Tailor-Made Polysaccharides for Biomedical Applications.

Polysaccharides (PSAs) are carbohydrate-based macromolecules widely used in the biomedical field, either in their pure form or in blends/nanocomposites with other materials. The relationship between structure, properties, and functions has inspired scientists to design multifunctional PSAs for various biomedical applications by incorporating unique molecular structures and targeted bulk properties. Multiple strategies, such as conjugation, grafting, cross-linking, and functionalization, have been explored to control their mechanical properties, electrical conductivity, hydrophilicity, degradability, rheological features, and stimuli-responsiveness. For instance, custom-made PSAs are known for their worldwide biomedical applications in tissue engineering, drug/gene delivery, and regenerative medicine. Furthermore, the remarkable advancements in supramolecular engineering and chemistry have paved the way for mission-oriented biomaterial synthesis and the fabrication of customized biomaterials. These materials can synergistically combine the benefits of biology and chemistry to tackle important biomedical questions. Herein, we categorize and summarize PSAs based on their synthesis methods, and explore the main strategies used to customize their chemical structures. We then highlight various properties of PSAs using practical examples. Lastly, we thoroughly describe the biomedical applications of tailor-made PSAs, along with their current existing challenges and potential future directions.

Polysaccharide-based nanocomposites for biomedical applications: a critical review.

Polysaccharides (PSA) have taken specific position among biomaterials for advanced applications in medicine. Nevertheless, poor mechanical properties are known as the main drawback of PSA, which highlights the need for PSA modification. Nanocomposites PSA (NPSA) are a class of biomaterials widely used as biomedical platforms, but despite their importance and worldwide use, they have not been reviewed. Herein, we critically reviewed the application of NPSA by categorizing them into generic and advanced application realms. First, the application of NPSA as drug and gene delivery systems, along with their role in the field as an antibacterial platform and hemostasis agent is discussed. Then, applications of NPSA for skin, bone, nerve, and cartilage tissue engineering are highlighted, followed by cell encapsulation and more critically cancer diagnosis and treatment potentials. In particular, three features of investigations are devoted to cancer therapy, i.e., radiotherapy, immunotherapy, and photothermal therapy, are comprehensively reviewed and discussed. Since this field is at an early stage of maturity, some other aspects such as bioimaging and biosensing are reviewed in order to give an idea of potential applications of NPSA for future developments, providing support for clinical applications. It is well-documented that using nanoparticles/nanomaterials above a critical concentration brings about concerns of toxicity; thus, their effect on cellular interactions would become critical. We compared nanoparticles used in the fabrication of NPSA in terms of toxicity mechanism to shed more light on future challenging aspects of NPSA development. Indeed, the neutralization mechanisms underlying the cytotoxicity of nanomaterials, which are expected to be induced by PSA introduction, should be taken into account for future investigations.

Polylysine for skin regeneration: A review of recent advances and future perspectives.

There have been several attempts to find promising biomaterials for skin regeneration, among which polylysine (a homopolypeptide) has shown benefits in the regeneration and treatment of skin disorders. This class of biomaterials has shown exceptional abilities due to their macromolecular structure. Polylysine-based biomaterials can be used as tissue engineering scaffolds for skin regeneration, and as drug carriers or even gene delivery vectors for the treatment of skin diseases. In addition, polylysine can play a preservative role in extending the lifetime of skin tissue by minimizing the appearance of photodamaged skin. Research on polylysine is growing today, opening new scenarios that expand the potential of these biomaterials from traditional treatments to a new era of tissue regeneration. This review aims to address the basic concepts, recent trends, and prospects of polylysine-based biomaterials for skin regeneration. Undoubtedly, this class of biomaterials needs further evaluations and explorations, and many critical questions have yet to be answered.

Polysaccharide-based electroconductive hydrogels: Structure, properties and biomedical applications.

Architecting an appropriate platform for biomedical applications requires setting a balance between simplicity and complexity. Polysaccharides (PSAs) play essential roles in our life in food resources, structural materials, and energy storage capacitors. Moreover, the diversity and abundance of PSAs have made them an indispensable part of food ingredients and cosmetics. PSA-based hydrogels have been extensively reviewed in biomedical applications. These hydrogels can be designed in different forms to show optimum performance. For instance, electroactive PSA-based hydrogels respond under an electric stimulus. Such performance can be served in stimulus drug release and determining cell fate. This review classifies and discusses the structure, properties, and applications of the most important polysaccharide-based electroactive hydrogels (agarose, alginate, chitosan, cellulose, and dextran) in medicine, focusing on their usage in tissue engineering, flexible electronics, and drug delivery applications.

Chitosan-based blends for biomedical applications.

Polysaccharides are the most abundant naturally available carbohydrate polymers; composed of monosaccharide units covalently connected together. Chitosan is the most widely used polysaccharides because of its exceptional biocompatibility, mucoadhesion, and chemical versatility. However, it suffers from a few drawbacks, e.g. poor mechanical properties and antibacterial activity for biomedical applications. Blending chitosan with natural or synthetic polymers may not merely improve its physicochemical and mechanical properties, but may also improve its bioactivity-induced properties. This review paper summarizes progress in chitosan blends with biodegradable polymers and polysaccharides and their biomedical applications. Blends of chitosan with alginate, starch, cellulose, pectin and dextran and their applications were particularly addressed. The critical and challenging aspects as well as the future ahead of the use of chitosan-based blends were eventually enlightened.

