Recognition templates for biomaterials with engineered bioreactivity

摘要

Biology ubiquitously uses molecular recognition and specificity to do its work. In contrast, the biomaterials widely used in medicine today non-specifically adsorb complex protein mixtures to their surfaces. These ill-defined protein layers are "read" by the cells (neutrophils, macrophages) that interrogate the implanted materials - the protein coat may be the trigger of subsequent biological reactions. Given the heterogeneity in composition (there are 200+ proteins in blood) and organization (proteins are adsorbed with no control of orientation or conformation) of adsorbed protein layers, it is no surprise that biological reactions, particularly in vivo, are poorly controlled. If fact, implanted synthetic materials are almost universally seen by the body as foreign objects and walled off into a tough, avascular, collagenous bag1. Medical implants are widely used clinically and save lives and improve the quality of life for millions (Table 1). Medical implants are primarily fabricated from synthetic materials (polymers, metals, ceramics, glasses). These implants are walled off from the body within 3 weeks of implantation as described above. This implant encapsulation can impede the healing and performance of many devices. Capsule formation around implants may be a manifestation of the lack of recognition by the body of the nonspecifically adsorbed proteins coating the implant. In contrast to synthetic materials, biological tissue and normal wounds heal by a different process. Normal wound healing and integration are characterized by the absence of a collagenous capsule, new blood vessel formation and reconstruction of damaged tissues. Obviously, this normal reconstruction should be preferable to the aberrant, capsular healing noted with modern, "biocompatible" biomaterials. Is it possible to convert synthetic biomaterials to materials that will heal in the body by controlling the non-specific protein adsorption and thus use the surfaces of materials to deliver correct healing signals to the body? The approach of increasing the recognition and specificity of biomaterial surfaces is being pursued in our research group. With appropriate recognition structures on biomaterials, we may be able turn on normal healing rather having the biomaterial targeted as foreign.