**1. Introduction**

Bone is the second most transplanted tissue in the world, second only to blood [1]. Hundreds of millions of people worldwide are affected by musculoskeletal conditions which are on the increase with aging population and lifestyle. Bone is a critical tissue within the vertebrates. It is a dynamic organ with many functions. It provides load bearing, body structural support onto which musculature is attached, protection for vital organs and soft tissues (brain, heart, lung, etc), and enables locomotion and motor functions. It is the host of important biological processes critical cells such as postnatal stem cell populations that support hematopoiesis, myelopoiesis, and skeletogenesis. Bone is also responsible for storing and supplying of minerals such as calcium and phosphate [2]. Native bone is a connective tissue made of two predominant components: a mineralized and an unmineralized phase. The mineralized inorganic phase contains mainly crystalline apatitic calcium phosphate (70%), water (20%), and the non-mineralized organic phase (10%) is made of fibrous type I collagen, proteins, polysaccharides and lipids (**Figure 1**) [3].

#### *Chitin and Chitosan - Physicochemical Properties and Industrial Applications*

#### **Figure 1.** *Cancellous and cortical bone microstructure.*

This natural biological "composite" [4] has many biological features such osteoconductivity, osteoinductivity, osteogenicity and is subject to continuous remodeling and regeneration process through osteoclastic and osteoblastic activities. The hard tissues in vertebral is not uniform tissue it could be dense and hard like dental enamel and cortical bone or spongy and highly porous like a foam as the cancellous bone.

Hard tissue repair is a multifaceted, coordinated physiological process that requires new tissue formation and resorption, eventually returning the fractured bone, for example, to its original state. Bone has the capacity of regenerating itself, especially in noncritical size defects. However, large bone defects caused by trauma, injuries, tumor resections, infections, would not heal spontaneously, and would require a bone substitute grafting material to fill the bony void for proper regeneration to take place [5].

The first documented bone transplant was performed in 1668 by a Dutch surgeon, Jacob van Meekeren, when he used dog cranium (xenograft) to repair a soldier's skull defect. The success of the grafting technique was discovered later when the soldier came back asking for removal of the "dog bone," because it cost him excommunication from the church. Meekeren discovered then that the bone healed so well it was impossible to remove the graft. The first human to human bone graft performed was in 1880 by Scottish surgeon William Macewan. He replaced the infected humerus of a 4- year-old boy with a tibia graft taken from a child with rickets [6]. The use of synthetic bone grafts could be traced back to as early as 1892 when Dreesmann reported on the results of filling osseous defects with calcium sulfate [7]. Since then, hundreds of thousands of bone grafting surgeries have been performed on humans and animals.

In 1980, major health issues related to safety of bone donors (Aids and Hepatitis) has brought the associated problems of contamination and spread of dangerous diseases to the spotlight. Some years later, (1986) the discovery of the contagious pandemic bovine spongiform encephalopathy (BSE) and the porcine endogenous retrovirus (PERVs) [8], made more obvious the necessity of alternative safe bone substitute materials in bone transplant procedures. This provided a considerable boost to research and development in the usage of synthetic bone substitutes as a safe and an affordable alternative to natural bone materials. Since then, many technologies have been adopted and used to produce bone-like products with tailored biological, physical, and chemical properties, including plasma projection [9], sol-gel [10], composites, foaming, nanotechnology,

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**Table 1.**

Xenograft (demineralized)

Metal and polymeric based implants

Cells, growth factors, BMP, PePgen, Ifactors

*Chitosan Based Biocomposites for Hard Tissue Engineering*

3D-printing techniques, additive manufacturing [8, 11] and some biological therapies that involve usage of growth factors, proteins, peptides, stem cells or

Nowadays, many options are available to regenerate or replace bone in clinical conditions. The main clinical approach is using a natural or a man-made bone or bone induction materials (see **Table 1**). There are three categories of natural bone, a large family of synthetic bone substitutes and biological factors-based approaches. (**Table 1**). In bone regeneration therapy, the gold standard has been the autograft (patient's

own harvested bone) [1, 9, 14]. However, autograft treatment is not always possible or even the best option. It is also limited by the volume of bone that can be harvested from the iliac crest and subsequently transplanted into the defect site. Furthermore, post-operative complications include morbidity at the harvest site, chronic pain, infection, local hematoma and, in some cases, remodeling issues of

The established safety, efficacy, and abundance of supply of advanced synthetic bone-substitute materials made them stand as an attractive and effective alternative to the autogenous bone gold standard. On-going research in the field and a growing body of clinical data points to an even more promising future for these substitutes. Some calcium phosphate bioceramics, for example, display remarkable clinical performances and research and technological developments keep intensifying with the aim of bridging the gap to the ideal bone grafting material which would possess the three principal characteristics of the gold standard: osteogenicity, osteconduction and osteoinduction. In human and animal medicine, orthopedic and dental surgeries, alloplastic biomaterials for hard tissue repair are divided in two categories that can be classi-

i.**The bio-inert materials category:** They can be permanent or implanted for short-term and removed or replaced, like metallic dental or orthopedic implants. They are generally made of titanium, stainless-steel, nickel, zirconia or made of synthetic polymers, e.g., polymethylmethacrylate (PMMA)

> Limited supply Donor site, inflammation and chronic pain, site morbidity, Requires a second surgery, No mechanical

• Reduced osteogenic, -Immune rejections, Disease transmission (AIDS,

• Reduced osteoinductive, osteogenic properties, Immune rejections, Disease

Prion), Slow resorption

transmission (Mad cow)

(monomer, metal debris)

No mechanical

applications, side effects (BMP)

Natural Requires biomaterial carrier, Limited

Do not have any biological factor,

Not biodegradable, Bioinert, some toxicity

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

gene therapies [12, 13].

the implanted bone [8].

fied as per their biological responses:

or Polyether ether ketone (PEEK).

