As we age, the fear of losing our youthful heads of hair crosses most of our minds. Although hair loss –– medically known as alopecia –– is common, it’s viewed as a bane by many, and the number of people seeking solutions is staggering. According to Grand View Research, Inc., the global alopecia market is expected to reach USD 14.2 billion by 2028.

Bacterial infections, immune reactions, stress, chemotherapy, hormonal imbalances, smoking, and poor nutrition are all potential hair-loss triggers. However, the most common type of alopecia, called androgenetic alopecia, is genetic, making it difficult to prevent its onset through diet and lifestyle-related measures alone.

To date, the U.S. Food and Drug Administration has approved only two alopecia medications: minoxidil and finasteride. However, patients must commit to lifelong usage, and serious side effects such as hypertrichosis, edema, and cardiovascular issues may arise. Hair transplantation, which involves moving hair from one part of the head to another, is costly and not guaranteed to be permanent. Patients also need to have a sufficient number of hair grafts in the first place, ruling it out as a treatment option for completely bald patients.      

As non-pharmaceutical solutions, shampoos, and oral supplements containing nutraceuticals such as biotin, keratin, vitamins (B, E, and D), plant extracts, and essential oils are widely available and are not associated with any significant adverse effects.

However, nutraceuticals are not subjected to the same rigorous testing as pharmaceuticals, so their ability to promote hair growth and thickness is not well established. Among branded nutraceuticals, Nutrafol and Viviscal, which are formulated with a concoction of plant extracts and are marketed as “100% drug free”, are popular and have demonstrated some efficacy in randomized, placebo-controlled trials.

How macromolecules can aid hair growth  

Ki Su Kim and Dong-Wook Han, research professors at Pusan National University, South Korea, believe that integrating biologically active macromolecules with pharmaceuticals is a highly promising strategy for treating alopecia.

“Recent research has focused on three main objectives: new drugs with improved efficacy and reduced side effects, targeted delivery methods for pharmaceutical products to the hair follicle, and transplanting tissue-engineered hair follicles,” said Han.

Biologically active macromolecules can help regenerate hair follicles by not only protecting the drugs they contain but also by facilitating scalp penetration, enhancing the transfer efficiency and thus the effectiveness of the treatment. Novel nanomaterial systems include lipid nanoparticles, polymeric nanoparticles, and extracellular vesicles.  

Microneedles composed of biodegradable polymers are also promising. They offer the dual benefit of painless scalp penetration and precise drug delivery, more accurately targeting the hair follicle than topical applications. Macromolecule-based microneedles are also flexible and can be fabricated as patches that enable controlled drug release.

“Tissue-engineering approaches, including hair-follicle engineering and artificial skin platforms, utilize macromolecules to promote hair-follicle development in laboratory settings and replicate the structure and interactions found in natural skin,” added Han. “Engineered hair follicles could be genetically modified to exhibit robust regenerative properties, and high success rates can be achieved when utilizing cells derived from the patient.”

Another promising non-pharmaceutical hair-loss treatment is low-level laser therapy (LLLT), a non-invasive therapy that uses near-infrared light to penetrate tissues and stimulate the transition of hair follicles from the resting phase to the growth phase.

The iHelmet is one commercially available LLLT device that can be used at home. Approved by the U.S. Food and Drug Administration, the model LTD200S is equipped with 200 laser diodes, and treatments are customized using a mobile phone app.

The efficacy of the iHelmet was recently evaluated in a real-world study involving 1383 participants, which concluded that the device was moderately effective for over half the users with mild or moderate-to-severe androgenetic alopecia and significantly effective for 20–28% of the users. The treatment efficacy of the iHelmet was improved when combined with drug treatment.

The integration of biologically active macromolecules with LLLT is an emerging strategy for accelerating wound healing and is expected to be applied to the regeneration of scalp hair follicles in the future.

The future of hair regeneration

Although these treatment methods may offer partial solutions, they do not address the underlying cause of androgenetic hair loss –– a hormone called dihydroxytestosterone (DHT). Inactivating the androgen receptor gene associated with DHT has the potential to revolutionize the treatment of androgenetic alopecia.

In the future, a gene-editing tools such as CRISPR-Cas9 would allow for targeted changes, including additions, deletions, and alterations, of the androgen receptor gene and other genes implicated in the onset of the condition, such as the SRD5A2 gene.

In CRISPR-Cas9, the Cas9 enzyme acts as “molecular scissors” to cut DNA at a specific location with the help of a guide RNA. However, for androgenic alopecia, precisely delivering Cas9 to the dermal papilla cells in the hair follicle is challenging using conventional protein-carrier systems.

To overcome this hurdle, researchers have developed a microbubble-based carrier system to deliver Cas9 complexed with single-carrier RNA to the hair follicle with the assistance of ultrasound. Topical application of the nanoparticle system was shown to stimulate hair growth in an animal model. These results, reported in 2020, are promising as an initial step toward normalizing the technology.   

“While gene-editing technology is not yet universally applicable for overcoming or preventing all diseases or disabilities in the clinic, it is expected to hold significant promise as a foundational method for addressing hair loss in the future,” said Han.

Reference: Moon Sung Kang, Ki Su Kim, Dong-Wook Han, et al., Recent Trends in Macromolecule-Based Approaches for Hair Loss Treatment, Macromolecular Bioscience (2023). DOI: 10.1002/mabi.202300148

Feature image credit: Darya Ogurtsova on Unsplash