**2. Chitosan biomedical and regenerative features**

Many biomaterials are available in the market for medical, cosmetic, and pharmaceutical applications. In tissue engineering, synthetic or natural biopolymers make one of the fastest growing niche segments of biomaterials. The growth is probably driven by the wide range of possibilities offered by their chemistry for different applications and the increasing demand of the biotechnology industry market.

After cellulose, chitin is the most abundant and beneficial structural non soluble organic biopolymers found on Earth. Chitin, a long polymer of N-acetylglucosamine, is the primary compound naturally found in the exoskeleton of arthropods such as crabs and shrimps, and in the cell membranes of fungi, yeasts, and other microorganisms. Deacetylation of some of acetylglucosamine units of chitin has brought a very interesting polysaccharide biopolymer to the biotechnology field, especially the biomedical area; chitosan (CS). CS is a polysaccharide composed of successive acetylglucosamine and N-glucosamine units, where the number of N-glucosamine units is called the degree of deacetylation (DDA) [15] (usually 55% < DDA < 99%). CS macromolecules gained increasing attraction during the last three decades in research and industrial fields, especially in water treatment processes, pharmaceutical and biomedical engineering. Its chemistry with three reactive functional groups of amin/acetamido groups and primary and secondary hydroxyl groups allows for a large spectrum of possible chemical modifications and substitutions of its functional groups (ex: OH, and NH2 by -COCH3, -CH3, -CH2COOH, SO3H, -PO(OH)2, etc) [16, 17]. This improves and creates additional functional properties and features and facilitates its adaptability to different applications such as antimicrobial agency in food processing and its packaging industries, as a fungicide, as a blood sugar and pressure reducing agent, as a dietary supplement. Other applications are also found in veterinary medicine, microbiology, immunology, and agriculture, and most importantly, in highly innovative areas such as pharmaceuticals (e.g., drug delivery systems) and tissues/organs regeneration medicine in the biomedical field [18].

The global chitosan market size was valued at USD 6.8 billion in 2019 and is expected to expand and reach USD 28.93 billion by 2027. After water treatment, the second largest market is the pharmaceutical and biomedical market [19].

In the chitosan manufacturing process, the degree of deacetylation (DDA) and the molecular weight (MW) are critical parameters, as the final properties and applications of the CS biomaterial will depend on it.

**79**

**Table 2.**

Adequate resistance and mechanical properties

The proper design, size, and shape of the scaffolding

*Main characteristics that biomaterial should have.*

*Chitosan Based Biocomposites for Hard Tissue Engineering*

structure and function of damaged organs or tissues [24–34].

**Characteristics Description of the characteristic**

Many parameters could affect the degree of deacetylation (DDA) and, consequently, the physical, chemical, and biological properties of chitosan. Parameters include the source raw material (animal, insect, fungi, mollusca, cephalopod, etc) [20] and processing conditions (pH, temperature, processing time). After manufacturing, batch parameters such as the degree of deacetylation (DDA), molecular weight (MW), molecular mass (MM), viscosity, solubility, pH, purity, protein content, endotoxin, ash content, contaminants should be carefully evaluated to ensure a safe and an adequate utilization. Chitosan and chitosan derivative biopolymers were found to be non-toxic, biocompatible, osteogenic [21, 22] antibacterial, biodegradable, bioresorbable, antioxidant, immunoenhancing and anticancer [23]. In addition, they were found to promote cell adhesion, proliferation, and differentiation, which are important processes in tissue repair. It is, then, no coincidence that chitosan is one of the most extensively investigated polymers in tissue engineering to replace or restore the

In the biomedical field, particularly in the tissue engineering domain, the main goal is to replace or substitute, repair maintain or improve tissue function through the use of isolated living cells, cells substitute tissue inducers on/or in a matrix to repair and regenerate tissue by combining engineering principles and life sciences [24, 25]. To reach that goal, there are critical properties that candidates biomaterials

These imply that the biomaterial should allow the proliferation, adhesion and differentiation of the cells, the basic elements of any living tissue. Chitosan biomaterial can be processed in different forms such as film, mesh and fibers, freeze dried beads or scaffolds, as composite, as thermal, light, or chemical sensitive injectable gel solution or crosslinked polymer. Alone or grafted with other biopolymers (e.g., alginate, polyvinyl alcohol, polyacrylic acid, etc) [27]. Among all the possibilities, researchers and physicians have to select the formulations that are most compatible with the targeted tissue environment and function.

Biocompatibility They must be accepted by the receptor and must not lead to rejection mechanisms because of its presence. Absorbability and degradability Absorbable, with controllable degradation and resorption rate to be the

Not to be toxic or carcinogenic Its degradation products cannot cause local or systemic adverse effect on a biological system Chemically stable Chemical modifications not being present in a biological system

scheduled time to regenerate tissue Chemically adequate surface To have a chemically adequate surface for cell access, proliferation and

of the receiving tissue to regenerate or repair.

cell differentiation

same as the in vitro and in vivo cell/tissue growth

implant or biodegradable in nontoxic products, at least during the

Resistance and mechanical properties, superficial characteristics, fatigue time, and weight, according to the receptor tissue needs, as well

Which allows having a structure with properties according to the needs

*DOI: http://dx.doi.org/10.5772/intechopen.98468*

**2.1 Chitosan and hard tissues**

need to have. They are summarized in **Table 2**:

*Chitosan Based Biocomposites for Hard Tissue Engineering DOI: http://dx.doi.org/10.5772/intechopen.98468*

*Chitin and Chitosan - Physicochemical Properties and Industrial Applications*

and applications.

and limitation of the technology.

tion medicine in the biomedical field [18].

applications of the CS biomaterial will depend on it.

