In Situ Material Transformations in Tissue Engineering

Abstract

Novel applications exist for biomedical materials that can undergo transitions in material properties in situ—that is, at the site of implantation in the body. Such transitions in polymeric biomaterials can be accomplished by crosslinking a material in situ, by heating or cooling to induce thermal transitions, and by precipitating polymer from solution in situ. This article will point out the need for materials that can be induced to undergo such transitions in situ and will describe selected tissue-engineering approaches that have been employed for this purpose.Delivering materials to the body in one form and utilizing them in another form after a transition at the site of implantation has, generally speaking, two potential advantages: (1) the ability to match the morphology of a material implant to a complex tissue shape and (2) the ability to deliver a large device through a small hole in the body. With respect to the former motivation, tissue shapes in the body have an enormous range of complexity: a region of a blood vessel—for example with a curved central axis, a diameter that varies along the length, an eccentric diseased plaque, and numerous side branches. One could develop a variety of implant shapes—arterial stents in this example (for use in structurally supporting arteries after balloon angioplasty, thereby creating a larger cross section for blood flow above the diseased plaque)—and then select the most appropriate implant shape after detailed imaging of the tissue site. One can alternatively attempt to employ some material transformation to deliver a precursor to the final shape of the implant, utilizing the tissue shape to obtain the proper final implant morphology. With regard to the second motivation, it may be desirable to deliver a large object through a small hole, utilizing material transformations. Advances in surgery have focused on manipulating (cutting, coagulating, suturing, stapling) large tissue sites through small holes in the body via minimally invasive surgery. Using such approaches, it has become possible to perform many complex surgical procedures in the joints, abdominopelvic cavity, thoracic cavity, and nasal sinuses, for example, using surgical instruments that are manipulated through surgical access holes less than 1 cm in diameter. Even procedures as complex as coronary-artery bypass surgery have been performed in this way. It still remains generally impossible however to implant devices in the body through such holes unless these implants are very small. If such devices were for example able to be delivered as liquids and then shaped into devices at the implant site, such minimally invasive surgical-device placement could be envisioned.