"Nano- Biotechnological Advances For Diabetic Wound Healing 52011, 280). The main reason for all this is that oxidation mainly impairs the ability the threecell types to restore the skin and wound healing.Engineered Nanoceria in tests has been foundto facilitate the proliferation of the cultured microvascular endothelial cells, fibroblasts andthe keratinocytes and all the migration of all these. As known the three cells receive a lot ofsignals from different cells in the human body, and additionally the extracellular matrix cuesthat happen during the wound healing process.Nanoceria enhances the infiltration of theleukocytes in the first days of the injury to the skin. Recently, cerium (Ce) oxide nanoparticles (CNPs) have been developed and are beingused as antioxidants. CNPs have a characteristic low reduction potential and is also knownfor the coexistence of both Ce(3+)/Ce(4+) on their surfaces. The function of these newlydeveloped nanoparticles can largely depend on the microenvironment. Their unique propertylies in the fact that their valence states are mixed. CNPs can be utilized for the handling ofchronic oxidative stress and inflammation (Zhang et al., 2014, 377). The initial tests that havebeen conducted on them gave quite impressive results. The organic compounds which are used for disinfection have a few limitations likecausing toxicity to the human body. It leads to the growing interest in chemical disinfectantslike metal oxide nanoparticles (NPs). Nanoparticles with some surface modifications canshow good antimicrobial activity. These antibacterial agents can destroy bacteria in itslocation, without being toxic to other tissues in the surrounding. Standard antibacterials are ß- lactams (like penicillins), cephalosporins or carbapenems. Apart from these,aminoglycosides, or even purely, synthetic antibiotics like sulphonamides can be used assuitable antimicrobial agents. These agents can be broadly classified into two distinct groups:as either bactericidal, which kill bacteria, or bacteriostatic, which slows down bacterialgrowth. The only challenge that antimicrobials face in the modern era is that due to their use Nano- Biotechnological Advances For Diabetic Wound Healing 6and abuse, bacterial resistance has been developed towards antibacterial drugs. Thisphenomenon is quite common nowadays.The resistance that is generated during the antimicrobial treatment process isinheritable resistance in most cases. Gene is transferred by conjugation, transduction ortransformation in bacteria. Apart from these, several side effects of antimicrobial agents havealso been noticed. Drug resistance enforces a higher dose of antibiotics, resulting inintolerable toxicity. It led to the creation of a variety of antimicrobial nanoparticles. It can beeffective in treating infectious diseases and even the ones involving antibiotic-resistance.They have a large surface area to the volume ratio. Antibacterial used for bacteria are highlyspecific to the particular bacterial strains. Extracellular Matrices nanoparticles The extracellular matrix (ECM) is noticeably a large-sized component of the humanskin. The production of ECM is necessary for wound healing. The cutaneous ECM is madeup of a complex assortment of the proteins that was initially believed to be the cause of themechanical resistance and the scaffolding characteristics of it (Ghazi et al., 2012, 487).However, recent development has shown that the ECM‘s functions are more than all these(Falcao, 2012, 32). They include delivery and storage of the growth factors and cytokines,various psychological functions and the repairmen of the tissues. When there is an unusualECM reconstruction during the process of healing of the wound, it leads to the contribution ofthe forming of the hypertrophic and keloid scars (Maruyama et al., 2007, 1179). The recentdevelopment in the wound healing process would desire the reduction of protease amount influids of the in the injury as this will be beneficial for healing of the wound. The process canbe executed by providing a competitive substrate (collagen) for the proteases and hence lower Nano- Biotechnological Advances For Diabetic Wound Healing 7proteolytic annihilation of very important ECM components and growth factors that arederived from the platelets (PDGFs). ECM carries a major role in injury curing and that the ruin or lowering of ECMcomponents deters healing. The skin is somehow elastic and at the same time is alsounyielding due to the amalgamation of two groups of ECM molecules.These are fibrousauxiliary proteins that hand the ECM quality and strength. Proteoglycans, which have variousglycosaminoglycan chains which branch from a straight protein center. Extracellularproteoglycans are large structures that protect cells in ECM. Reduction in the annihilation ofECM or rebuilding of some undamaged ECM is an essential part of the injury healing processof current drugs. In diabetic patients, due to several factors, wound healing is impaired.Expression of FN, CS, and TN was detected in dermal tissue early in normal wound healing.These data show that many substantial differences