Introduction:
Caseinova
Burns are one of medicine's oldest, deadliest, and most underestimated wounds.
Caseinova presents a novel approach to effective burn wound treatment.
The Problem:
Every year, over 10 million people suffer from burn injuries worldwide [1]. Despite advances in modern medicine, many wounds still heal poorly, often get infected, and leave both physical and psychological scars. Early and effective wound care is critical, but even with proper treatment, scarring and complications remain common.
The Global Impact:
Burn injuries represent a staggering yet underappreciated global health crisis, with 7 to 12 million people requiring medical attention for burns each year - that’s up to 33,000 cases every single day [2]. This burden falls especially hard on vulnerable populations: in low- and middle-income countries, limited access to medical infrastructure and early intervention makes burns significantly more life-threatening [3]. In India alone, over 1 million people suffer moderate to severe burns annually, and child mortality from burns in these regions is more than seven times higher than in wealthier nations [3].
The impacts of burn wounds are often lifelong. Survivors may face chronic pain, loss of skin function, disfigurement, and psychological trauma such as depression, post-traumatic stress disorder and even suicidal ideation - symptoms that can persist for years, even more than a decade after the initial injury [4, 5]. These outcomes frequently result in long-term disability and social isolation, especially where rehabilitation services are limited or unavailable.
Downfall of Antibiotic Treatement
Traditionally, antibiotics are used to ensure faster and complication-free healing of burn wounds, as the skin loses its protective barrier. However, the global rise in antimicrobial resistance has made burn wound infections increasingly difficult to treat [6].
Pseudomonas aeruginosa
Staphylococcus aureus
Acinetobacter baumannii
Pseudomonas aeruginosa, Staphylococcus aureus, and Acinetobacter baumannii are among the main bacterial pathogens responsible for burn wound infections - once easily treated, these now often lead to prolonged hospital stays, increased mortality rates, and pose a significant burden on healthcare systems [7].
As resistance grows, fewer antibiotics remain effective. Some bacterial strains have become resistant to nearly all available drugs, leaving very limited or no treatment options at all [8].
Without an effective solution, this global health burden will continue to claim thousands of lives annually and cause lifelong disabilities for countless more.
From Problem to Project:
Recognizing the severity and global impact of burn injuries, our team was inspired to search for a solution that could go beyond traditional wound care. Modern burn wound care is based on several standard treatments, yet each approach has different disadvantages that can negatively affect patient recovery. There are three major groups into which these treatments can be classified[9].
1. Silver-Based Creams
Historically, creams such as silver sulfadiazine and mafenide acetate have been widely used to reduce superficial bacterial colonization. However, clinical evidence suggests that silver-based products can potentially delay wound recovery, and if overused, they can contribute to antimicrobial resistance development[9].
2. Conventional Dressings
Conventional dressings such as silicone gel sheets or gauze are standard care options. However, these dressings often adhere to wounds, causing pain and tissue trauma during removal. They frequently fail to provide adequate moisture and protection from infection[10].
3. Biological Dressings
Advanced treatment options include biological dressings and skin grafting techniques. While they are sometimes effective for temporary wound coverage, they do not permanently replace the skin, face immune rejection risks, and have a limited supply. Hydrogel dressings can maintain a moist environment but alone lack the mechanical strength, targeted antibacterial action, or the ability to promote robust tissue regeneration and revascularization[11, 12].
In summary, there are many treatment methods to support burn wound healing, but each falls short in some aspect of providing optimal and uninterrupted recovery. We believed that by combining cutting-edge science with creative problem-solving, we could overcome these limitations and reimagine wound care for the people who need it the most.
Project Foundation:
Motivated by the urgent need for better solutions, our team set out to address this challenge by harnessing the potential of synthetic biology and a fresh perspective. In the early stages of ideation, we asked ourselves: What if we could create a smart wound healing material from naturally derived, accessible components? What if cells didn’t just survive burns - but were guided to rebuild?
These questions became the foundation of our project, leading us to explore innovative ways to support the body's natural healing process.
Ideal solution should:
- Maintain a moist environment to promote optimal healing;
- Absorb excess wound fluids to prevent tissue maceration;
- Provide a physical and biochemical barrier to prevent infection;
- Be non-adherent, requiring fewer dressing changes to minimise trauma;
- Be composed of biocompatible materials that support tissue regeneration.
Through our analysis, we identified several key criteria of an ideal burn wound treatment. While these criteria may seem numerous, each one plays a critical role in achieving safe, effective, and patient-centered healing.
Our goals:
Guided by this framework, we set out to design a solution that could meet all of these needs.
Our project goals emerged naturally from this analysis.
Develop a biocompatible wound-healing system from nature-derived materials.
Implement target bacterial action without relying on antibiotics.
Promote healing of severe burns and minimize pain,complications, and disabilty.
From vision to reality:
Design-Build-Test-Learn
During the development of our project, we actively engaged with experts across biomedical research, clinical burn care, and material science to validate our ideas and refine the solution design. These interdisciplinary consultations became an integral part of our design-build-test-learn cycle.
Clinical Experts Feedback
Early in the design phase, clinical experts raised concerns regarding the infection risks associated with protein-based materials such as casein. This valuable feedback prompted us to explore natural antibacterial additives, including propolis and bacteriophages.
Exploration:
Propolis (sometimes called “bee glue”)[14] is a bee-derived product that has been traditionally used as a wound healer and antiseptic component due to its antimicrobial properties. It consists of a mixture of components, mostly beeswax and plant-derived substances[15], with higher flavonoid levels linked to greater antimicrobial efficacy[16].
