Nanomaterials for Biomedical Applications: History
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As the human population ages and the future expands, tissue wounds and pathophysiology will keep on expanding, imposing a real physical and money-related strain on the overall social insurance frameworks. To this end, it is foreseen that biomaterial NPs will offer the best way to deal with regenerative medicine that will assume an urgent role in the regeneration of damaged body parts. It is believed that the field of bioactive nanomaterials will keep on exponentially developing in the future, given the examples of overcoming limitations of biomaterial approaches in scholastic, clinical and mechanical-based procedures. The US market is expected to show increased expenses for bioactive nanomaterial supplies from USD 70.03 billion to USD 130.17 billion before the end of 2021, with a growth rate of 13.2%. Nanomaterials that can be classified as bioactive nanomaterials are divided into two categories according to their origin, either natural or synthetic nanomaterials.

  • Nanomaterials
  • drug delivery systems
  • Biomaterials

1. Regenerative Medicine

Tissue malfunctioning has become a noteworthy medical issue in the United States and most other geographical areas around the world. It was reported that only the United States has around 89000 patients who need tissue or organ transplantation [1]. Recently, a brilliant interdisciplinary field was able to solve the issue of tissue and organ replacement, which is called nanomedicine. Nanomedicine provides nanomaterials that can be used as a substrate for cell growth and proliferation and can deliver medicine and biological molecules, which eventually results in new tissue or organ replacing the damaged body part under controlled conditions [2]. Among the various nanomedicine techniques is the guided regeneration technique, where synthetic biodegradable nanoplatforms like poly(L-lactic acid) (PLLA), polyglycolic acid (PGA), poly(D,L-lactide-co-glycolide) (PLGA), polycaprolactone (PCL), polyphosphazenes, etc., are used for directing cell growth [3][4][5][6][7].

Moreover, nerve generation is one of the most significant issues in regenerative medicine. Till now, it is a significant challenge to recover nerve tissue at injury sites. There are different types of nanomaterials that have been created and are under study to prevent or treat nerve damage. Many of the nanomaterials are promising, with appropriate physicochemical properties, and have been subsequently used for neural tissue regeneration applications. These have shown promising outcomes that can help cell attachment and expansion, advance neuronal cell separation and upgrade the recovery of neurons [7]. Some inorganic materials have been used in the regeneration of damaged nerves, such as metallic NPs [6], silica NPs [7], magnetic NPs [8] and quantum dots [9]. On the other hand, distinctive organic nanomaterials have been studied for neural tissue regeneration applications [10]. Polymeric NPs [11], liposomes [12], dendrimers [13], micelles [14], nanofibres [15] and carbon-based nanomaterials [16] are some natural nanomaterials.

In addition, the use of nanomaterials may be an appropriate solution since these materials can mimic the surface properties of damaged tissue. Consequently, in the past decades, nanomaterials have been featured as promising candidates for improving conventional tissue regeneration materials. Critically, these endeavours have shown that nanomaterials display unrivalled cyto-compatible, electrical, mechanical, synergist, optical and attractive properties compared with traditional materials. These impressive properties of nanomaterials have assisted in improving different tissue developments over what is reachable today. Nanomaterials have been proved useful for bone [17], ligament [18], vascular [19] and bladder tissue [20] regeneration applications as well.

Moreover, it is worth highlighting that wound treatments that adopt regenerative medicine approaches are becoming very popular. Humans are subjected to different wound impacts that may result from several causes. If this is to be defined on a biological basis, it would be when a person is injured. However, four major steps are involved in the evolution of a wound: haemostasis, inflammation, proliferation and maturation [21][22][23][24]. In the treatment of wounds, many approaches were developed during the last five decades. Among these approaches, nanotechnology had gained great attention among the scientists interested in this field. In addition, great preference was given to the inclusion of inorganic agents in these medication devices as antibacterial agents, such as Zn, Ag, Cu and others; loading of antibiotics in nanomaterials was also explored [24]. The usage of these NPs loaded with antibacterial agents or antibiotics is demonstrated to be the best aid in the treatment of wounds. Nanofibres loaded with bioactive molecules, drugs and antibacterial agents are considered as one type of polymer nanomaterials. They have exhibited incredible results when used as skin regeneration materials or patches [25][26].

Electrospinning has been generally used as a nanofibre manufacturing method. Its basic procedure, cost viability and adaptability have been recognised by materials researchers universally. Unblemished polymeric nanofibres or composite nanofibres with unique morphologies and multidimensional congregations going from one-dimensional (1D) to three-dimensional (3D) can be acquired from electrospinning. Basically, these nanofibres have a greater surface-area-to-volume ratio, tuneable porosity and simple surface functionalisation, which present various opportunities for applications, especially in the biomedical field. These are some ongoing advances in electrospinning-based nanomaterials for biomedical applications, for example, antibacterial mats [27], patches for quick haemostasis [28], wound dressings [29] and scaffolds for skin regeneration [30][31].

A few principles should be applied in the scale-up (large-scale) production of nanomaterials for the biomedical field. Among these principles, the quality-by-design (QbD) principle has been used normally in industrial applications such as car manufacturing. For example, it is well known that patient satisfaction is based on the characteristics of nanomaterials, like minimal side effects. At this point, the role of QbD is to remove unwanted side effects from the nanomaterials delivered to the market. There must be a coordinated arrangement between individuals belonging to the industrial sector and scientists; a fruitful group must start with obviously verbalised shared objectives for the item that are quantifiable and approved by healthcare authorities.

