Biomimetic model systems for investigating the amorphous precursor pathway and its role in biomineralization.

Biologically-formed hard tissues, referred to as biominerals, have intrigued the materials engineering community for years because of the high degree of crystallographic control that is exerted during the precipitation of the bioinorganic crystals. In recent years, there has been a shift in attention, from prior studies that focused on specific organic-inorganic interactions that modulate the crystal morphology via the conventional crystallization pathway, to recent studies that find that many biominerals are formed via an amorphous precursor pathway. It has become clear that the things we thought we had learned about biominerals before, may or may not be relevant to truly understanding the mechanisms involved in biomineralization. Having witnessed this paradigm shift first hand, I am inclined to provide a review from this historical perspective, where I hope to belay some ideas about where we were, where we are, and where we are going, with respect to understanding how these shells and other biominerals are formed. Therefore, one goal of this review is to try and provide a link between the prior literature and the new literature, which might be useful to newcomers in the field, whom I suspect may find it confusing and difficult to integrate the findings in these different types of studies across this time period. A second goal is to try and integrate some of the knowledge obtained from in vitro model systems, which can be more amenable to obtaining mechanistic information, with the in vivo and ex vivo observational studies on biominerals. A third goal is to demonstrate that there may be certain unifying principles found in biomineral systems that seem widely diverse, such as from diatoms, to mollusk shells, to vertebrate bones and teeth. A final goal (the not so hidden agenda), is to demonstrate that not only is there as strong likelihood that many biominerals are formed by an amorphous precursor, but that the amorphous phase may possess fluidic properties that impart new processing capabilities to the system. Of course those who know my work will readily assess that I am referring to the polymer-induced liquid-precursor (PILP) process, which has been a primary focus in my lab. Along these lines, some new hypotheses are presented regarding the morphogenesis of certain biominerals, such as mollusk nacre, kidney stones, and bones and teeth, along with a review of the literature that provides support to these new ideas. The intent is to stimulate thoughtful discussions in this rapidly emerging area, which seemingly provides a unifying principle in biomineralization. 1.1. Biomineral Overview Biominerals that have intrigued the materials engineer for years. The diversity of biominerals became particularly evident by the variety of books on biominerals that emerged in the late 80’s to 90’s,1–11 which has continued with a few more recent additions to this nice collection.12–16 Many people are probably not even aware of the diversity of biologically formed minerals, so a sampling is provided in Table 1 to illustrate some of the different chemistries that evolved in the formation of various biological hard tissues. The calcium carbonate (CaCO3) biominerals of invertebrates, such as mollusk shells and sea urchin spines, have been particularly well studied due to their accessibility, and because of the high degree of crystallographic control that is achieved in these biologically formed crystals. The calcium phosphate (CaP) biominerals of the vertebrates, such as bones and teeth, have also been extensively investigated because of their remarkable structure and mechanical properties, and for the more obvious reasons of health related issues.14 Calcium oxalate (CaOx) biominerals can be found in plants, but the majority of studies have focused on the pathological form of CaOx that is found in kidney stones, which often occurs in conjunction with CaP deposits.8,14 Table 1 Examples of the diversity of biominerals. This list is by no means comprehensive, where some 70 different mineral phases have been identified to date.1–11