Autografts No biological risk, osteogenic,

Allograft Greater supply compared to

Synthetic (Alloplastic) Pure, Unlimited supply,

*Available therapies used to regenerate/support bone tissue.*

cells

**Category Advantage Limitations**

autograft tissue

properties

applications

osteoinductive, contain live

Unlimited supply could be osteoconductive

Longer shelf life, tuneable

Biocompatible, Load bearing

*Chitin and Chitosan - Physicochemical Properties and Industrial Applications*

This natural biological "composite" [4] has many biological features such osteoconductivity, osteoinductivity, osteogenicity and is subject to continuous remodeling and regeneration process through osteoclastic and osteoblastic activities. The hard tissues in vertebral is not uniform tissue it could be dense and hard like dental enamel and cortical bone or spongy and highly porous like a foam as the

new tissue formation and resorption, eventually returning the fractured bone, for example, to its original state. Bone has the capacity of regenerating itself, especially in noncritical size defects. However, large bone defects caused by trauma, injuries, tumor resections, infections, would not heal spontaneously, and would require a bone substitute grafting material to fill the bony void for proper regeneration to take place [5]. The first documented bone transplant was performed in 1668 by a Dutch surgeon, Jacob van Meekeren, when he used dog cranium (xenograft) to repair a soldier's skull defect. The success of the grafting technique was discovered later when the soldier came back asking for removal of the "dog bone," because it cost him excommunication from the church. Meekeren discovered then that the bone healed so well it was impossible to remove the graft. The first human to human bone graft performed was in 1880 by Scottish surgeon William Macewan. He replaced the infected humerus of a 4- year-old boy with a tibia graft taken from a child with rickets [6]. The use of synthetic bone grafts could be traced back to as early as 1892 when Dreesmann reported on the results of filling osseous defects with calcium sulfate [7]. Since then, hundreds of thousands of bone grafting surgeries have been

In 1980, major health issues related to safety of bone donors (Aids and Hepatitis) has brought the associated problems of contamination and spread of dangerous diseases to the spotlight. Some years later, (1986) the discovery of the contagious pandemic bovine spongiform encephalopathy (BSE) and the porcine endogenous retrovirus (PERVs) [8], made more obvious the necessity of alternative safe bone substitute materials in bone transplant procedures. This provided a considerable boost to research and development in the usage of synthetic bone substitutes as a safe and an affordable alternative to natural bone materials. Since then, many technologies have been adopted and used to produce bone-like products with tailored biological, physical, and chemical properties, including plasma projection [9], sol-gel [10], composites, foaming, nanotechnology,

Hard tissue repair is a multifaceted, coordinated physiological process that requires

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cancellous bone.

*Cancellous and cortical bone microstructure.*

**Figure 1.**

performed on humans and animals.

3D-printing techniques, additive manufacturing [8, 11] and some biological therapies that involve usage of growth factors, proteins, peptides, stem cells or gene therapies [12, 13].

Nowadays, many options are available to regenerate or replace bone in clinical conditions. The main clinical approach is using a natural or a man-made bone or bone induction materials (see **Table 1**). There are three categories of natural bone, a large family of synthetic bone substitutes and biological factors-based approaches. (**Table 1**).

In bone regeneration therapy, the gold standard has been the autograft (patient's own harvested bone) [1, 9, 14]. However, autograft treatment is not always possible or even the best option. It is also limited by the volume of bone that can be harvested from the iliac crest and subsequently transplanted into the defect site. Furthermore, post-operative complications include morbidity at the harvest site, chronic pain, infection, local hematoma and, in some cases, remodeling issues of the implanted bone [8].

The established safety, efficacy, and abundance of supply of advanced synthetic bone-substitute materials made them stand as an attractive and effective alternative to the autogenous bone gold standard. On-going research in the field and a growing body of clinical data points to an even more promising future for these substitutes. Some calcium phosphate bioceramics, for example, display remarkable clinical performances and research and technological developments keep intensifying with the aim of bridging the gap to the ideal bone grafting material which would possess the three principal characteristics of the gold standard: osteogenicity, osteconduction and osteoinduction.

In human and animal medicine, orthopedic and dental surgeries, alloplastic biomaterials for hard tissue repair are divided in two categories that can be classified as per their biological responses:

i.**The bio-inert materials category:** They can be permanent or implanted for short-term and removed or replaced, like metallic dental or orthopedic implants. They are generally made of titanium, stainless-steel, nickel, zirconia or made of synthetic polymers, e.g., polymethylmethacrylate (PMMA) or Polyether ether ketone (PEEK).


#### **Table 1.**

*Available therapies used to regenerate/support bone tissue.*

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 and applications.

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 and limitation of the technology.