It has demonstrated efficacy against a wide range of bacteria (Gram-positive, Gram-negative, aerobic, anaerobic) and viruses[14]. It is particularly effective against Staphylococcus aureus[14], which often causes infections in burn wounds, especially antibiotic-resistant strains[17]. This useful compound can be electrospun[15, 16] into fibers suitable for incorporation into scaffold structures.
Another approach that has recently regained popularity as a promising alternative to extensive usage of antibiotics is phage therapy. Bacteriophages(also known as “phages”) are viruses that infect and use bacterial cells to replicate. They offer a highly specific and effective treatment, as they are host specific[18] and therefore cannot harm humans. Since they replicate within bacteria, repeated administration is often unnecessary. Phages can replicate by lytic or lysogenic cycles. In both cases, the phage attaches to its host bacteria to introduce its genome into the cytoplasm, utilizing bacterial ribosomes to produce its proteins[19].
Recent studies have explored phage incorporation into hydrogels, as hydrogels are ideal carriers for bacteriophages due to their biodegradability, biocompatibility and high water absorption effects[18]. The antimicrobial effect has been found to be comparable to that of antibiotic treatment[20], but without the associated risk of promoting antimicrobial resistance. Although the combined use of antibiotics and phages often yields the best results[18, 20], phages alone may suffice when the goal is infection prevention rather than treatment. By integrating targeted (phage-based) and broad-spectrum (propolis-based) antimicrobial mechanisms, our approach combines specificity and versatility to proactively prevent infection development in burn wounds.
As we transitioned to material design, input from material scientists guided our choices for the final product material composition leading us to select hyaluronic acid (HA) as a biocompatible component for the hydrogel with beneficial biological properties.
Simultaneously, discussions with clinicians emphasized the need to reduce dressing change frequency, hospitalization time, and systemic antibiotic usage. These insights ultimately guided the integration of our phage-based antimicrobial system. To address the concerns highlighted by medical professionals, we aimed to design a long-term dressing that lowers costs and hospital visits while improving patient well-being by reducing psychological burdens, since frequent dressing changes and hospital visits are not only costly but have also been linked to negative psychological outcomes, including heightened anxiety and depression[21,22].
Selected Model Phages:
To this end, we selected three well-characterized model phages for proof-of-concept experiments:
T4 (lytic), a widely studied phage with a prominent role in molecular biology discoveries[26].
Lambda, a popular model organism, notable for it s ability to switch between lysogenic and lytic cycles[27].
T7 (lytic), from the Podoviridae family commonly used as a model phage in microbiology.
By integrating targeted (phage-based) and broad-spectrum (propolis-based) antimicrobial mechanisms, our approach combines specificity and versatility to proactively prevent infection development in burn wounds.
Our solution:
To address the unmet challenges in burn care, we have been developing a biocompatible wound-healing system specifically tailored for burn injuries. Our design integrates structural support, targeted antimicrobial protection, and regenerative guidance - offering a comprehensive alternative to conventional treatments.
Structural Component: Electrospun Casein-Propolis Scaffold
At the core of our system is a nanofiber scaffold composed of recombinant casein blended with propolis. Through electrospinning these fibers are restructured to imitate type III collagen - the primary protein found in early wound healing. This structure mimics the extracellular matrix (ECM) and provides mechanical stability and a biologically active surface-area architecture that supports cell attachment, migration, and proliferation. Because electrospun casein is biocompatible and degradable, it can remain in situ, forming a scaffold that supports fibroblast and myofibroblast ingrowth. Over time, these cells replace the casein network with natural extracellular matrix components, such as collagen and glycoproteins[23,24]. Casein-based scaffolds have been shown to promote granulation tissue formation and modulate
inflammatory responses[25,26], while the inclusion of propolis enhances antimicrobial performance without compromising cell compatibility. This combination allows the scaffold to not only maintain wound integrity but also guide tissue regeneration - something passive dressings cannot achieve.
Protective Component: Bacteriophage-Loaded Hydrogel Coating
To complement the scaffold, we designed a surface layer of casein–hyaluronic acid hydrogel. Despite its simplicity, this layer fulfills essential functions: maintaining a moist wound environment, reducing dehydration, and physically inhibiting bacterial motility and metabolism, which supports epithelialization and reduces tissue dehydration - critical for optimal healing [30,31]. Crucially, it also acts as a delivery vehicle for bacteriophages, providing localized, targeted action against pathogens commonly found in burn infections, such as Staphylococcus aureus and Pseudomonas aeruginosa[32–35].
Phages offer several advantages over antibiotics: highly specific to their bacterial targets, self-replicating within infected areas, and do not disrupt healthy microbiota or contribute to the rise of antimicrobial resistance. Given the growing threat of antibiotic resistance and the need to minimize systemic drug exposure, integrating local antimicrobial mechanisms is a critical advancement. The resulting material design is not only biologically effective but also addresses comfort, autonomy, and quality of life - key priorities in patient-centered healthcare.
Through these collaborative efforts, we transformed our concept into a robust therapeutic material that is both scientifically grounded and clinically informed.
Why this approach matters:
This integrated dressing - combining regenerative support with targeted antimicrobial protection - addresses not only biological effectiveness but also patient comfort, autonomy, and quality of life. Beyond covering wounds, it engages the body’s healing mechanisms, overcoming limitations of current treatments and enabling large-area application. We see it as a next-generation platform with the potential to improve outcomes for millions of burn patients worldwide.
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