Bone
An electromagnetic property may be intrinsic in the structure of biological materials, where it plays a specific functional role. This was observed as a result of the search for a simple, easily isolatable growth system with well-defined input and output parameters. Healing processes as previously described are complex, involving major cellular reactions and a variety of biochemical changes within the entire organism. Morphogenetic growth in the embryo is even more complex, involving, in addition, interactions between structures as they form and genetically preprogrammed factors.
There is however, a growth phenomenon, unique to bone, that is ideal for such an analysis. In 1892., Wolff systematized the growth response of living bone to mechanical stress into a specific law that subsequently has become known as "Wolff's Law." Simply stated, bone grows in response to mechanical stress so as to produce an anatomical structure best able to resist the applied stress. For example, should a fracture of a weight-bearing long bone heal with an angulation, each step that the patient subsequently took would result in a bending stress with compression on the concave side at the angulation and tension on the convex side. Rather than progressively weaken the bone structure at this site, such repeated mechanical stress results in a "remodeling," with new bone growth on the concave side and bone resorption on the convex side. If the patient is young enough, the bone will ultimately through this process grow straight. In control system terms, the applied mechanical stress causes a growth response that negates the applied stress; a closed-loop negative-feedback control system. Such systems imply the presence of transducers producing a signal proportional to the stress and indicating its direction. The system may be schematicized as:
In the simplest analysis, some component of the bone itself may be considered to have the property of transduction inherent in its structure. It is now known that the structure of bone is that of a complex, biphasic material with an organizational complexity extending down to the molecular level. The basic phase is the collagen fibril, a long-chain fibrous protein produced by the bone cells (osteocytes) and deposited in a highly organized pattern that determines the gross structure of each bone. The second phase is a microcrystalline, inorganic mineral, hydroxyapatite, that is deposited in a very precise fashion directly on the pre-existing collagen fibers. Both materials, in their correct relationship at the molecular level, are necessary to produce bone with its unique mechanical properties. By using appropriate chemical extraction treatment, either phase can be removed leaving the other intact; that is, a "bone" of collagen alone or one of apatite alone. Each lacks the normal characteristics of whole bone; the collagen alone being soft and flexible, and the apatite alone being hard and very brittle, yet each looks very much like an intact whole bone. In life, the intact bone is composed mainly of this biphasic material, which is actually non-living. The only living portion of the bone is the population of the bone cells, the osteocytes, which constitutes approximately 10% of the total mass.
In certain inorganic crystalline materials having a nonsymmetrical lattice, the application of mechanical stress results in the displacement of charges within the lattice that can be sensed as a pulse of electricity on the exterior surface of the crystal. With release of the mechanical stress, a pulse equal in magnitude but opposite in polarity is produced. This property is called piezoelectricity, and in 1954 it occurred to a Japanese orthopedic surgeon, Iwao Yasuda, that bone might be piezoelectric, with the mechanically produced electrical signals being the stimulus that produced bone growth according to Wolff's law. He was able to actually demonstrate piezoelectricity in whole bone that year (50) and in the following year he stimulated the growth of bone in experimental animals by the application of electrical currents. Later, in conjunction with another Japanese scientist, Eiichi Fukada, he was able to show that the piezoelectric property also existed in the collagen fibers of tendon (51). Subsequently, this same property has been found in the collagen fibers of many different tissues.
In 1962, Bassett and Becker extended these observations using fresh whole bone subjected to bending stress (52). They noted under these conditions that the signal produced by the application of stress was greater in magnitude than the opposite polarity signal produced by the release of the stress, leading to the postulate that some rectification of the one signal was occurring in the bone matrix.
In a search for the source of this possible rectification we studied the properties of each matrix component separately and together in their normal configuration. We found that both collagen and apatite had some properties similar to semiconductivity, with collagen appearing to be an "N" type material and apatite a "P" type. The junction between the two in whole bone was then found to have some electrical and photoelectric properties similar to those of a rectifying PN junction (53, 54). In this view, the piezoelectric property of collagen generated the electrical signals upon the application and release of mechanical stress, with the signal of one polarity rectified to some extent by the PN junction of the collagen-apatite relationship. In bending stress therefore, the concave side of the bone demonstrates an overall negative polarity under stress, while the convex side is primarily positive in polarity. Since bone growth occurs according to Wolff's law on the concave side and bone resorption on the convex side, negative potentials were postulated to produce stimulation of the osteoblasts and osteocytes, while positive potentials were presumed to either facilitate bone resorption by stimulating specific cells that destroy bone (osteoclasts) or merely not to produce any stimulation of bone growth on the convex side. In a test of this hypothesis, Bassett, Pawluk and Becker were able to demonstrate that bone growth did occur in the vicinity of a negative electrode with currents of less than 3 µamp, while growth was absent around the corresponding anode (55). It should be noted that the currents were not strictly analogous to those produced by the piezoelectric effect in whole bone, being continuous rather than intermittent as would occur in normal usage.
The control system schematic for the growth of bone in response to bending stress may be expanded as follows:
Later we explored the apatite-collagen junction in whole bone with quite different techniques. With trace element analysis techniques, Spadaro, Becker, and Bachman demonstrated that the bone collagen fibril possessed a surface site capable of absorbing specific metallic cations depending upon the radius of the hydrated ion (56). Elements with radii between 0.65-0.75 A and between 1.2-1.4 A were bound tightly to the fiber. The copper ion in its cupric state (CuII) with a radius of 0.65 A was found to bind to both collagen and apatite. We later utilized this property to explore the electronic state of the binding site using electron paramagnetic resonance (EPR) techniques. This ion normally has a simple EPR signal, but when bound to either collagen or apatite, it demonstrated a complex resonance spectrum with the resonances in each case being identical, indicating that the binding sites on both apatite and collagen were identical in electronic configuration (57). This is of course a rather unique situation considering the great difference between these two materials, one being fibrous protein and the other an inorganic mineral crystal. We proposed that this structural similarity of the two materials could be involved in the initial mineralization process (the deposition of the first apatite crystals directly on the fibers) (58).
The situation in response to a compressional stress may be somewhat less complicated, as we later determined. In this case, as stress is applied and released, the electrical pulses measured on the surface of the bone were similar to those measured on a simple piezoelectric crystal under the same circumstance-oscillation between a positive or a negative value and a zero baseline without a polarity reversal. Yet applying the same concept of bone growth with a negative polarity and resorption with a positive polarity, the predicted growth pattern in response to the compressional stress was very similar to that actually observed (59). In this case there is no need to invoke a rectification property, with the orientation of the collagen fibers inherent in the normal structure of the long bone presumably being sufficient to produce the necessary polarities (60).
In either event, bone may well be considered to be the first actual identified representative of the theoretical "self-organizing systems." If one begins with a pre-existing bone structure whose pattern is determined by genetic factors, provides a supply of collagen as soluble fibrils and an aqueous environment with inorganic ion constituents capable of nucleating hydroxyapatite, then the application of mechanical stress to the preexisting matrix will produce the deposition of new bone matrix in the areas of compression, with collagen fibers oriented to best resist the applied stress. Of course in the living system, the osteocytes and osteoblasts are stimulated by the negative electrical environment to produce the additional collagen molecules, which then orient in the electrical field and subsequently nucleate hydroxyapatite crystals from the inorganic components of the tissue fluids.