Nanotechnology's Role In Future Wound Care

Nanotechnology in wound care

What is nanotechnology?

Nanotechnology is a branch of science that combines many different scientific disciplines,, from biology and chemistry to physics and engineering, to address areas of unmet clinical needs. It focuses on the synthesis and applications of materials that measure on a nanometre scale in at least one dimension, making them incredibly small.¹ For context, a nanometer is one billionth of a metre! 

These materials can be used in a variety of different ways, from medical applications in wound care to the production of quantum dots used in semiconductors. Because these materials are so small, scientists largely focus on their properties when in large quantities, studying how they interact with other materials to ensure their safety in potential medical treatments.

Wound healing and nanotechnology

The materials synthesised in the area of nanotechnology are unique in many ways. Due to their incredibly small size, nanoparticles are able to interact with a target within the body on a molecular level. This is an advantage that can be harnessed to create new or improved methods of treatment within the field of wound care management. 

Advances in the field of nanotechnologies may improve the treatment time required for wound healing or even provide new options for treating chronic wounds (wounds that have not progressed through all the stages of wound healing within the normal time frame or wounds that will not heal due to various internal/external factors).²

Currently, nanomaterials are being utilised for the accelerated healing of severe burns and gashes via a topical hydrogel applied to the skin. Hydrogel as a wound dressing is showing promise in holding and diffusing antibacterial drugs at the wound site, alongside human biocompatibility by infusion with the nanoparticle Chitosan to reduce immune response. Carbon-based nanoparticles, such as carbon nanotubes and diamond-like carbon, are used in wound healing to reduce the adhesion of bacteria to the site of injury and promote stem cell and growth factor development for faster, uninterrupted healing.   

Understanding wound healing and its challenges

Phases of wound healing

There are four main stages of wound healing: hemostasis, inflammation, proliferation, and tissue remodelling.² These stages can overlap but should still happen in order for successful wound healing to occur. The usual time frame for wound healing is around four to six weeks.

1. Hemostasis is the first process the body uses to stop bleeding at the site of a wound. This involves constriction of the blood vessels (vasoconstriction) and the aggregation of platelets at the site of the wound to stop the flow of blood and form a clot, respectively.³
2. Inflammation is the second stage of wound healing and involves white blood cells and platelet cells (thrombocytes). Platelet-derived growth factors attract fibroblasts to promote the synthesis of collagen, and white blood cells (monocytes and macrophages) are involved in the ‘cleaning up’ of the wound site by removing cell debris via phagocytosis.³
3. Proliferation is the third stage of wound healing, but it also occurs in the background of the other stages. It involves re-epithelialization (the reformation of the epithelial layer of cells that make up your skin, destroyed by injury). Initially, this is only a single thin layer of cells, but subsequently, more cells will bridge over this to create a thicker, more durable layer. 

Angiogenesis also occurs in the proliferative phase, whereby new blood vessels are formed to replace those that were damaged or destroyed by injury to the tissue; these are essential for oxygenation (delivery of oxygen) of the wound site. 

Wound healing is further supported by the initial deposition of collagen fibres to strengthen the tissue as the wound begins to mature and contract.³

4. Tissue remodelling is the final stage of wound healing, and it starts around week 3 of the process. The remodelling phase primarily involves the degradation of excess collagen deposition, giving rise to increased skin cell and myofibroblast populations, resulting in strong and durable tissue. 

Myofibroblasts are cells that contribute to the overall scaffold-like matrix of the tissue and, like muscle cells, are able to contract to promote wound closure.⁸  Whilst wound healing is robust, the resulting scar tissue will only recover around 80% of the surrounding tissue’s tensile strength.³

What affects wound healing?  

The appropriate healing of a wound should follow the steps outlined in ‘Phases of wound healing’. Delay or complete inability to progress through the natural stages of wound healing can cause impairment in wound repair and an increase in inflammatory processes as the body struggles to heal and fight infection simultaneously. Dehiscence (the splitting open of a closing or closed wound) is often caused by infection of the injury before the healing process is complete and can interfere with appropriate wound healing. 

Additional factors that interfere with wound healing include (but are not limited to):

• A lack of oxygen supply to the surrounding tissue infection 
• Disease (diabetes mellitus)
• Medications (including corticosteroids and anti-inflammatory drugs(NSAIDS)) 
• Age
• Stress 

Some issues, like infection, are caused by poor wound treatment at the time of injury (improper cleaning of the wound) or later in the treatment process (improper dressing of the wound and/or failing to use the correct type of dressing). Whilst there are well-established solutions to these factors (such as adequate training and education on sterile wound care);  other issues, such as underlying disease and age, are factors that require a more comprehensive response. Herein lies a role for nanotechnology in wound care.

A role for nanotechnology in wound healing

Different nanoparticles have different physical properties, and not all of them can be applied to wound care treatments with similar success. For example, it has been shown that metallic nanoparticles from inorganic substances, such as silver and gold, are much more effective than organic nanoparticles in wound treatment. This is largely owed to their smaller molecular size, lower tissue toxicity and higher rates of reactivity in boosting the wound healing process.⁹

Enhanced antibacterial capabilities

Silver has been used in wound treatment for its antibacterial properties for hundreds of years but is not without its limitations - toxicity, skin discolouration, and bacterial resistance. 

Despite this, it has been employed extensively in a wide array of medical approaches ranging from surgery to topical creams and wound care. 

