LONG CHAIN POLYMERIC CARBOHYDRATE DEPENDENT NANOCOMPOSITES IN TISSUE ENGINEERING

Muhammad Shahzad Aslam

School of Traditional Chinese Medicine, Xiamen University Malaysia, Jalan Sunsuria, Bandar Sunsuria, 43900 Sepang, Selangor

ABSTRACT

The use of nanomedicine has increased enormously, especially in the field of gene delivery and targeted drug delivery. The objective of current review to identify long-chain polymeric carbohydrate dependent nano-composites in tissue engineering such Gellan gum incorporated TiO2 nanotubes, Poly(vinyl) alcohol-gellan gum-based nanofiber, Cross-linked gellan/PVA nanofibers, Nanocellulose reinforced gellan-gum hydrogels, Dextran and sol-gel derived bioactive glass-ceramic nanoparticles, Aminated β-Cyclodextrin-Modified-Carboxylated Magnetic Cobalt/ Nanocellulose Composite, Chitosan-chitin nanocrystal composite scaffolds, Sodium alginate-xanthan gum-based nano-composite scaffolds, Nano-hydroxyapatite  Pullulan/dextran polysaccharide composite, Chitosan/Carbon nanofibers Scaffolds, Nano-bio composite scaffold of chitosan–gelatin–alginate–hydroxyapatite, Alginate/gelatin scaffolds with homogeneous nano apatite coating,Nano-hydroxyapatite-alginate-gelatinmicrocapsule,Poly(ε-caprolactone)/keratin nano fibrousmats, Keratin nanoparticles-coating electrospun PVA nanofiber, Nano-hydroxyapatite/chitosan/chondroitin sulfate/hyaluronic acid and Chitosan/chondroitin sulfate/nano-bioglass. The current review has identified a list of medicinal herbs that have been incorporated into long chain polymeric carbohydrate-based nano-composites

Keywords: Nano-composites, nanomedicine, polymeric carbohydrate.

 

INTRODUCTION

Nanomedicine has gained a lot of interest due to its vast application. Physical and chemical attributes of nanomaterials have lengthened its application in the field of biological science and biomedical engineering such as biological imaging, drug delivery, biomolecular sensing, and Infectious Diseases1.  There are different types of nanomaterials such as Inorganic nanomaterials (Graphene, mesoporous silica, gold, magnetic, quantum dots, and layered double hydroxides) and metal-organic frameworks (Zirconium -based metal-organic frameworks, Lanthanide-Based Metal-Organic Frameworks, Oligo nucleotide - Functionalized Metal-Organic Framework)2,3. Inorganic nano materials possess intrinsically physicochemical properties and good biocompatibility, as a result, they are used in different applications such as bio imaging, targeted drug delivery, and cancer therapies, whereas the Metal-organic framework is porous hybrid polymer-metal composites4,5. They possess many biomedical applications due to their excellent porosity, high loading capacity, biodegrade-bility, and ease of surface modification when compared to others6,7.

The selection of material depends upon the biological activity, biocompatibility, and biodegradability. The materials provide an analogous environment to the extracellular matrix (ECM) and provide an induced rate of synthesis or growth of new tissues. Extracellular matrix consists of collagen fibril, glycoproteins such as fibronectin and laminin for attachment. In addition to the extracellular matrix, connective tissues are characterized by fibroblasts and ground substances which are usually fluid, but it can also be mineralized and solid, as in bones8. Polysaccharides offer a green alternative to synthetic polymers in the preparation of soft nanomaterials9.Monosaccharides and disaccharides are bonded through covalent linkage to develop a long chain of polymer-based carbohydrates. They also consist of other functional groups such as pyruvate, sulfate, and methyl. They can range from linear to branched structure. A list of bacterial polysaccharides consists of the intracellular, capsular, or exo-based skeleton. Exo based polysaccharides are Dextran, alginate, hyaluronic acid, and xanthan, which are synthesized extracellularly by cell wall-anchored enzymes10,11,12.

Table 1: Long chain polymeric Carbohydrate dependent nano-composites in tissue engineering

