Periodontal Bone Substitutes Application Techniques and Cost Evaluation

© 2016 Jamaluddin Syed, Najmus Sahar, Raffaella Aversa, Relly Victoria V. Petrescu, Davide Apicella, Erum Khan, Michele Simeone, Florian Ion T. Petrescu and Antonio Apicella. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


The earliest bioactive materials which were used within the body were identified as called Prostheses (Hench and Thompson,Periodontal Bone Substitutes Application Techniques and Cost Evaluation Articles 2010). These Prostheses had to be standardized according to the physical properties of living tissues. Professor Bill Bonfield et al. (1981) was the pioneer of researching mechanical properties of living tissues, its skills were especially centered on bone to make Prosthesis. The basic objective of making the Prosthesis was to achieve a combination of physical properties of living tissue with minimal toxic response to the surrounding structures (Hench and Thompson, 2010). These prosthesis had the limitation of stress shielding and bone resorption. Professor Bill Bonfeild explore the concept of Bioactive materials and design bio composite that matches more to the mechanical properties of living tissues and removed the limitation i.e., resorption of the underlying bone structure (Hench and Thompson, 2010). The Bio active mechanism is the procedure through which living tissues are attached and integrated to an artificial implant with a chemical bond (Tilocca, 2009).

There are many applications of bioactive materials in tissue engineering (Tilocca, 2009). Tissue engineering is the art and science of biological substitution through which tissue function is restored. This is achieved with the formation of biological scaffold provide structural support to the tissue which later filled with number of cells and implantations (Chen et al., 2012). The requirements of scaffold materials to fulfill the demand of tissue engineering, are biocompatibility, the material doses not respond on unresolved inflammatory reaction, mechanical properties must be sufficient to prevent surface failure, controllable interconnected porosity which can help to grow cells and support vascularization (Chen et al., 2012). About 90% porosity with 100micrometer is essential for cell growth and proper vascularization (Chen et al., 2012). Bone has natural combination of inorganic calcium phosphatase appetite and a biological polymer called Collagen in which associates are deposited (Chen et al., 2012; Buzea et al., 2015).

In tissue engineering 3-dimensional scaffold is formed which is fabricated with natural or artificial materials exhibit high porosity and pore interconnectivity (Hoppe et al., 2011; Maeno et al., 2005; Sachot et al., 2013). The function of scaffold is not only to provide structural support to the bony structure but also to enhance cell proliferation and differentiation of Osteoblastic cell (Hoppe et al., 2011; Aversa et al., 2016). Several Inorganic Bioactive materials could form a desired porous scaffold with suitable mechanical properties. According to the researched literature the ionic dissolution is the key procedure through which inorganic material behavior in forming scaffold and interact with living tissue can be understood in vitro and Vivo. Some inorganic elements such as Sr, Cu, Co, Zn was already present in the human body and play anabolic effect on bone metabolism (Hoppe et al., 2011). The introduction of therapeutic ions in the scaffold material to increase its bioactivity (Sachot et al., 2013). The release of ions after exposure of physiological environments is effected on the bioactivity of scaffold related to osteogenisis and angiogenesis (Hench and Wilson, 1993; Hoppe et al., 2011; Hutmacher, 2000; Okuda et al., 2007).

Role of Inorganic Ions in Bone Metabolism

Human bone has natural process of healing through the process of remodeling. Remodeling is the process of deposition and resorption of bone tissue by Osteoblastic and Osteoclastic cell activities. As remodeling occurs, Osteoblastic cells produced new bone cells and Osteoclastic bone cells destroyed or resorbed existing bone. This formation and resorption process called Remodeling. Failure in maintaining the balance of remodeling results in multiple problems like Osteoporosis and Arthritis (Habib et al., 2007).

The remodeling procedure is regulated by few growth factors, hormones and inorganic ions such as Calcium (Ca) (Heinemann et al., 2013; Julien et al., 2007; Liu, 2003; Saltman and Strause, 1993), Phosphorous(p) (Heinemann et al., 2013; Julien et al., 2007), Silicon (Si) (Liu, 2003), Strontium(Sr) (Liu, 2003), Zinc(Zn) (Liu, 2003; Saltman and Strause, 1993), Boron(B), Vanadium(V), Cobalt (Co), Magnesium(Mg) (Cepelak et al., 2013), Magneese (Mn, Copper(Cu) (Liu, 2003; Saltman and Strause, 1993). Inorganic ions dissolution plays a very important role in the process of bone healing (Mouriño et al., 2012; Mirsayar et al., 2016, 2017; Petrescu et al., 2015, 2016 a-e; Petrescu and Calautit, 2016 a-b; Aversa et al., 2016 a-o, 2017 a-e).

Metal ions act as an enzyme co-factored effect on signaling pathways to stimulate the metabolic effect on tissues engineering (Hoppe et al., 2011). Metal ions play important role as therapeutic agent in hard and soft tissue engineering. Ca and P ions are the part of the main component of inorganic apatite of human bone (Ca10(PO4,CO3)6OH2) (Bielby et al., 2005; Habib et al., 2007; Hoppe et al., 2011; Mouriño et al., 2012).

Bioactive Material has ability to release inorganic ions and contributes in natural bone metabolism (Bielby et al., 2005; Habib et al., 2007; Karageorgiou and Kaplan, 2005; Maeno et al., 2005).