Effective at very low concentrations,⁴ silver nanoparticles are very useful in preventing infection at small doses. This is particularly advantageous, as they can be used to bypass the negative effects associated with the use of larger quantities of silver particles, such as toxicity following the first few days to weeks of healing and loss of effectiveness on clean wounds, by increasing the surface area to volume ratio of the material within the tissue. In turn, this exploits its natural antimicrobial properties at the wound site.  

Acceleration of tissue regeneration

Nanoparticles may also be used to accelerate the wound healing process as some nanoparticles, including silver, display anti-inflammatory properties.⁴ 

The use of anti-inflammatory nanoparticles may help to speed up the healing process by reducing the amount of white blood cells released by the body’s immune system in response to the detection of any foreign material at the wound site. This accelerated regeneration of tissue may also contribute to reduced scarring once the wound has healed.

Controlled drug delivery for pain management and healing

Because nanoparticles are so small, they can be used to directly target areas of infection and they can also deliver drugs directly to the target site. This ‘local delivery’ reduces unwanted side effects caused by some drugs when they are delivered systemically (i.e. via the circulatory system), and increases their availability at the wound. 

Often, side effects are caused by a drug’s ‘off-target’ actions within the surrounding tissue and other organs. Essentially, nanoparticles are excellent in preventing this, allowing for specific and targeted drug delivery at precise dosages. This ensures that other cells in the surrounding tissue (and body) remain unaffected by the drug’s actions. 

Future applications of nanotechnology in wound care

Smart bandages with sensing capabilities

Smart bandages appear to be incredibly useful in solving the limitations of traditional bandages for different types of wounds. For example, a bandage that can monitor the development of an infection at the wound site would be particularly useful in allowing prompt treatment of the infection before the condition worsens or results in a chronic wound. 

One possibility is to utilise an indicator that changes the colour of the bandage so it is visible when a wound becomes infected. Methylene blue, a dye that fades from blue to white in the presence of infection-causing bacteria, is one such example.⁵ 

These smart bandages can also be combined with nanoparticles to include other beneficial properties, such as the antibacterial properties of silver.

Nanofibers and scaffolds for tissue engineering

In some cases, a wound may be too significant to heal without the aid of a tissue graft, either from the patient or a donor. Here, nanofibers may be extremely useful in speeding up the tissue regeneration process. 

Often, problems associated with the use of tissue grafts, such as limited availability or an immune response resulting in graft rejection, are difficult to overcome. In response to this issue, tissue engineering (a multidisciplinary field involving biology, chemistry, and engineering) has developed an approach that isolates healthy cells from an individual and deposits them onto a biodegradable scaffold that can be integrated into the wound. Importantly, these cells can interact with growth factors placed within the scaffold to create new tissue, and while the scaffold degrades over time, it is replaced with newly formed tissue. 

Nanofibers can be used to create the scaffold due to their favourable properties, such as microporous structure, which allows better cell adhesion.⁶ The most commonly used polymers for nanofiber scaffolds are organic in nature, to allow degradation within the tissue. Examples are collagen, keratin, and cellulose.

Benefits and advantages

From the examples we have discussed here, it is clear that nanoparticles are incredibly useful in many ways and have the potential to revolutionise wound care treatment. 

Their primary advantages centred around the material's natural antibacterial properties, employed to prevent infection and the subsequent development of chronic wounds. The innovative generation of smart bandages can facilitate monitoring of wound infection by the patient at home, allowing the patient to seek medical care promptly when required.

The benefits of this technology are both time- and cost-saving for the patient and healthcare provider, ultimately improving healing time and quality of life for the patient.

Challenges and ethical considerations

In medical applications, there are some concerns with the use of nanoparticles that have yet to be fully explored. For example, if metal-based nanoparticles are ingested or enter the respiratory or vascular system, they have the potential to cause cytotoxicity (toxicity to cells) in the liver, lungs, vasculature, and other organs.

In the vasculature, nanoparticles might activate coagulation factors, induce endothelial cell damage, and promote inflammation to increase the risk of blood clots.¹⁰  Currently, it’s unclear if metal-based nanoparticles used in bandages can enter the body through a wound and accumulate systemically to form a blood clot. Importantly,  blood clots can lead to serious complications such as heart attack, stroke, pulmonary embolism and deep vein thrombosis. 

Future challenges in nanoparticle technology will seek to provide a better understanding of the safety of exposure to nanoparticles in medical applications for both the patient and healthcare professional. Another important consideration is the environmental impact of nanoparticles. This concerns the production and disposal of inorganic, metal-based nanoparticles used in wound care. To better understand this, studies are beginning to address the potentially damaging impact of nanotechnology on wildlife, ocean life and agricultural ecosystems.¹¹ 

Future trends and possibilities

In the setting of wound care, there is currently some interest in the use of graphene oxide;a highly-oxidised form of graphene, resulting in a sheet of carbon only a single atom thick. Researchers are exploring graphene oxide and its potential applications as a scaffold material for tissue engineering.⁷ 

A major problem at the moment with nanotechnology is its difficulties relating to cost and availability; at present, there is a large bottleneck in the production pipeline where many nanomaterials made from precious metals, such as gold and silver, are costly to produce and integrate. Future works may explore improving its accessibility for general use in wound care. 

Conclusion

Nanotechnology involves the use of incredibly small materials (on a nanometre scale) that have a variety of properties that make it an excellent therapeutic tool in the setting of wound treatment. Metal-based nanotechnologies are anti-bacterial, accelerate tissue regeneration and can provide targeted drug delivery, making them particularly useful in wound-care management.