Bioglass

Preface
There are thousands of materials available to mankind based on four primary classifications of materials: metals, ceramics, polymers and mixtures of each called composite. From these materials we build structures, vehicles, apparel. Everything we see and touch is made from materials, both natural and man-made. There are millions of designs possible to suit millions of mechanical, electrical, structural and aesthetic needs. Biological needs are different and are more demanding. The living body is protected by an immune system that efficiently and systematically rejects any unnatural material it considers foreign. With this limitation, materials for biological purposes are severely limited and the options are significantly reduced. Of the copious amounts of materials available, less than 50 can coexist within the body. Metallic hip implants, ceramic [\coasted electrodes] and polymeric sutures are a few examples of acceptable biomaterials that do not illicit an unfavorable immunological response. All of these materials either dwell or degrade in the body having no bonding with living tissue.

Bioglass is the first synthetic material that bonds with living tissue. Many new and exciting properties have been discovered making it a candidate for an entirely new class of regenerative materials, those able to restore function of damaged or diseased tissues.

__Snapshot of Bioglass Properties__
 * Bioactive
 * Bonds to bone and soft tissue
 * Osteoproductive
 * Bioresorbable
 * Antimicrobial
 * Proangiogenic

History
Bioglass was discovered in 1969 by Dr. Larry Hench at the University of Materials Science and Engineering. The biomaterials field at that time was nacient and flooded with trial-an-error based materials that exhibited bioinert responses at best. That is, implanted materials were not detrimental to the body. Instead, metals, polymers required a mechanical fit in the implanted area. Bioglass revolutionized the biomaterials field when it was discovered that the original 45S5 composition bonded directly to bone tissue. 45S5 has been the leading representative of bioactive materials for over 40 years.

Instead of an inert firbrous capsule, Bioglass materials develop a bone-like, apatite film on the bioactive surface upon contact with physiological fluids. The low-silica glass undergoes partial dissolution and surface reorganization through a 5 step process which releases key ions that have been found to stimulate bone growth. The apatite layer is sufficiently passivated to prevent high dissolution rates, allowing a stable interfacial layer that enables migration of collage, and other biomolecules to the interface where osteoclastic activity begins. Bioglass is highly biocompatible and stable with appreciable rates of bonding.

Clinical applications include replacement of defects such as i.e. middle-ear, maxiofacial, periodontal. This limitation to non-loading applications is due in principle to the low strength and toughness of bioceramics.

Melts-Derived BG
The first BG product was the MRI. It was cast BG used to replace the osicciular bone of the middle ear (see Bioceramics 2nd Ed.) The second BG product was the EMRI. These were cones of BG implanted in the endoseous ridge to support periodontal implants.

These forms of BIoglass stemmed from research conducted by June Wilson who discovered that BG bonded not only to hard tissue, but also soft tissue.

From Melts to Particles
The critical concentrations of Ca and P serve to stimulate the production of bone. This discovery of osteostimulation and osteoproduction of BG proceded from work by June Wilson. Key ions for stimulation of osteoblasts are released from BG substrate. The efficiency magnified with particulate forms of BG. [\evidence for enhanced bone tissue development of Class A bioactive materials]
 * BG particles in 6mm defect grew new bone in rabbit by 1 week
 * Small particles (<90 um) resorbed over long periods
 * Larger particles (200-300 um) were incorporated in the tissue matrix, suggesting bone bridging between particles, unlike HA particles
 * Faster resorption rates for 58S and 77S bioactive gel-glass

Osteostimulation of BG particles led to applications of bone stimulation and bony defect filling. The third BG product was developed. known as Perioglass, which is sold worldwide with millions of sale each year.



The particulate form applied to the repair of periodontal defects and periodontal disease is perhaps the most widely important clinical application of Bioglass. Bioglass granules have been used to fill bony defects pioneered by Wilson. Bone tissue has been found to grow around the particles following subsequent resorption over time. This discovery of new bone growth positioned Bioglass as an osteoproductive material, enable the initiation and proliferation of bone tissue on Bioglass surfaces and throughout a void space. This enhanced osteoclastic activity categoriezes Biolglass as Class A bioactive material. Class B materials are osteostimulate, such as synthetic hydroxapatite, which are able to maintain a stable interface with bone, but have limited osteoclastic activity at the surface or away from the implant. [\i.Insert bioactivity kinetics diagram L. L. Hench, J. Am. Ceram. Soc., 1998, 81, 1705.]