exist in the cellular infiltrate as well asECM expression patterns of acute, healing versus chronic wounds. The later may be linked tothe nonhealing status of chronic wounds. Matrix Metalloproteinases) are a kind of zincendopeptidases that have the capability of corrupting all components of the extracellularmatrix. Experiments carried out by comparing punch biopsies obtained from the chronic ulcermargins and control samples collected from upper leg skin B cells, and plasma cells weredetected in both type of chronic wound. The comparison was based on acute wound healingmodel (Li, Chen & Kirsner, 2007, 17). ECM contains a group of matrix proteins. Any imbalance of these matrix proteins orany other of their inhibitors may cause degradation of the matrix. ECM degradation is acomplex process and is needed to be controlled; thus an imbalance between ECM formationand the degradation process could lead to the development of chronic ulcers or fibrosis, it isnecessary to restore the balance between the ECM and degradation enzymes. Nano- Biotechnological Advances For Diabetic Wound Healing 8Astragaloside IV diabetic wound healingAstragaloside IV (AS-IV), is one of the active compounds that is mainly extractedfrom the Astragali Radix. In recent research about (AS-IV), it‘s been seen to be anti- inflammatory and produces immunoregulatory activities to the human body (Wood et al.,2014, e91574). AS-IV has been found to promote wound repair in people with diabetes asrecent experiments have shown that it resulted in the wounds gaping narrower and showingcharacteristics of augmented re-epithelization (Xing, Chen, and Zhong, 2005, 141). The mainreason for all these is that AS-IV enhanced the deposition of collagen Illa, which suggests adirect effect of the AS-IV on the synthesis of the matrix (Daly, 2011, 211). The AS-IVimproves the new formation of the vessels of the blood in the wound tissue by increasing thenumber of those of the endothelial cells and also the enhanced expression of the vWF andVEGF. AS-IV also results in the creation of the polarized macrophages, which are mainlyinvolved in the stopping or suppression of the inflammation, thus the facilitation of woundrepair (Zhang et al., 2011, 486). Thus, recent researches on the AS-IV show that it plays avery crucial role in the maintenance of the cutaneous homeostasis and the accelerated healingof the wounds in people with diabetes. The main for all this is that diabetes leads to delayedwound healing along with chronic ulcer formation which can result in several complicationslike infection and gangrene. Healing of diabetic wounds is impaired by factors likedysregulated leukocyte chemotaxis, some, extracellular matrix deposition, and fibroblastmigration.Many times, phagocytosis of the cells also lead to impaired healing.Neovascularization can be decreased in hyperglycemia; this supports the impairment ofwound healing in patients with diabetes.Gum-Tragacanthin, Polycaprolactone (GT) (PCL/GT) Nanofibers Nano- Biotechnological Advances For Diabetic Wound Healing 9Wound healing can further be made more fast and efficient with the correctapplication of the gum tragacanthin (GT) and the use of poly (e-caprolactone) (PCL) in eitherskin tissue engineering or the application of wound dressing. The addition of GT andcurcumin in proper ratios led to the increase in the hydrophilicity of the nanofibers withsuitable mechanical properties along with their excellent biological characteristics. Thesescaffolds with antibacterial property were experimented upon by keeping them exposed tomany microbial species and then testing their durability. Application of GT/PCL/Curnanofibers result in fast wound closure Also, collagen deposition formation of sweat glandsare noticed. It was seen that the addition of curcumin to the PCL/GT led to the improvementof mechanical properties of the electro spun Nano fibrous (Choi, Leong, and Yoo, p588,2008). Presence of curcumin in the nanofibers improved their stability toward degradationFuture Challenges and TrendsWound healing and its management is a constantly evolving discipline. Ourunderstanding of the pathophysiology has always been continually increasing, but it is notdoing the same at such a rate when it comes to the clinical treatment of the wounds.However, significant trends have emerged in a bid to improve the clinical treatment of theinjuries. Existing products and technologies though have dimmed the dark light on theclinical treatment to some extent. There have been a lot of progress in technology thatincorporates the use of artificial skin products, stem cell therapy and gene therapy,extracellular matrix substitutes and even electrical stimulation. However, one of the mostsuccessful technologies that have come up in the current trends is the Topical NegativePressure (TNP) principle (Goldman, 2004, 25). The therapy us is facilitated by theapplication of the suction across a sealed wound mainly used with a reticulated foam surface.As a result, the suction that is typically generated on the wound surface will at most timesinitiate changes that will impact positively in the healing of the wound."