Research

Biomaterials in tissue regeneration

Guided tissue regeneration is an emerging field, based on the notion that some biomaterials can induce ordered tissue regeneration by modulating the innate immune system.  Polysaccharide biomaterials are particularly attractive for this purpose. Some polysaccharides, such as hyaluronic acid, are present endogenously and others can be purified or derived from abundant natural sources.  Chitosan is a naturally-derived polymer that is created from chitin, a major structural component of shrimp shells. The polymer is composed of linear chains of N-acetyl glucosamine and glucosamine sugars.  The chitosan N-acetyl glucosamine content is known to influence neutrophil behavior and the glucosamine content, as we recently discovered, has a unique influence on macrophage behavior. In healthy individuals, immune cells called neutrophils and macrophages patrol the blood stream and tissues for infection and tissue damage. Macrophages will automatically engulf or "phagocytose" micro-organisms, dead cell debris, and microparticles of chitosan. The phagosome then matures into an acidic, hydrolytic vesicle that can destroy pathogens without harming the cell. Our laboratory recently discovered that chitosan microparticles have an interesting biomimetic property when their structure contains a cationic "patch" (15 or more consecutive glucosamines). Chitosans containing this cationic patch imitate the way that some pathogens have evolved to evade immune surveillance. The mechanism is triggered when chitosan particles escape from the uptake vesicle into the cytosol. At early stages of escape, the macrophage responds by releasing anti-inflammatory factors. We are using these findings to design biomaterials that promote bone and cartilage repair by modulating macrophage behavior. 

Blood clots

The blood clot is the first tissue to form in a surgical site. The blood clot is an under-studied tissue in regenerative medicine.  Our laboratory takes a molecules-to-tissues approach to guided tissue regeneration, by studying the molecular and cellular responses of whole blood to different types of biomaterials. Tissue engineering at the level of the blood clot can be used to guide the first steps of wound regeneration in a surgically treated wound.  Blood coagulation is a type of innate immune response that in ancient organisms was used to immobilize invading pathogens at the site of entry. Tissue engineering blood clots is a unique way of improving outcomes using one-time treatments administered at the point-of-care.

Innate immunity

The innate immune system is the first-line defense against infection and foreign body invasion. Innate immunity functions through an inter-connected system of tissue barriers (skin, epithelium), body fluids (tears, saliva, synovial fluid), blood factors (complement, coagulation factors, antimicrobial peptides) and cells (platelets, neutrophils, macrophages, dendritic cells). After hemostasis and blood clot formation, inflammation is the next step in wound repair. This response involves the release of soluble mediators that draw innate immune cells, blood vessels, and stem cells to a wound.  Polymers can be used to guide the inflammatory response in a way that favors angiogenesis and stem cell migration, while limiting tissue destruction. 

Bone and Cartilage

Bone is a mineralized mechanical tissue that allows us to move around. Our bones are also centers in our body that produce blood cells and mesenchymal stem cells.  When bone becomes fractured, it tends to heal spontaneously after surgical stabilization however research is on-going to determine how to boost repair in individuals with pre-existing conditions that inhibit repair.  Low-grade infections significantly delay fracture repair and research is on-going into how to determine whether delayed fracture repair is due to surgical site infection (SSI) or to fibrosis in the fracture site. Articular cartilage is a thin layer of elastic tissue that covers the ends of long bones. This tissue is important for maintaining a smooth and painless gliding movement when we walk. Regeneration of cartilage is very challenging because cartilage cells are trapped in a dense matrix and unable to proliferate and fill a lesion.  Microfracture is a surgical method to repair cartilage that involves creation of controlled damage to the subchondral bone, in order to allow mesenchymal stem cells from the bone marrow to migrate to the lesion and form a cartilage repair tissue.  Our laboratory has been at the forefront of research to understand how biomaterials can be used to induce bone and cartilage regeneration. A combination of approaches from in vitro, ex vivo, in vivo, and clinical sample testing is used to develop new therapeutic approaches. Our lab is also researching ways to using biomaterials to control synovial inflammation and produce higher quality repair cartilage.