**2. Craniomaxillofacial bone defects and reconstruction strategies**

Earlier it was assumed that strategies developed to augment appendicular skeletal repair can be directly translated for craniofacial reconstruction. But the use of advanced techniques such as intravital imaging, fluorescence trapping and wholebody optical imaging has revealed that calvarial bone possess a larger normalized blood volume fraction and enhanced bone remodeling activity as compared to long bones [5]. However, the traditional therapeutic modalities of reconstruction such as autologous bone grafting present myriad limitations of restricted availability of donor-site, morbidity and significant complications in restoring the three-dimensional structure of craniomaxillofacial bone [14, 16].

For instance, cleft lip/palates, the most common oral and craniomaxillofacial birth defects are addressed by the standard clinical procedures of surgery involving reconstruction of the mouth roof to separate the nasal cavity from the oral cavity. Two flap palatoplasty and Furlow double-opposing Z-plasty are the two common surgical procedures that involve suturing of soft tissues to close the wound. However, complete restoration of severe cleft palate still remains a challenge due to non-availability of autologous soft tissues [17].

Furthermore, craniomaxillofacial osseous reconstructive surgeries are performed using autologous reconstruction techniques such as free flaps (fibula and ilia crest) instead of regional flaps (pectoralis major muscle with ribs, trapezius, temporalis muscle with calvaria), because of problems associated with morbidity of regional flaps, though the regional flaps provide for the best candidate in terms of tissue matching [12]. Therefore, membranes have gained extensive importance in the field of oral and maxillofacial surgery, for their use in guided bone regeneration (GBR). These membranes function as a barrier between the fast proliferating soft tissues (fibrous connective tissue or epithelium) and slow proliferating hard tissue (bone) [18]. Membrane systems that are clinically applied do not sufficiently prevent bacterial infections. To address this problem the membranes were fabricated using film casting method, which generates a mechanical barrier to prevent bacterial transmigration through the membrane [19]. Furthermore, as these membranes are either allogenic or xenogenic, a potential risk of transmission of infection along with legal, ethical or religious limitations should be taken into consideration [18].

It has been suggested that the use of scaffold with tailored geometries and surfaces may promote bone regeneration in GBR [18]. Furthermore, finite element analysis of dental implants during mastication has revealed that the surrounding alveolar bone, that supports the dental implant, experiences a compressive stress of 62 MPa while experiencing an applied bite force of 146 N. These compressive forces may go as high as 122 MPa and therefore the bone graft is expected to fully integrate and eventually replace by the host bone tissue [9].

The last decade has seen an extensive progress in craniofacial bone tissue engineering modalities that couple biomaterials with growth factors or stem cell-based therapies [14]. Basically, the bone grafting materials can be divided into autologous, allogenic, xenogenic and alloplastic [9]. However, transplantation of autograft or allograft has limited applicability due to low availability, donor site morbidity, risk of infection, persistent pain, hemorrhage and subsequent graft failure [4, 20, 21]. Also autografts, allografts and xenografts are brittle due to the post extraction processing [9]. Additionally, the traditional procedures of implantation employed metal and metal alloys for repairing of bone defects due to their excellent mechanical properties. However, it was lately realized that the elastic modulus of these metals including stainless steel and titanium-based alloys was much higher than that of human bones, leading to stress-shielding. Moreover, corrosion and release of ionic species from these metal implants has also been found to induce inflammatory responses, cell apoptosis and foreign body reaction [22]. One of the studies demonstrated that a significant amount of time spent in contouring the titanium or absorbable scaffolds (to fit the irregularity of craniomaxillofacial bones), increases the overall risk due to extended operation time. Moreover, over-bending and lack of passive fitting of titanium eventually leads to fatigue fractures [23].

