Biomedical breakthroughs in self-healing materials

There is a class of materials that have the unique ability to recover from mechanical, thermal, and chemical-induced damage to restore their original properties without external assistance. Known as “self-healing” materials, these substances are a promising area of research in the biomedical field, where they have applications in wound care, medical devices, drug delivery, and more.

Only certain substances can self-heal while being compatible with human tissues and the complex conditions inside the body. Our latest research using the CAS Content Collection^TM reveals which materials have the greatest potential for these biomedical advances and which applications have made the greatest progress already.

How self-healing materials work

“Self-healing” can refer to many materials that can repair themselves on a macroscopic or molecular level after being damaged. In biomedical applications, the most commonly used self-healing materials incorporate polymers — i.e., large molecules bonded together — that are modified so that they can form reversible chemical bonds. A wide variety of polymers, including naturally derived materials such as chitosan and synthetic materials like PEG, are being actively researched in self-healing biomedical applications. Inorganic materials, coordination compounds, and metals are also well-represented in current literature (see Figure 1).

Polymers feature qualities such as flexibility and biocompatibility, which are important for use in the human body. They can also have side groups that can be engineered to participate in self-healing interactions in addition to their other properties. For example, self-healing materials often have hydrogen bonds in their chemical makeup, which are common in proteins and can be easily broken and re-formed even at room temperature.

What does that re-forming look like? Consider a gel-like substance being pushed through a needle. If the gel contains reversible, self-healing bonds, those bonds can be temporarily broken due to the stress on the gel as it passes through the needle, causing it to become liquid-like.

Those bonds can then re-form, restoring the gel-type properties of the substance in the body after injection.

Current and future medical applications

Self-healing materials are already used in many implanted devices, wound dressings, and drug delivery systems. Some of the most exciting research today involves hydrogels, a large umbrella of water-based, biocompatible materials that can be engineered to have self-healing properties. Soft contact lenses are an example of a hydrogel in biomedical usage, but researchers are finding even more potential uses for these materials:

• Wound care: Hydrogels can mimic human tissues with their softness and flexibility, and they can be engineered with antibacterial properties, all of which aid in wound healing. For example, a group of researchers developed a hydrogel that can be injected into irregular deep-burn wound beds. Others created an injectable, biocompatible self-healing hydrogel for wounds near body parts that undergo frequent stretching, such as knees and elbows.
  
  Notably, natural polymers like chitosan and cellulose are used in these hydrogels. These plant-derived materials offer good stability inside the body and are widely available. They can also be chemically modified to have self-healing properties, which explains why natural polymers are so frequently cited in publications on hydrogels (see Figure 2).

  

• Tissue scaffolding: Self-healing hydrogels are showing promise in regenerative medicine, particularly for promoting the development of tissues and organs. When acting as scaffolds, these materials can mend themselves inside the body even if they sustain an injury, thereby promoting tissue growth and repair.
  
  For example, researchers developed a mechanically compliant interpenetrating polymer network (IPN) hydrogel using polyacrylamide (PAAM) and gelatin. The PAAM/gelatin hydrogel matched natural vocal cord tissue in physical and chemical properties, so it functioned as an artificial adhesive tissue implant for voice repair.
  
  Researchers in China also developed a fiber-hydrogel composite scaffold for muscle generation. The fiber was electrospun from a mixture of graphene, melatonin, and a biocompatible polymer such as polylactic acid or polycaprolactone, while a hyaluronic acid derivative was used as the hydrogel matrix.
  
  Hydrogels can also be used for hard tissue regeneration, as one group of researchers demonstrated. The hydrogel composite contained calcium phosphate forming reversible bonds with polyacrylic acid-carboxymethyl chitosan-treated dentin matrix, followed by dynamic ionic and hydrogen bonds in the matrix. This study showed that the hydrogel retained its bioactivity and promoted the regeneration of dentin/bone hard tissue.

• Drug delivery: Hydrogels can be designed with reversible crosslinks that break when they experience shear strain going through a needle. The gel will flow like a liquid during injection and then can re-form into a gel inside the body. These materials can also be loaded with medications — in microcapsules, for example — that can be delivered to targeted locations.
  
  For instance, researchers showed that a pH-responsive injectable hydrogel can deliver cancer treatment drugs to specific sites in the body and then break down after delivery. Another team of researchers used a hydrogel to deliver chemotherapy, with the drug being activated using an ultrasonic horn after injection. Yet another hydrogel was injected into a tumor resection cavity to deliver electrotherapy targeting residual cancer cells post-surgery. The biphasic material allowed the electrode to conform to the cavity’s edges while generating low-voltage electric fields close to the tumor site.

Key materials to watch

Our analysis of documents and citations in the CAS Content Collection shows steady growth in journal publications on self-healing materials over the last 20 years. A recent increase in the journal-to-patent ratio suggests that the focus is still on early-stage development rather than commercialization.

Many chemical interactions can be used to impart self-healing properties to polymers, including covalent and non-covalent bonds. Examples of covalent interactions include dynamic Schiff base linkages, which are widely used for biomaterials and have grown significantly in the last five years. These linkages are based on reactions between a nucleophile and an aldehyde or ketone to form a bond, typically an imine or oxime, which is reversible in the presence of water. An example of this is a self-healing hydrogel based on a mixture of dialdehyde-modified hyaluronic acid and cystamine.

Hydrogen bonding, as mentioned previously, is a common non-covalent interaction, along with hydrophobic, host-guest, electrostatic, π-π stacking, and metal-ligand coordination interactions, notably those between catechols and iron(III) ions.

We’re also seeing a significant increase in the use of diisocyanates (see Figure 3), which are used in the synthesis of polyurethanes. This suggests that polyurethanes are an emerging class of substances in self-healing materials. Recent patent publications have discussed polyurethanes used in self-healing wound dressings and a heparin-functionalized polyurethane with self-healing properties based on hydrogen bonding and disulfide bonds.

Today’s research, tomorrow’s breakthroughs

Self-healing materials still have many hurdles to overcome before they’re widely commercialized for medical use. In many cases, they must undergo extensive clinical trials to ensure safety and efficacy. While these innovations are largely experimental, they hold immense potential for personalized medicine and improved quality of life for patients. They can speed up healing, prevent infections, deliver medications in hard-to-reach areas of the body, and improve the devices that assist bodily systems.

By leveraging nature’s best materials with chemistry innovations, the scientific community can open up new possibilities for health and recovery with self-healing materials. Learn more about self-healing materials and emerging trends in the rapidly evolving field of biomaterials in our latest Insight Report.

This article incorporates research completed in collaboration with Westlake University, China.