Bioactive Materials

First Generation Biomaterials

Early biomaterials were used to replace damage or missing living structure that’s why biomaterial assumed to have compatible physical properties similar to the natural structure with minimal tissue reaction or toxic effect on tissue. Most of the materials were bioinerts (Sundar et al., 2012; Petrescu et al., 2015).

Second Generation Biomaterials

During early 70s bioactive material such as bioactive glass, ceramic glass and composites were introduced in the field of tissue engineering. These materials make a chemical bond with natural tissue and elicit tissue generation by enhancing production of tissue forming cells, through the ion dissolution process from the surface of materials (Sundar et al., 2012).

Second Generation bio materials also includes resorbable biomaterial such as calcium phosphates. It has ability to breaks down chemically and reabsorb to equivalent ratio of that regrowth tissue (Shirtliff and Hench, 2003; Gramanzini et al., 2016).

The material tissue bonding involves 11 steps of reacting. First 5 steps involves surface material reaction of ion exchange which followed by poly condensation reaction. This surface reaction provides a layer of hydroxyapatite layer that equivalent to the inorganic layer of natural bone tissue.

Third Generation Biomaterials

The concept of resorbable materials and bioactive material is merged to form third generation bioactive resorbable glass and ceramic material that can activate gens in tissue engineering (Shirtliff and Hench, 2003). Bioactive materials are used in powder, solution or micro particles form to stimulate tissue repair (Sorrentino et al., 2007; 2009). The release of chemicals in the form of ions dissolution from the bioactive materials and growth factors such as bone morphogenic protein that enhance the cell proliferation (Hench and Polak, 2002; Sundar et al., 2012) due to osteo conduction and osteoproduction process. The surface reaction of material that gives ions dissolution responsible in intracellular and extracellular response (Hench and Polak, 2002; Sundar et al., 2012).

Cell Cycle and Gene Activation

Osteoblastic cell differentiation and proliferation is controlled by the activation of a synchronized sequence of genes which undergo mitosis of cells after that the synthesis of extracellular matrix by bone cells occur (Polak and Hench, 2005). There is genetic control of cellular response to the bioactive material also present. When human Osteoblastic cells expose to ionic dissolution of bioactive material seven families of genes are activated. These activated genes express protein that effect on differentiation and proliferation of osteoblast (Sundar et al., 2012). The ion dissolution of bioactive materials that enhance cell repair at molecular level by creating scaffold on the damage bone tissue (Polak and Hench, 2005; Sundar et al., 2012). After construction of scaffold it is necessary to build blood vessels in it.

Table 1. First, second and third generations of bioactive materials with their applications

Generation Material Difference in function

First Bio inert Replace tissues without

generation reaction with tissues

Second Bioactive Making chemical bond

generation with tissues

Third generation Bioactive plus Gene activation


Third Generation bioactive materials are also useful in making vascularization in scaffold.

Third Generation Bioactive materials work by the activation of genes for rapid differentiate and proliferation of cells for healing at molecular level.

This is revolution in molecular biology it makes connection between inorganic materials with living tissue (Sundar et al., 2012).

The materials used in scaffold are synthetic polymers such as Polysaccharides, Poly (x-hydroxy ester), hydrogels or thermoplastic elastomers (Boccaccini and Ma, 2014; Rezwan et al., 2006) and other important materials are bioactive ceramic such as calcium phosphate and bioactive glasses or glass ceramic (Boccaccini and Ma, 2014; Rezwan et al., 2006) composites of polymers and ceramics are being produced to enhance mechanical scaffold stability and to improve tissue interaction (Bielby et al., 2005; Kim et al., 2004).

Synthetic Polymers

Polymers are the chain of molecules which has repeated unit in it. Repeated unit make polymers differ it from other small molecules. Monomer, the elimination of small molecules such as water and HCL during polymerization (Ratner et al., 2004).

Linear polymers with variety of molecular weight are used for biomedical application. But molecular weight may depend on the polymers chain integration with other hydrogen bond which give it more strength. Higher molecular weight corresponds to more physical properties melting viscosity also increases with respect to the molecular weight.

The syntheses of polymers are of two methods, additional polymerization chain reaction and condensation polymerization (Ratner et al., 2004).

Polymers are in amorphous or semi crystalize form. Its crystalline state can be increased by short side group and chain regularity. Its crystallization increase its mechanical property which determines the thermal behavior and also increases its fatigue strength (Ratner et al., 2004). The deformation behavior is the key factor for tensile strength. Amorphous, rubbery polymers are soft and extensible. Semi crystalline polymers are less extensive.

The most important property of polymers to use as biomaterial is the stress at the point of breakage or failure. Failure means catastrophic (complete breakage). The fatigue behavior is also making polymer to use as biomaterials. In liquid or melted state polymer has high thermal energy. Viscoelastic property also represented by its thermal behavior (Perillo et al., 2010). Linear amorphous Polymer with increase temperature 5-10°C, converted from stiff glass to leathery material (Boccaccini and Ma, 2014; Ratner et al., 2004).

Saturated Polymer

The most often used for 3D scaffold biodegradable synthetic polymers, saturated polymers includes Poly-x-hydroxy esters, poly (lactic acid) PLA and poly (glycolic acid) (PGA) as well as poly (lactic-Co glycolide) (PLGA) Co polymer (Rezwan et al., 2006).

Due to the chemical properties of these polymers which allows hydrolytic degradation through de-esterification. As degradation occurs, the mono

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