Tissue engineering has been found to address some of these limitations through development of biomimicking 3D matrices [4]. The repair of complex craniofacial bone defects is challenging and the success mainly depends on the choice of reconstructive method [24]. In order to design, develop, recreate and reconstruct a tissue defect, bioimplants (cell-based or cell-free) have emerged as a promising tool. Strategies of bioimplantations require exhaustive knowledge of diverse field such as chemistry, material science, biology, medicine, and engineering. Additionally, the actual designing requires a scaffold material, cells and cell growth factors in place. We have summarized both the knowledge based and material-based requirements in **Figure 1**.

However, placement of implants in the oral cavity encounters a major challenge of insufficient bone volume, as the dental implants cannot be placed in atrophic jaw bone. Therefore, the success of bone reconstruction/regeneration procedures extensively depends on the fact that whether the implant site can firmly support the bone graft material [25]. Moreover, the dentoalveolar defects require a rapidly resorbing matrix to avoid wound dehiscence, exposure and subsequent microbial contamination [26].

*Advances in Tissue Engineering Approaches for Craniomaxillofacial Bone Reconstruction DOI: http://dx.doi.org/10.5772/intechopen.94340*

**Figure 1.** *Pre-requisites for tissue engineering.*

Based on several such investigations and observations the specific expectations from a craniofacial scaffold can be enlisted as follows:


The choice of biomaterial and method of fabrication are the two critical factors that shape the use of scaffold. Biomaterials are the materials that interface with biological systems and can be classified on the basis of chemical and physical composition, biodegradability, type of origin and generations of modifications. Based on chemical composition biomaterials are classified into ceramics, polymers and composites [1].


The methods of fabrication are directly dependent on the bulk and surface characteristics of the biomaterials and the projected function of the scaffold. The techniques should be capable of processing different microstructures with strict monitoring of pore size, porosity and pore interconnectivity [31]. The fabrication approach should include design techniques that can rigorously control both the exterior shape of the scaffold and interior porous architecture, to provide the right balance between load bearing strength and delivery of biomolecules [13].

#### **3. Biomaterials for bone tissue engineering**

As mentioned in the previous section the biomaterials used for bone tissue engineering are classified as ceramic, polymers and composites. According to the International Union of Pure and Applied Chemistry, the materials are further are classified into three categories: microporous (< 2 nm), mesoporous (2–50 nm) and macroporous (> 50 nm), on the basis of porosity. The porous materials suitable for fabrication of bone implants should have pore sizes ranging from micropore to mesopore scale [32]. Their porous structure provides them a higher surface area to volume ratio, thus enhancing their drug loading capacity [33].

#### **3.1 Bioceramics**

Bioceramics such as hydroxyapatite (HA), α and β tri-calcium phosphate, demineralized bone matrices, calcium carbonates, calcium sulfates and bioactive glasses have recently gained importance as novel treatment for craniomaxillofacial bone reconstruction and cleft lip/palate repair [13].

*Advances in Tissue Engineering Approaches for Craniomaxillofacial Bone Reconstruction DOI: http://dx.doi.org/10.5772/intechopen.94340*


ease of P-O-P bond hydration), that is strongly dependent on their composition. Their dissolution rate can be tailored by adding appropriate metal oxides (TiO2, CuO, NiO, MnO, Fe2O3) and these bioglasses can be utilized as controlled release vehicles [33]. Calcium PGs scaffolds have been demonstrated to regenerate bone and cementum when implanted in 1-wall intrabony alveolar defects of beagle dogs [39].

8.Mesoporous materials such as bioactive glasses (BG) are popularly used as implant materials for alveolar bone regeneration. For synthesis of mesoporous BGs, surfactant is introduced as the structure directing agent, during the solgel process of the glass. The surfactant is removed at the end of the process by calcination or extraction and the micelles previously occupied by the surfactant are replaced by mesopores. For the purpose of tissue engineering mesoporous bioglass can be coated on the surface of polymeric scaffold; incorporated in a polymeric matrix in the form of particles; fabricated as scaffold and coated with a polymer [33]. Mesoporous BG nanolayers (thickness 100 nm), created by spin coating on the surface of β-TCP scaffolds have been found to significantly improve osteogenesis [40].