Injectable Cell-Laden Hydrogels for Tissue Engineering: Recent Advances and Future Opportunities.

Tissue engineering intends to create functionalized tissues/organs for regenerating the injured parts of the body using cells and scaffolds. A scaffold as a supporting substrate affects the cells' fate and behavior, including growth, proliferation, migration, and differentiation. Hydrogel as a biomimetic scaffold plays an important role in cellular behaviors and tissue repair, providing a microenvironment close to the extracellular matrix with adjustable mechanical and chemical features that can provide sufficient nutrients and oxygen. To enhance the hydrogel performance and compatibility with native niche, the cell-laden hydrogel is an attractive choice to mimic the function of the targeted tissue. Injectable hydrogels, due to the injectability, are ideal options for in vivo minimally invasive treatment. Cell-laden injectable hydrogels can be utilized for tissue regeneration in a noninvasive way. This article reviews the recent advances and future opportunities of cell-laden injectable hydrogels and their functions in tissue engineering. It is expected that this strategy allows medical scientists to develop a minimally invasive method for tissue regeneration in clinical settings. Impact statement Cell-laden hydrogels have been vastly utilized in biomedical application, especially tissue engineering. It is expected that this upcoming review article will be a motivation for the community. Although this strategy is still in its early stages, this concept is so alluring that it has attracted all scientists in the community and specialists at academic health centers. Certainly, this approach requires more development, and a bunch of crucial challenges have yet to be solved. In this review, we discuss this various aspects of this approach, the questions that must be answered, the expectations associated with it, and rational restrictions to develop injectable cell-laden hydrogels.

Agarose-based biomaterials for advanced drug delivery.

Agarose is a prominent marine polysaccharide representing reversible thermogelling behavior, outstanding mechanical properties, high bioactivity, and switchable chemical reactivity for functionalization. As a result, agarose has received particular attention in the fabrication of advanced delivery systems as sophisticated carriers for therapeutic agents. The ever-growing use of agarose-based biomaterials for drug delivery systems resulted in rapid growth in the number of related publications, however still, a long way should be paved to achieve FDA approval for most of the proposed products. This review aims at a classification of agarose-based biomaterials and their derivatives applicable for controlled/targeted drug delivery purposes. Moreover, it attempts to deal with opportunities and challenges associated with the future developments ahead of agarose-based biomaterials in the realm of advanced drug delivery. Undoubtedly, this class of biomaterials needs further advancement, and a lot of critical questions have yet to be answered.

Zeolites for theranostic applications.

Theranostic platforms bring about a revolution in disease management. During recent years, theranostic nanoparticles have been utilized for imaging and therapy simultaneously. Zeolites, because of their porous structure and tunable properties, which can be modified with various materials, can be used as a delivery agent. The porous structure of a zeolite enables it to be loaded and unloaded with various molecules such as therapeutic agents, photosensitizers, biological macromolecules, MRI contrast agents, radiopharmaceuticals, near-infrared (NIR) fluorophores, and microbubbles. Furthermore, theranostic zeolite nanocarriers can be further modified with targeting ligands, which is highly interesting for targeted cancer therapies.

Mesenchymal Stem Cell Spheroids Embedded in an Injectable Thermosensitive Hydrogel: An In Situ Drug Formation Platform for Accelerated Wound Healing.

The ability of mesenchymal stem cells (MSCs) to enhance cutaneous wound healing has been well established. Extensive expansion of cells to reach sufficient cell numbers for regenerating tissues has always limited cell-based therapies. An ingenious solution to address this challenge is to develop a strategy to increase the immunomodulatory effects of MSCs without expanding them. In this study, we employed a simple characteristic of cells. It was observed that an optimized three-dimensional (3D) MSC culture in spheroid forms significantly improved their paracrine effects. An electrospray (ES) encapsulation apparatus was used to encapsulate individual or 3D spheroid MSCs into microscale alginate beads (microbeads). Furthermore, alginate microbeads were embedded in an injectable thermosensitive hydrogel matrix, which gels at skin temperature. The hydrogel fills and seals the wounds cavities, maintains high humidity at the wound area, absorbs exudate, and fixes microbeads, protecting them from direct contact with the harsh wound environment. In vitro investigations revealed that secretion of interleukin 10 (IL-0) and transforming growth factor ß1 (TGF-ß1) gene was gradually enhanced, providing a delivery platform for prolonged release of bioactive molecules. In vivo study on full-thickness wounds showed granulation and re-epithelialization, only after 7 days. Moreover, increased expression of α-smooth muscle actin (α-SMA) in the first 14 days after treatment ensured wound contraction. Besides, a gradual decrease in α-SMA secretion resulted in reduced scar formation. Well-organized collagen fibrils and high expression of the angiogenesis biomarker CD31 confirmed the promoting effect of the hydrogel on the wound-healing process. The proposed wound-dressing system would potentially be used in scalable and effective cell-based wound therapies.