Ismail et al., prepared gellan gum incorporated TiO2 nanotubes using the solvent casting method for skin tissue engineering. TiO2 nanotubes are a promising tool for cell growth and proliferation for wound healing13. They are biocompatible osseointegration14 and attenuate inflammatory mediators15. Aadil et al., formulate poly(vinyl) alcohol-gellan gum-based nanofiber using electrospinning and found promising 3D nanofibrous scaffolds for various tissue engineering applications16. Poly (d, l-lactide-co-glycolide acid) (PLGA) nanofiber is an alternative biodegradable polymer when compared with polysaccharide-based nanofiber, which is used in medical devices and drug delivery applications17. Gellan and PVA cross-link nanofiber is prepared to enhance the physicochemical stability and made biocompatible to human dermal fibroblast (3T3L1) cells18. Cellulose nanocrystals offer to aggrandize Cytocomp-atibility and improved mechanical properties as compared to carbon or metallic nanotubes19. Nanocellulose reinforced gellan-gum hydrogelsare helpful in Annulus fibrosus (AF) defects such as annular tears, herniation, and discectomy20. Nanocellulose Composite for also useful in the tumor-targeted gene delivery. Anirudhan and Rejeena have developed a novel non-viral gene vector consists of aminated b-cyclodextrin modified carboxylated magnetic cobalt/nanocellulose composite, which helps reduce the toxicity but also increased the transgene expression level21. Yvette and co-researcher also worked on nanocellulose based gene delivery and designed polyelectrolyte layer assembly of bacterial nanocellulose whiskers with plasmid DNA22. Nguyen et al., developed nanocellulose/ alginate Bioink for 3D Bioprinting of iPS Cells. The result suggests supporting cartilage production in co-cultures with irradiated chondrocytes23. The other researcher also supports the evidence for the development of 3D bioprinting using nanocellulose such as 3D bioprinting of human chondrocyte-laden nanocellulose hydrogels for patient-specific auricular cartilage regeneration24, wood-based nanocellulose and bioactive glass modified gelatin–alginate bioinks for 3D bioprinting of bone cells25 and  development of nanocellulose-based bioinks for 3D bioprinting of Soft Tissue. The problem in all the above research lacks pre-clinical and clinical trials. This leads to motivation for researchers to design a randomized double-blind clinical trial for future commercial prospective. Dextran based hydrogel is prevalent in a different kind of tissue repair such as cartilage tissue engineering26, vascular tissue engineering27, bone tissue engineering28, skin tissue engineering,29, wound repair30. Nikpour and their co researcher-developed Dextran based bioactive glass-ceramic nano-composite scaffold. They synthesized nano bioactive glass-ceramic particles (nBGC) by sol-gel method, whereas the chemical cross-linked technique is used for the preparation of the nano-composite scaffold. They identify silicon dioxide improves surface reaction to contact with body fluids, and develops active surface area for in vitro/vivo bone tissue engineering31. Some important Polysaccharide-based Nano-composites for tissue engineering and gene delivery are mentioned in Table 1. The researcher excluded several nano-composite as of lack of available literature on in-vitro or in-vivo evaluation. Chitosan-based biomaterial has been well known for the preparation of nontoxic, biodegradable, and biocompatible polysaccharide of β(1-4)-linked d-glucosamine and N-acetyl-d-glucosamine32.  Chitosan has been used to prepare collagen/chitosan porous scaffolds33, injectable chitosan-based hydrogels34, chitosan-nanohydroxyapatite composite scaffolds35, chitin-based tubes36, chitosan-alginate hybrid scaffolds37, and chitosan/carbon scaffolds38.

Table 2: Some medicinal herbs incorporated into long-chain polymeric carbohydrate-based nano-composites for tissue regeneration

Medicinal herbs incorporated into long-chain polymeric carbohydrate-based Nano-composites

Plants are the essential foundation of medicine. Some essential drugs that are still in use today are derived from traditional medicinal herbs49. Functional polysaccharides have a wide variety of application in the field of biomedical engineering and tissue repair50. Several medicinal herbs such as Indigofera aspalathoides, Azadira chtaindica, Memecylonedule  and Myristica andamanica, along with a biodegradable polymer, polycaprolactone has been used in combination for skin tissue engineering51. Table 2 represents some of the medicinal herbs that are used in combination with polysaccharides based Nano-composites. Lycium barbarum polysaccharides have encapsulated Poly lactic-co-glycolic acid Nanofibers is indicated for peripheral nerve tissue engineering52. Elaeagnus angustifolia is traditionally indicated in osteoarthritis53. Elaeagnus angustifolia extract was loaded in poly(ɛ-caprolactone)-poly (ethylene glycol)-poly(ɛ-caprolactone) (PCL-PEG-PCL/EA) nanofibers for bone tissue engineering54. Aloe vera is incorporated in poly (ε-caprolactone)/gum tragacanth nanofibers to develop the wound dressing55. Stryphnodendron adstringens is indigenous to Brazil and a well-known wound healing herb on the eastern coast of South America56. It has been used in combination with Polyvinyl alcohol and pineapple nanofibers for medical applications57.

Clinical trials of long-chain polymeric carbohydrate-based Nano-material

Limited available literature on the clinical trial of polysaccharides based Nano-material. Although several material is available and examined in-vitro or in-vivo a very few materials went for the clinical trial. Most of the available literature does not seem able to proceed further for clinical trials.  A pilot randomized clinical trial of a customized nanotextile wet garment treatment was performed on moderate and severe atopic dermatitis and found useful in the treatment of eczema58. A couple of randomized, double-blind clinical trials have been performed on nano-hydroxyapatite toothpaste and nano-hydroxyapatite plus 8% Arginine in dentine hypersensitivity intervention59,60. Table 3 represent clinical trials with polysaccharides based Nano-material.

Table 3: Clinical trials with long-chain polymeric carbohydrate-based Nano-material

CONCLUSION

Polymer-based carbohydrate molecules composed of long strings of simple sugars (i.e., monosaccharides or disaccharides) that are covalently linked together by glycosides. They are readily usable and can be used for development, assembling, and modification. Polysaccharides also provide 'natural' alternatives to oil-based synthetic polymers.The creation of nanoparticles from polysaccharides is accomplished by ion or covalent cross-linking, ion-complex, and self-assembly following the grafting of the hydrophobic segments onto the polymer backbone. Polymeric chain length and their charges are an important factor in the selection of appropriate methodology for the development of new nanoparticles.

 

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