2. Drug and Gene Delivery Systems

Sustained drug delivery in a prolonged manner is desired in numerous situations to achieve enhanced results and enhanced patient consistence; that is why scientists prefer NPs as drug carriers. Numerous research articles have proven this concept. For example, an in vivo study on diabetic rodents demonstrated that subcutaneously infused insulin-stacked polymeric NPs of 85–185 nm size had a longer hypoglycaemic impact than free insulin [3]. In another examination, intramuscularly administered 600 nm PLGA NPs stacked with plasmid DNA demonstrated continued quality delivery [5].

Targeted medication conveyance stands out amongst the most sought-after objectives in medication quality. NPs are fit for focusing on a broad range of stages, from cells to tissues to organs, especially for organelles present in the cells. In general, each tissue and organ has its own transportation mechanism, with a specific size, and most of the time, these transportation mechanisms are different for each tissue and organ. Therefore, targeting a specific tissue or organ can be done by adjusting the particle size, shape and surface functionalisation properties. For instance, veins in the liver contain fenestrations of around 106–175 nm [5]. These organs canthus be specifically targeted by controlling the size and surface properties of the NPs. Numerous kinds of tumours are characterised by permeable veins. The pore cut-off measures these veins somewhere in the range of 380 and 780 nm. Flowing NPs somewhere in the range of 100 and 300 nm would, along these lines, spill through the pores and gather in the tumour due to the enhanced permeability and retention (EPR) effect [5]. In addition, by appending ligands, NPs can effectively target, for all intents and purposes, any sort of available cells with distinguished cell receptors.

To overcome these issues and enhance the remedial impact of cisplatin (CDDP), very specific a supra-portion intra-blood vessel CDDP mixture for cutting-edge Head and neck squamous cell carcinoma (HNSCC) was applied [32]. However, since this method is more confusing than implantation of anti-tumour medications, it is not pervasive in the chemotherapy scene. Of late, a few types of nanoparticle restorative stages, including liposomes, NPs and polymeric micelles, have been created depending on the possibility that the drug delivery system (DDS) can be delivered specifically to the tumour, with decreased circulation in typical tissues and limited undesirable side effects [32][33][34][35]. NC-6004, which is a CDDP-joining polymeric micellar nanoparticle, upgraded anti-tumour movement and diminished the nephrotoxicity and neurotoxicity of CDDP in gastric cancer [36][37][38]. It is a long, well-established reality that a decrease per unit volume of a material builds the surface territory of the material. This essential idea is substantial for medication conveyance advancements using nanoscale elements. When contrasted with regular medication conveyance frameworks, nanotechnology-based medication conveyance frameworks have enhanced surface zones. This expanded surface region per unit volume enhances the stacking and discharging effectiveness of medications.

The nanotechnology-based medication conveyance level provides analysts with choices to deliver exceedingly poisonous medication intermediates and edifices and, in addition, DNA and viral vectors at ideal measurements at controlled interims of time [39]. The release behaviour from materials relies to a great extent on the idea of drug delivery. By picking the right kind of materials for designing NPs, the release profile can be altered [38]. In addition, nanotechnology opens the way to alter the property of materials at the molecular scale, prompting the production of materials with different delivery rates that are, to a great degree, controllable [40]. Nanocarriers may offer a long dissemination time of medications inside the body, while bigger particles will, in general, be expelled a lot quicker than NPs. In other words, bigger particles will, in general, be accumulated in the spleen and liver instead of in target areas. Smaller particles tend to be taken up by different cells inside the body, including target cells [41].

Engineering plays an important role in the delivery of genes using nanomaterials, as conducted using gene guns. Gene guns have been demonstrated to be helpful in conveyance of DNA within the human body [42]. These conveyance devices are basically quickening agents of tiny carrier particles loaded with DNA for direct delivery into tissue-specific places, which ensures perfect transfection of DNA [43]. NPs or submicron particles are commonly required to infiltrate to a specific depth inside the target to complete the ideal impact of quality conveyance, and as such, the infiltration depth of these particles is one of the significant factors examined for the application of gene guns [44].

3. Challenges, Perspectives and Progress of NPs

The link between the formation and role of NPs is still to be explored. Commonly, NPs adsorb plasma proteins, which subsequently interact with the immune system of the body. Free radicals may be formed because of them, which can likewise cause genotoxicity. The cost of nanomedicines is very high compared to classical treatments due to the use of expensive characterisation instruments. In addition, nanomedicines show an updated stage of safety when contrasted with conventional treatments, yet medical care experts do not ordinarily suggest upgradation in the adequacy level. In general, nanomedicines have an interesting potential to diminish the dose frequency, enhance bioavailability in the light of the decreased size of particles and large surface area. In any case, the fundamental concern is how viable and safe are nanomedicines. Even if any definition makes the pharmacokinetic profile better, nanomedicines, however, produce toxicants inside the body, thus restricting their roles [45][46].

Nanomedicines generally play a significant role in compelling medication delivery. Medication targeting had become more conceivable because of these nanomaterials. Both passive and active targeting should be possible easily [47][48]. Likewise, the expanded surface features bring about proficient medication retention and thus can improve bioavailability. However, the two key difficulties related to them are the immune system response and cytotoxicity, which should be investigated fundamentally. Nanomaterial characterisation is another basic challenge, where various techniques like fluorescence-based tests and cytotoxicity tests are prevented because of the physicochemical properties of nanomaterials. It is suggested that the efficiency of medication loading be emphasised, along with decreasing the delivered doses. Furthermore, it is also recommended that smart nanomaterials that can skip the immune response and do not affect the surrounding environment of the diseased tissue be developed.

This entry is adapted from the peer-reviewed paper 10.3390/molecules26041077

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