C scaffolds. The pores were larger in scaffolds processed at -20 °C compared to -40 and -80 °C, indicating the reduction in pore size of the scaffolds with a decrease in freezing temperature. The cytocompatibility, cell proliferation, and differentiation in C3CA scaffolds were assessed with the Saos-2 osteoblast cell line. These scaffolds supported the proliferation and differentiation of Saos-2 cells with significant matrix mineralization in scaffolds processed at -40 °C. Subcutaneous implantation of C3CA scaffolds in the rat model was investigated for its ability of vascularization and new matrix tissue formation. The matrix formation was observed at the earliest of 14 days in the scaffolds when processed at -40 °C while it was observed only after 28 days of implantation with the scaffolds processed at -20 and -80 °C. These results suggest that the citric acid-cross-linked CMC scaffolds processed at -40 °C can be promising for bone tissue engineering application.

In Vitro and In Vivo Evaluation of Carboxymethyl Cellulose Scaffolds for Bone Tissue Engineering Applications.

Injectable calcium phosphate cement is a promising biomaterial for hard tissue repair due to its osteoinductivity, biocompatibility properties, and its use to correct defect areas involving narrow cavities with limited accessibility by the minimally invasive technique. Microwave-synthesized hydroxyapatite (HA) was used for the preparation of cement. In recent years, both magnesium and strontium calcium phosphate cements have exhibited rapid setting, improved mechanical strength, and a good resorption rate. A big step still remains to develop injectable magnesium and strontium phosphate cements with ideal self-setting properties, adequate mechanical strength, and good biocompatibility for clinical applications. In this study, both magnesium and strontium were doped with synthesized semiamorphous and crystalline hydroxyapatite (HA). The powder mixture was mixed with Na2HPO4, NaH2PO4, and a carboxymethyl cellulose (CMC) solution to develop the novel magnesium and strontium calcium phosphate cement. The setting time, physiochemical properties of hardened cement, microstructure, mechanical strength, and injectability of the prepared cement were studied. The toxicity evaluation and cell adhesion, which are necessary to identify the suitability of the material for different applications, were quantified and investigated using fibroblast cells. The setting time of cement was reduced substantially for magnesium- or strontium-doped cement by 2 min. The phase composition of the hardened cement expresses the semiamorphous or crystalline phase of HA with additives. Smooth and complete injection of cement paste was observed in semiamorphous HA-based cement. The intercellular reactive oxygen stress (ROS) of the Sr2+-doped cement sample showed varied degrees of toxicity to cells in terms of different concentrations. The Mg2+-doped cement showed significant attachment of cells after treatment at varying incubation times.

U. Narendrakumar

Papers

Commercial hydrogels for biomedical applications.

Characterization and Evaluation of Carboxymethyl Cellulose-Based Films for Healing of Full-Thickness Wounds in Normal and Diabetic Rats.

PEO–CMC blend nanofibers fabrication by electrospinning for soft tissue engineering applications

In Vitro and In Vivo Evaluation of Carboxymethyl Cellulose Scaffolds for Bone Tissue Engineering Applications.

Characterization and In Vitro Evaluations of Injectable Calcium Phosphate Cement Doped with Magnesium and Strontium.