Despite centuries of medical insight and advancement, predicting how a patient will heal after surgery remains challenging. Factors such as age, lifestyle, genetics, comorbidities, and unforeseen complications all influence the healing process. Some patients recover quickly with minimal scarring, while others experience delayed healing, excessive inflammation, or complications like infection and fibrosis. A deeper understanding of the molecular mechanisms that regulate healing and inflammation is essential for improving patient outcomes. Biomarker analysis offers a powerful tool to decode these processes, enabling healthcare professionals to anticipate complications and adjust treatment plans to accelerate and enhance healing.

“Designing products that optimize the right mix of biomarkers at different stages of healing and regeneration enhances treatment options and supports personalized medical interventions,” said Greg Mouchka, President of iFyber, a preclinical contract research organization specializing in custom research and development services. “As our knowledge of biomarkers continues to expand and grow, and the barriers to measuring them drop, we can incorporate biomarker analysis into many aspects of patient care.”

How Biomarker Analysis Can Improve Surgical Outcomes

Medical advancements are bringing real-time cytokine monitoring closer to reality. These emerging technologies have the potential to revolutionize patient care by enabling faster and more precise insights into the healing process.

• Point-of-care testing will make it possible to measure cytokine levels in real time without relying on a central lab. Currently, some hospitals and research settings use portable and handheld immunoassay devices to measure inflammatory markers; however, they are not yet widely used in routine clinical practice.
• Liquid biopsy techniques use blood or other bodily fluids to detect biomarkers related to inflammation and healing. These procedures are already used to detect cancer biomarkers and infectious diseases, but cytokine-based liquid biopsy tests for real-time surgical site monitoring are still in development.
• Wearable biosensors will be a non-invasive way to track cytokine fluctuations and immune responses in real time continuously. While still in the research phase, early prototypes show promise for monitoring inflammation and immune activity with precision.

The potential benefits of real-time cytokine monitoring are substantial and include:

• Early detection of complications. Persistently high levels of cytokines like IL-6 and TNF-α may indicate an unresolved infection or ongoing inflammation, while low levels of the growth factor VEGF can signal impaired angiogenesis, leading to poor blood supply and ischemic wound complications.
• Personalized interventions. By analyzing cytokine and growth factor levels, clinicians may one day tailor post-surgical interventions to an individual’s healing response. For example, patients with elevated levels of the growth factor TGF-β are at risk of fibrosis and may benefit from antifibrotic therapies to reduce excessive scarring.
• Optimized postoperative management. Real-time cytokine monitoring can help clinicians evaluate the effectiveness of post-surgical care and make data-driven adjustments. This could include modifying antibiotic regimens, selecting appropriate wound dressings, or adjusting rehabilitation protocols based on a patient’s unique healing profile.

The Role of Cytokines in Monitoring Surgical Site Healing

Cytokines and growth factors are essential to every phase of surgical site healing, directly influencing tissue recovery. Below are key cytokines and growth factors involved in this process, along with the potential benefits of monitoring their activity.

Interleukin-6 (IL-6) and Tumor Necrosis Factor-Alpha (TNF-α)

IL-6 is an early responder in wound healing. It helps activate immune cells and stimulate the acute inflammatory response. TNF-α is another pro-inflammatory cytokine that helps recruit white blood cells to an injury site. Both IL-6 and TNF-α are necessary for the early inflammatory phase of healing, but their levels must decline at the right time to allow for new tissue to form. Persistent inflammation, marked by elevated IL-6 and TNF-α, may indicate an underlying issue such as infection, impaired healing, or even the early stages of chronic wounds. Monitoring these cytokines could help clinicians identify complications and intervene with antimicrobial treatments or anti-inflammatory therapies.

Vascular Endothelial Growth Factor (VEGF)

VEGF plays a key role in angiogenesis by stimulating endothelial cell growth. Insufficient VEGF can result in poor blood supply and slow healing, while too much may lead to abnormal vessel growth and fibrosis. Tracking VEGF levels in surgical wounds could help identify patients at risk for delayed healing and prevent excessive scarring.

Epidermal Growth Factor (EGF)

EGF plays a critical role in wound healing by helping skin cells move across the wound to close it. When EGF levels are too low, this process slows down, leading to delayed wound closure and an increased risk of infection. Chronic wounds, such as diabetic ulcers or pressure sores, often show reduced EGF activity. By monitoring EGF levels, clinicians can identify patients at risk for slow healing and explore targeted interventions, such as topical growth factor therapies or advanced wound care strategies.

Transforming Growth Factor-Beta (TGF-β)

TGF-β helps control fibroblast activity and collagen production, making it essential for tissue repair. High TGF-β levels can indicate a greater likelihood of hypertrophic scarring, keloids, or even internal fibrosis. Tracking TGF-β levels can help predict fibrosis risk and prevent excessive scarring or complications like hypertrophic scars and keloids.

Matrix Metalloproteinases (MMPs) and Their Inhibitors (TIMPs)

MMPs and TIMPs work together to heal wounds. MMPs help break down damaged tissue and clear the way for new cell growth, while TIMPs keep MMP activity in check to prevent excessive tissue degradation. This is a delicate balance. When MMP levels are too high, they can break down healthy tissue along with damaged tissue, prolonging the inflammatory phase and preventing wound closure. This is often seen in chronic wounds, such as diabetic ulcers. If TIMPs suppress MMP activity too much, the extracellular matrix isn’t broken down and rebuilt properly, leading to collagen buildup and fibrosis. Monitoring MMP and TIMP levels can help clinicians identify complications like chronic inflammation, poor tissue regeneration, and excessive scarring.

“The advancements in biomarker monitoring are both promising and astonishing. For example, iFyber has run projects developing in vitro diagnostics for biomarkers of various types. Our group also measures how biomarkers are showing up in samples taken during clinical trials. Additionally, we can use models of healing, both in vitro and in vivo, to evaluate medical device prototypes that show how they influence the cytokine profile of a healing site,” said Mouchka.

“However, there are challenges the healthcare community needs to overcome before these tools can become standard clinical practice. There needs to be a perfect balance of science marrying up with clinical needs and economic factors, like the cost of production and insurance companies buy-in, before widespread testing becomes available.”

Partner with iFyber for Biomarker Analysis Support

Leveraging biomarker analysis will allow clinicians to personalize interventions, improve surgical outcomes, and optimize patient recovery, and iFyber has the scientific expertise to support your team. Our diverse team of scientists and engineers have a deep understanding and years of experience in the research and development of wound care devices. For biomarker analysis, we work with clients to develop assays for various biomarkers and sample types, with particular emphasis on the wound care field.

To explore biomarker analysis and other analytical services, or to learn how you can partner with iFyber to bring your innovations to live, contact us today.