摘要REVISITING THE TERM"SMART BIOMATERIALS"Biomaterials have been employed to augment body functions and/or replace damaged tissues for the past several thousand years.1–2 Specifically, biomaterials have been instrumental in transforming medicine over the last few decades. Historically, there are three distinct generations of biomaterials which can be labeled as"bioinert","biocompatible"and"bioactive", depend-ing on the degree of their interactions with the body.3 The term"Smart Biomaterials"was first coined in 2004,4 describing materials"that respond to specific cellular signals". However, the exponential growth in the last decades of new biomaterials with clever, precise, and highly controlled biofunctionalities warrants a redefinition and clarification of the term. The term"smart"is relative to a particular point in time. Biomaterials that are currently considered"smart"could be considered"dumb"40 years from now. It is a safe bet to assume that today's"smart biomaterials"will be"outsmarted"by future innovations. There-fore, in this review, we propose a new classification for smart biomaterials according to their degree (or level) of interaction with their environment and the ensuing biological responses. This classification helps to clarify how smart a biomaterial is. This classification also recognizes the evolution of the concept"smartness"without cementing the definition of what a smart biomaterial is. Hence, it is appropriate to define a level or degree of smartness to help distinguish the materials' ability to elaborate different sets of biofunctionalities. Thus, defining a scale or degree of smartness will help clarify potential misconceptions, especially for novel biomaterials able to respond to different sources of stimuli. Utilizing control theory as inspiration,5 we propose to recognize four levels of smartness for biomaterials, namely inert, active, responsive, and autono-mous (Fig. 1). Such classification discerns the various classes of biomaterials according to their degree of interaction with the (bio)environment and, specifically, with biological/cellular processes.
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