Technology success or technology failure?

Vascular substitutes (vascular grafts) are used today for hemodialysis blood access, wound repair, and cardiovascular reconstruction. The first synthetic vascular grafts (vascular substitutes) were developed after World War II and were made from materials such as parachute cloth and sewn on a home sewing machine. By the 1970s, commercial vascular grafts were available, mostly made of polyester fabric or expanded polytetrafluoroethylene (ePTFE).

These larger diameter (>5mm) grafts can satisfactorily replace or repair large vessels. However, there are many needs where a Small Diameter Vascular Graft (SDVG) will be beneficial. For example, there are approximately 1 million leg amputations worldwide, most of them due to blocked blood vessels.

Small-sized synthetic vascular grafts fail most often in this demanding, low-flow anatomical site. Also, surgeons would be happy to have a synthetic graft for heart bypass surgery, but SDVG won’t work in that area. The FDA has never approved a vascular graft smaller than 5 mm in diameter. Why haven’t the performance of vascular grafts improved after more than 70 years? Nearly 50,000 technical papers have been published on vascular grafts, many of which propose novel designs and novel biomaterials. Therefore, research is still ongoing, but there is no unified theory to drive the development of SDVG.

In an opinion article published in the journal BME frontier, formulate a new hypothesis that can reveal the path to the desired SDVG. After reviewing historical precedents and the advantages and disadvantages of many vascular grafting methods, the article proposes that we must mimic the structure and behavior of natural arteries.

Key elements of next-generation SDVGs will be a living, functional endothelial cell lining, a vascular network within the graft wall (“pseudo-vasa”) and a biomechanical match to the elasticity of the native artery being replaced. Importantly, the graft did not trigger a foreign body reaction (FBR), which can result in a fibrotic scar capsule with low vascularity and macrophage activation.

Most of the biomaterials we accept today (e.g. PTFE, Dacron) trigger this FBR. FBR reactions, if mild, are accepted by medical device regulators. However, it turns out that FBR is actually a manifestation of chronic inflammation—a constant, never-ending assault on biological material.

Biomaterials basically never really heal in the body. So the so-called biocompatible biomaterials might not be all that biocompatible! This ongoing inflammation inhibits the formation of a healthy layer of endothelial cells, while the rigid foreign body capsule prevents the normal curved pulsation of implanted grafts. Grafts exhibiting FBR are about to fail because they do not have a healthy, viable endothelial lining, and their non-curved walls and capsular contractures reduce blood flow and create flow impairments that lead to thrombosis.

Fortunately, new biomaterials are being developed to inhibit FBR and demonstrate reconstructive, regenerative healing. The paper’s central hypothesis suggests that these types of new materials could lead to successful vascular grafts that more closely mimic the properties of native arteries. A number of vascular graft approaches based on engineered native tissue have shown such regenerative healing and are being explored in the laboratory and in the clinic.

These are promising, but there are concerns about long-term durability due to the body’s mechanism for digesting old tissue. In addition, there are new biomaterials, such as porous structures with 40-micron interconnected pores, that can heal in a non-fibrotic, vascularized manner. These new vascular grafting methods offer the possibility that SDVGs heal in a reconstructive manner, functioning very much like the natural blood vessels they are intended to replace.

Provided by BMEF (BME Frontiers)