**Doped Bioactive Glass Materials in Bone Regeneration**

Samit Kumar Nandi, Arnab Mahato, Biswanath Kundu and Prasenjit Mukherjee

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/63266

#### **Abstract**

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274 Advanced Techniques in Bone Regeneration

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In the arena of orthopaedic surgery, autograft is considered to be the gold standard for correction of fracture repair or other bone pathologies. But, it has some limitations such as donor site morbidity and shortage of supply, which evolved the use of allograft that also has some disadvantages such as immunogenic response to the host, low osteoge‐ nicity as well as possibilities of disease transmission. Despite the benefits of auto‐ grafts and allografts, the limitations of each have necessitated the pursuit of alternatives biomaterials that has the ability to initiate osteogenesis, and the graft should closely mimic the natural bone along with regeneration of fibroblasts. A variety of artificial materials such as demineralised bone matrix, coralline hydroxyapatite and calcium phosphate-based ceramics such as hydroxyapatite (HA), β-tricalcium phosphate (β-TCP) and bioactive glass have been used over the decades to fill bone defects almost without associated soft tissue development. Most of them were having only the properties of osteointegration and osteoconduction. Only bioactive glass possesses osteogenic property that stimulates proliferation and differentiation of osteoprogeni‐ tor cells and in some cases influencing the fibroblastic properties. But, this material has also some disadvantages such as short-term and low mechanical strength along with decreased fracture resistance; but, this was further minimised by ion doping that positively enhanced new bone formation. There are many metal ions such as magne‐ sium (Mg), strontium (Sr), manganese (Mn), iron (Fe), zinc (Zn), silver (Ag) and some rare earths that have been doped successfully into bioactive glass to enhance their mechanical and biological properties. In some of the cases, mesoporous bioactive glass materials with or without such doping have also been employed (with homogeneous distribution of pores in the size ranging between 2 and 50 nm). These biomaterials can be served as scaffold for bone regeneration with adequate mechanical properties to restore bone defects and facilitate healing process by regeneration of soft tissues as well. This chapter encompasses the use of bioactive glass in bulk and mesoporous form with doped therapeutic ions, their role in bone tissue regeneration, use as delivery of growth factors as well as coating material for orthopaedic implants.

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

### **1. Introduction**

Bone tissue repair and regeneration have made considerable strides in the modern era. An indepth perceptive of the underlying principles has been achieved, new methods and materials developed and a multidisciplinary approach was used to accomplish successful bone tissue regeneration. Many scaffold systems have been planned for hard tissue engineering. Novelty has been worked out in terms of scaffold design, material selection, inclusion of drugs and growth factors, mechanical stability and bone regeneration competence. Nevertheless, autografts are still considered as 'gold standard' for bone tissue repair; equivalent osteogenic or osteoinductive performance is not obtained by the synthetic bone graft substitutes. Due to limitations of autografts in sufficient quantities to meet the overall medical demand for orthopaedic implants, allografts and xenografts are alternatives sources to overcome such problems, but are having the risks of disease transmission and immune rejection. As a result, synthetic bone graft substitutes are the rational choice to meet the huge demand for orthopae‐ dic implants, even though its inherent limitations in terms of strength, osteoconduction, osteoinduction, osseointegration and biodegradation. Accordingly, modern research area has been focussed on development of new biomaterials, modification of mechanical and structur‐ alfeatures,improvementofbiocompatibility,osteoinductivityandtoincorporategrowthfactors and stem cells onto scaffolds to encourage bone regeneration.

Bone tissue regeneration strategies intend to use synthetic temporary templates to assist the natural healing of bone defects. Bone extracellular matrix (ECM) containing collagen fibrous structure, with mineralised calcium phosphate, is secreted from osteoblasts [1, 2]. For effective bone regeneration in non-load-bearing defects require a biomaterial scaffold that might have a three-dimensional (3D) fibrous structure mimicking the ECM [3–5] and can be easily placed into position during surgery. The scaffolds are also required to be biocompatible (should not elicit an inflammatory response nor exhibit immunogenicity or cytotoxicity), bioactive (bond with bone), bioresorbable, allow new bone formation at an acceptable rate, be economical to make and allow easy fabrication into the final preforms [6–8]. The scaffolds must be easily sterilisable to prevent infection especially for bulk degradable scaffolds [9]. Additionally, the mechanical properties of the scaffold must be optimal to prevent structural failure during handling and patient's normal activities. Furthermore, controllable interconnected porosity is of paramount necessity for cells to grow into the scaffold and to support angiogenesis. The scaffolds should also have porosity of 90% with pore diameter of at least 100 μm for proper cell penetration and vascularisation of the ingrown tissue [10–12].

A number of inorganic and organic materials are being used as bone substitutes that include calcium phosphate ceramics, phosphates of magnesium, sulphate, carbonate and silicate of calcium and collagen with positive cell-material interactions. Inert inorganic materials, such as alumina, zirconia, titanium alloy and cobalt-chromium alloy, are also used in hard tissue applications, but lack resorbability and absence of osseointegration at the bone-implant interface. Positive interaction with cells was established using synthetic biodegradable polymers, such as polylactic-co-glycolic acid (PLGA), polycaprolactone (PCL) and polyethy‐ lene glycol (PEG) [13, 14]. The degradation products of these materials have no detrimental effects in body system. Furthermore, degradation rate, hydrophilicity and mechanical strength can be controlled by changing the chemical composition. Many natural biopolymers are also available and are very suitable bone substitutes in terms of cell-material interactions. Large polymers of very high molecular weight such as chitosan, alginate, cellulose, gelatin, collagen, keratin and hyaluronic acid also exhibit favourable cell-material interactions. Additional biocompatibility to a structurally stable scaffold is the selection criteria for bone substitute materials currently in vogue [15, 16].

In bone tissue engineering, commonly used materials are ceramic and glass due to their superior biocompatibility. Poor mechanical strength and stability are the major deficits rendering them unsuitable as porous scaffolds. In addition, processing defects such as irregularly shaped pores, surface defects and residual stress, all reduce the mechanical strength of the scaffold systems. These limitations compelled the researchers to find out the solutions for the improvement of biological performance of these materials by combinations of various strategies to augment cell-material interactions and stimulation of cells to ensure rapid but controlled bone regeneration. One of the alternate strategies is metallic ion doping for improving biological performance enhancement.

The aim of this chapter is to summarise the recent advancement of metallic ion dopants in addition to bioactive glass scaffold and their studies in orthopaedic surgical challenges. Our discussion broadly covers innovations in materials development and fine tuning together with structural and functional improvisations.