The discovery of tubule occlusion for the reduction of tooth sensitivity and antibacterial has led to the development of Perioglass (TM), a toothpaste contain Bioglass particles, which has aided millions of patients in oral care. It was discovered that the balance of alkalinity in Perioglass aided maintaining healthy teeth [d.Hench lecture info].

Research with particulate Bioglass led to further discoveries of its ability to bond not only to bone tissue but also to soft tissue as well, including muscles and ligaments. More recent research has led to discoveries of Bioglass having regenerative properties that reproduce new bone tissue, replicating the structural and mechanical integrity of host tissue. Regenerative medicine is the latest stage of Bioglass research in the field of tissue engineering.

From Particles to Scaffolds
Work by Hench, Julian Jones, Boccacinni, Polak, Xynos and others led to discoveries that BG controlled genetics cell cycles through the upregulation and expression of 7 gene families. Some of the genetic processes involve the triggering apoptosis of damaged or diseased cells, and the proliferation of healthy cells during mitosis of osteoblasts. This work supports the idea of the regenerative properties of BG to differentiation and proliferate cells. [\Genetic Control of BG Particles]

Porous forms of BG were developed of use as bone scaffolds. The production of Bioglass-dervice scaffolds is a topic of recent interest in the field of tissue engineering. Scaffold provide a 3D porous network that can restore bony defects while supporting the vasculature necessary for maintaining healthy new bone over longer distances in vivo. In addition, stem cells can be seeded withing the scaffolds to initiate the production of new tissue. Bioglass scaffods have been developed with promising new discoveries related to the dissolution release of key ions that initiate osteoproduction. At first it was hypothesized that the release of sodium, calcium and silica ions were necessary for high bioactivity [\r.] The discoveries of osteoproduction with Ca-Si Bioglass scaffolds refined the understanding that a critical Ca/Si concentration is required. ]

[\Table of historical properties discovered from BG and its forms]
 * ~ __BG Forms__ ||~ __Properties__ ||
 * ~ Melts || * Bonds to living tissue ||
 * ~ Particles || * Promotes bone growth
 * Bioresorbs ||
 * ~ Scaffolds || * Porous network for osteoinegration
 * Genetic control of cell cycles; osteostimulation ||

From Macroscopic to Nanoscopic
[\Reserach has extended to the nanoscopic aspects of Bioglass] [\r.]

Computer simulations have led the charge for understanding the interaction of bioglass surfaces in aqueous environments. Modern computer modeling of bioactive glasses focused on the intial 5 step dissolution process. The necessary modeling power is is an atomic resolution of 0.1nm with ≤ ~10 μs. Therefore, the primary interest for modeling of bioglass involves (i) partial dissolution of bioactive surface and (ii) reactivity of surface. Bioactive glasses are modified to disrupt the silica network to allow dissolution into “chunks” or chains of Si-O-S. Lack of long range order heightens complexity of of the computational approach. A combined approach of using MD (for empirical potentials and initial glass structure information) and ab initio modeling (for first principles) has aided, for example, in understanding the influence of a range of phosphate concentrations on bioactivity. In MD, shell-model (SM) where polarizable atoms are replaced with core-shell dipoles. The MD trajectory is concerned with thermodynamic properties and dynamical process, which adopt empirical force fields. The ab initio approach uses first principles at short times (~40ps) with few atoms (100-300). The combined AIMD starts with a MD structure (with initial empirical potentials) followed by AI quantum modeling. Computer modeling seeks to analyze the number of of bonding oxygens (BO), the network connectivity (NC) or distribution of network-forming Si atom Qn, where Qn measured indirectly by NMR. In general, higher values of BO, NC or Qn lower bioactivity.

[\RELATIONSHIP OF MODELING TO FRACTALS]


 * Bioactive Glasses [and compositions]**
 * Bioglass 45S5
 * Bioactive gel-glasses