**2. Chitosan biomedical and regenerative features**

ii.**The bioactive biomaterials**: They are mostly resorbable at different levels. It is a large family of bone substitutes that vary in type and composition such as bioglass, calcium sulfate, calcium phosphate bioceramics (CaP), biopolymers and biocements. They could also be in tunable forms such as powder, granules, blocs, paste or injectables. They offer a dynamic choice of material

In this chapter we will review some interesting development and advancement made in biomaterial sciences in regeneration of natural hard tissues through man made products. We will focus on the polysaccharide polymer, chitosan, similar to the organic phase of natural bone and cartilage and calcium phosphate based bioceramics, similar to the inorganic phase of natural bone. We will present some tested biocomposites formulations made out the combination of the two biomaterials to mimic the composition and structure of natural bone and discuss the success

Many biomaterials are available in the market for medical, cosmetic, and pharmaceutical applications. In tissue engineering, synthetic or natural biopolymers make one of the fastest growing niche segments of biomaterials. The growth is probably driven by the wide range of possibilities offered by their chemistry for different applications and the increasing demand of the biotechnology industry market. After cellulose, chitin is the most abundant and beneficial structural non soluble organic biopolymers found on Earth. Chitin, a long polymer of

N-acetylglucosamine, is the primary compound naturally found in the exoskeleton of arthropods such as crabs and shrimps, and in the cell membranes of fungi, yeasts, and other microorganisms. Deacetylation of some of acetylglucosamine units of chitin has brought a very interesting polysaccharide biopolymer to the biotechnology field, especially the biomedical area; chitosan (CS). CS is a polysaccharide composed of successive acetylglucosamine and N-glucosamine units, where the number of N-glucosamine units is called the degree of deacetylation (DDA) [15] (usually 55% < DDA < 99%). CS macromolecules gained increasing attraction during the last three decades in research and industrial fields, especially in water treatment processes, pharmaceutical and biomedical engineering. Its chemistry with three reactive functional groups of amin/acetamido groups and primary and secondary hydroxyl groups allows for a large spectrum of possible chemical modifications and substitutions of its functional groups (ex: OH, and NH2 by -COCH3, -CH3, -CH2COOH, SO3H, -PO(OH)2, etc) [16, 17]. This improves and creates additional functional properties and features and facilitates its adaptability to different applications such as antimicrobial agency in food processing and its packaging industries, as a fungicide, as a blood sugar and pressure reducing agent, as a dietary supplement. Other applications are also found in veterinary medicine, microbiology, immunology, and agriculture, and most importantly, in highly innovative areas such as pharmaceuticals (e.g., drug delivery systems) and tissues/organs regenera-

The global chitosan market size was valued at USD 6.8 billion in 2019 and is expected to expand and reach USD 28.93 billion by 2027. After water treatment, the

In the chitosan manufacturing process, the degree of deacetylation (DDA) and the molecular weight (MW) are critical parameters, as the final properties and

second largest market is the pharmaceutical and biomedical market [19].

**78**

Many parameters could affect the degree of deacetylation (DDA) and, consequently, the physical, chemical, and biological properties of chitosan. Parameters include the source raw material (animal, insect, fungi, mollusca, cephalopod, etc) [20] and processing conditions (pH, temperature, processing time). After manufacturing, batch parameters such as the degree of deacetylation (DDA), molecular weight (MW), molecular mass (MM), viscosity, solubility, pH, purity, protein content, endotoxin, ash content, contaminants should be carefully evaluated to ensure a safe and an adequate utilization.

Chitosan and chitosan derivative biopolymers were found to be non-toxic, biocompatible, osteogenic [21, 22] antibacterial, biodegradable, bioresorbable, antioxidant, immunoenhancing and anticancer [23]. In addition, they were found to promote cell adhesion, proliferation, and differentiation, which are important processes in tissue repair. It is, then, no coincidence that chitosan is one of the most extensively investigated polymers in tissue engineering to replace or restore the structure and function of damaged organs or tissues [24–34].

## **2.1 Chitosan and hard tissues**

In the biomedical field, particularly in the tissue engineering domain, the main goal is to replace or substitute, repair maintain or improve tissue function through the use of isolated living cells, cells substitute tissue inducers on/or in a matrix to repair and regenerate tissue by combining engineering principles and life sciences [24, 25]. To reach that goal, there are critical properties that candidates biomaterials need to have. They are summarized in **Table 2**:

These imply that the biomaterial should allow the proliferation, adhesion and differentiation of the cells, the basic elements of any living tissue. Chitosan biomaterial can be processed in different forms such as film, mesh and fibers, freeze dried beads or scaffolds, as composite, as thermal, light, or chemical sensitive injectable gel solution or crosslinked polymer. Alone or grafted with other biopolymers (e.g., alginate, polyvinyl alcohol, polyacrylic acid, etc) [27]. Among all the possibilities, researchers and physicians have to select the formulations that are most compatible with the targeted tissue environment and function.


#### **Table 2.**

*Main characteristics that biomaterial should have.*

Hard tissues like bone and cartilage require some specific formulations, with specific chemical and physical properties to withstand the regeneration of the native hard tissues process.
