Researchers at Harvard University have developed a model of burn injuries that will allow them to investigate the mechanisms underlying healing in such injuries and test out new approaches to enhance this process. Burns can take a long time to heal and can be prone to infection and complicated by the presence of large quantities of dead tissue at the injury site. Modeling these processes in vitro will allow researchers to improve on the current standard of care for burn patients and avoid using experimental animals. The model includes a collagen hydrogel that is seeded with fibroblasts, supportive cells that normally help to build skin and other tissues. Burn injuries can be mimicked in the hydrogel construct using a cauterizing knife or a laser to create a burnt area to simulate the injury. The researchers have already used the model to discover that fibroblasts may not behave as expected in burn injuries.
Burns are a difficult experience for patients as they can prove challenging to heal, can be prone to bacterial infection, and are complicated by the presence of cauterized blood vessels and dead tissue. Burn injury healing has been classified into four phases by clinicians: bleeding stoppage, inflammation, new tissue formation, and tissue strengthening. Better understanding cell behavior during these phases will allow researchers to design better treatments. At present, it is thought that during the initial stages of healing that immune cells begin the job of clearing away dead tissue and killing any bacteria that are present.
“Depending on the injury, the extent and duration of these four phases can vary wildly across different wound types,” said Jeroen Eyckmans, a researcher involved in the study. “Given that laceration wounds are well perfused with blood, they tend to heal well. However, in burns, the blood vessels are cauterized, preventing blood from entering the wound bed and slowing down the healing process. Severe burn wounds also have large amounts of dead tissue that physically block new tissue formation.”
To investigate further, these researchers developed a collagen hydrogel base that they also seeded with fibroblasts and created ‘burn injuries’ using a microdissection knife or a high-energy laser. By observing cell behavior after the burns, the researchers have already discovered something surprising about the role of fibroblasts.
“During healing, we found that the fibroblasts first cleared the damaged material from the wound before depositing new material,” said Eyckmans. “This was a surprising finding because removal of dead tissue has been attributed to specialized immune cells such as macrophages, and fibroblasts have been considered to be tissue-building cells, not tissue-removal cells.”
Study in journal APL Bioengineering: Fibroblast clearance of damaged tissue following laser ablation in engineered microtissues