Pulmonary fibrosis (PF) is a chronic interstitial lung disease that causes inflammation and scarring around the alveoli of the lung. The scarring is called fibrosis, where a patient experiences difficulty in breathing. This scarring around the tiny air sacs or alveoli causes the tissue in the lungs to get stiff, and the process of absorption of oxygen in the bloodstream becomes difficult. The progression of PF varies; some people experience a slow decline, whereas others can have periods of stability and then sudden worsening.(p1)

Idiopathic pulmonary fibrosis (IPF) is a term used when the cause behind the occurrence of this disease is not known. It is a long-term and growing fibrotic lung disease in which the normal or healthy lung tissues have an extracellular matrix (ECM) deposited on them, and the alveolar microstructure gets destroyed, which results in decreased oxygen absorption.(p2) Although a definite etiology of the disease is not known, some common causes are environmental exposure to different pollutants, occupational exposure to contaminants such as aluminum dust, asbestos dust, beryllium dust, coal mine dust, silica dust, textile dust, certain genetic factors and aging. A few medications, such as chemotherapeutic drugs (bleomycin), cardiac drugs (amiodarone and dronedarone) and antibiotics, and some medical conditions, such as autoimmune disorders, including rheumatoid arthritis, lupus and scleroderma, as well as smoking, could be responsible for PF.(p3)

PF is a very intricate disease, and its complexity is shared in its epidemiology. Diverse cohort studies are ongoing to understand its epidemiology.(p4) From the studies performed all over the globe, the prevalence of IPF, a sub-type of PF, was found to be greater within the population. Jo et al. concluded that the occurrence of IPF increases with age, and the average age of IPF patients is 65–70 years.(p5) From the studies, it was also found that the occurrence of the disease is higher in males than in females.(p6)

The current treatment options for PF include medications such as nintedanib and pirfenidone and the surgical option of a lung transplant. Nintedanib is a tyrosine kinase inhibitor approved for the treatment of IPF in the USA in 2014 and in Europe in 2015.(p7),(p8) Pirfenidone is a synthetic pyridine compound administered orally to treat IPF in adults. It was approved for use in Japan initially in 2008, then in Europe in 2011, and later in the USA in 2014.(p7),(p9) However, these conventional therapies for PF have many limitations in terms of their bioavailability, requiring relatively high doses with the related side effects.(p2) Although nintedanib and pirfenidone mitigate the rate of lung function decline, the disease tends to worsen over the period and often leads to end-stage respiratory failure, secondary pulmonary hypertension and ultimately death. When all the medical options for treating PF are exhausted, a lung transplant remains the only option, which could improve the survival and therefore life expectancy of the patients. However, lung transplant is associated with comorbidities and many disease-specific challenges, which restricts its use.(p10) At present, the overall market of drugs for PF was valued at US$3.78 billion in 2023 and is expected to grow to US$6.45 billion by 2031 at a compound annual growth rate (CAGR) of 6.9%.(p11) Therefore, there is a need for innovative therapies that can cure PF. Considering these challenges and limitations, scientists shifted research focus to the development of biotechnology-based treatment options such as monoclonal antibodies, nucleic acid delivery and stem cell therapy, which have the potential not just to eliminate the limitations faced by conventional therapies but also to overcome them. This review is focused on biotechnology-based treatment options for treating PF, including their advantages and limitations.