The global coronavirus disease 2019 (COVID-19) pandemic rages on. To date, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has infected over 138.3 million and caused over 2.9 million deaths the world over. Despite major gains in the global vaccination campaign, researchers are still searching for possible therapeutic options to mitigate disease severity in those it reaches. One area has been exploring the potential of biomaterials.
Biomaterials science is currently pushing the boundaries of emerging technologies for research and treatment. Biomaterials are effective platforms for drug delivery that can be used to develop antivirals. A few examples of biomaterials are hydrogels, cryogels, and nanoparticles (NPs, such as liposomes).
In a recent review, published in the journal Emergent Materials, a team of researchers gives their take on how biomaterials can be harnessed for therapeutic strategies against COVID-19.
Biomaterials are derived from natural or synthetic materials that have been engineered to interact with biological systems for therapeutic or diagnostic purposes.”
The team discussed how biomaterials can be used to design accurate and advanced COVID-19 infection models, enhance antiviral drug delivery, foster new antiviral strategies, and reinforce vaccine efficacy. A detailed look into these possibilities is essential for when more SARS-CoV-2 variants emerge that can resistant or evade current strategies of containment.
Although repurposing of available antiviral drugs has been employed to target SARS-CoV-2 due to the urgent need presented by the pandemic, the results have had mixed success.
This highlights the crucial need for the design of more accurate drug screening models, new drug delivery platforms, and innovative antiviral strategies. The reviewers point out that during this pandemic crisis, biomaterials have played a key role in the development of life-saving solutions in response to viral diseases (engineered bioprinting models and 3D in vitro tissue models), spanning from virus-deactivating surface coatings to treatment strategies and vaccines.
Drug screening models
The reviewers highlighted the lack of physiologically relevant in vitro models to understand both the host immune response against SARS-CoV-2. Vero cells, the current gold standard model for antiviral therapeutic screening, lack type I interferon gene clusters.
Interferon signaling is the first line of defense against viral infections and is also an important regulator of angiotensin-converting enzyme 2 (ACE2)— the receptor involved in SARS-CoV-2’s host cell infiltration. This explains the success of antiviral drugs in Vero cells, with little or no benefit to COVID-19 patients in clinics.
However, biomaterials engineered as biologically and chemically defined scaffolds or organoids can be used to model SARS-CoV-2 infection by recapitulating the complexity and spatial heterogeneity of the human body systems at a macroscale level. Organ-on-chip technologies could also be leveraged in this direction.
Drug delivery systems
The reviewers also discuss how biomaterials can be effective drug delivery systems: biomaterial-based delivery systems reduce drug dose and stabilize the antivirals, also provide better tissue targeting, alleviate systemic exposure, and limit off-target adverse effects. Because the properties of biomaterials (physicochemical characteristics, stimuli responsiveness, size, and geometry) are tunable, they can be adjusted to enhance biocompatibility and biostability, as well as to control and target drug delivery.
Biomaterials also exhibit high flexibility in terms of their mode of administration; oral administration, surgical implantation, injection, or inhalation can be considered.
Cellular nanovesicles use biomaterial-centered strategies, such as cell-mimicking NPs, to act as nanodecoys to trap and sequester the SARS-CoV-2 virus or as nanosponges to absorb and neutralize proinflammatory cytokines to alleviate cytokine storms in patients with severe COVID-19. The reviewers cited various examples where biomaterial-engineered nanovesicles perform functions against SARS-CoV-2, increasing high neutralizing activity, enhancing cytokine actions, or fabricate to act as models expressing ACE2.
For a safe and effective vaccine against SARS-CoV-2, which is also economical for large-scale production, several approaches can be explored. These include traditional vaccines based on inactivated or live virus, virus-vectored and subunit vaccines, and radically new technologies for vaccination using RNA or DNA. The reviewers have summarized the SARS-CoV-2 vaccine candidates that are currently in phase 3 clinical trials.
Moderna’s mRNA-1273 and Pfizer/BioNTech’s BNT162b2 mRNA vaccines are reportedly over 90% effective in preventing COVID-19; these rely on lipid NPs for enhanced intracellular delivery. This highlights the pivotal role of biomaterials in achieving high vaccine efficacy, possibly culminating in the end of the pandemic.
However, these vaccines pose several limitations: short-life, a requirement of cold storage, no minimal dose, and low immunogenicity. To overcome these shortcomings, scientists are employing different biomaterials to address each of these. For example, a SARS-CoV-2 mRNA vaccine encapsulated within liposomes composed of 2-distearoyl-sn-glycero-3-phosphocholine, cholesterol, and PEG, is stable for over 1 week at room temperature and triggers immunity against SARS-CoV-2.
Our lab has recently engineered oxygen-generating cryogels (O2-cryogels), a sophisticated and advanced macroporous hydrogel system, with the unique ability to reverse hypoxia-driven immunosuppression in solid tumors.”
The researchers have highlighted that the state-of-the-art biomaterials have the potential to serve as formidable tools in the fight against SARS-CoV-2. These efforts could not only contribute to stop or mitigate the current pandemic, but will also provide unorthodox platforms to understand, prevent, and protect us from future viral outbreaks, suggest the researchers.