**Abstract**

Trauma, congenital abnormalities and pathologies such as cancer can cause significant defects in craniofacial bone. Regeneration of the bone in the craniofacial area presents a unique set of challenges due to its complexity and association with various other tissues. Bone grafts and bone cement are the traditional treatment options but pose their own issues with regards to integration and morbidity. This has driven the search for materials which mimic the natural bone and can act as scaffolds to guide bone growth. Novel technology and computer aided manufacturing have allowed us to control material parameters such as mechanical strength and pore geometry. In this chapter, we elaborate the current status of materials and techniques used in fabrication of scaffolds for craniomaxillofacial bone tissue engineering and discuss the future prospects for advancements.

**Keywords:** tissue engineering, regenerative medicine, bone regeneration, 3D printing, craniomaxillofacial, additive manufacturing, scaffold, polymer, synthetic polymer, biopolymer, bone defect

### **1. Introduction**

The incredible capacity of human body to regenerate is governed by factors such as size of the defect, requirement of growth hormones and the type of the tissue [1]. Any injury to a tissue beyond the critical size needs external support for regeneration. A defect is considered as a critical size defect when it does not spontaneously heal on its own and requires intervention [2]. This approach of mitigating and reconstructing the damaged or injured tissue is referred to as regenerative medicine or tissue engineering [1].

Bone is considered to be the second most engineered tissue, which undergoes degeneration due to tumor surgeries, osteoporosis, trauma etc. [3]. Natural bone matrix is composed of organic (collagen) and inorganic (apatite) materials. By weight bone contains 30% collagen matrix, 60% mineral and 10% water. The unique modulus of bone, falls between conventional plastics and ceramics, and

is primarily determined by a unique interpenetrating arrangement of collagen and apatite at the nanoscale. Naturally, the process of bone healing is determined by the size of the wound. This process in turn is directed and stimulated by wellbalanced biological and microenvironmental cues. In case of large bone defects the fibrous tissue regenerates faster than the bone tissue and becomes dominant at the defect site. Excess of fibrous tissue does not compensate for the loss of mechanical strength. Therefore, repair of large bone defects necessitates implantation of a replacement material to facilitate bone healing [4].

Calvarial and long bones are unique and distinct from each other in terms of development, structure and function. From a developmental point of view, intramembranous ossification is dominant in skull bone formation whereas long bone formation majorly occurs via endochondral ossification. These distinctions require customized tailoring of specific strategies for either calvaria or long bone repair. Calvarial bones are required to withstand impact forces whereas long bones must withstand the bending and twisting movements and therefore horizontal grafting and vertical bone augmentation techniques need to be developed for reconstruction purposes respectively [5, 6].

The craniofacial region includes facial skin, muscles, bone, tendons, ligaments, nerves and blood vessels. The craniomaxillofacial bones consist of cranial and facial bones. Cranial bones enclose the brain and protect it, whereas facial bones such maxillary and mandible act as load bearing bones for dental region [7]. The bone tissue thus encompasses mandible, auditory ossicles, neuro cranium (protects the brain) and splanchnocranium (supports the face) [8]. Whereas, the cartilaginous part of the craniomaxillofacial region is primarily constituted by temporomandibular joint disc, auricle and nasal regions of the craniofacial cavity [3]. Moreover, the dental tissue in the craniofacial region includes both hard structures (enamel, cementum and dentin) and soft tissue component (pulp cavity) [7], which together make up the structure of tooth. Tooth is embedded into the maxillary and mandibular bones, which together constitutes the alveolar bone. It has been found that the cortical thickness of the alveolar bone is 2.1–2.4 mm and a density is 1.64–1.75 mg/cm3 whereas the compressive strength of cancellous bone in the mandibular region is in the range of 0.2–10.44 MPa (average 3.9 ± 2.7 MPa, depending on the bone density, age and gender) [9].

Tooth defects or tooth loss caused by endodontic diseases, periodontal disease, tumor, trauma and variety of genetic disorders require dentin and dental pulp tissue regeneration. However, the current available treatments involve replacement of lost tooth by artificial dentition or dental implants. Thus, extensive research is required to achieve reconstruction of such craniofacial and dental tissue defects [10]. The reconstruction therapy for critical bone defects should address the post-surgical side effects of slow or deficient bone recovery, graft rejection and low osseointegration [11].

Periostium is a major source for osteoprogenitor cells whereas dura mater contains multipotent mesenchymal stem cells that facilitate skull bone healing through paracrine signaling, indicating that the indigenous surrounding tissues of the craniomaxillofacial skeleton such as dura mater, periostium, suture and bone marrow themselves play an important role in healing processes [5]. As the craniomaxillofacial region is associated with a variety of vital functions such as vision, hearing, speech, mastication, breathing and normal brain function, the injuries of this region caused due to trauma, tumor surgery or genetic defects results in critical defects which are difficult to reconstruct because of complexity of anatomical structure, variety of tissue specific requirements and restoration of esthetic facial features, seeking for facial harmony and most perfect symmetry [8, 12–14]. Furthermore, maxillectomy defects are more complex when critical structures such as the orbit, globe and cranial base are involved [12]. Moreover, applications of tissue engineering procedures in this region require additional understanding of

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

complex developmental processes, physiology, molecular pathways and remodeling characteristics [14]. Thus, an ideal tissue engineering approach to repair craniomaxillofacial defects should result in a complete biological tissue capable of adapting to physiological cues and overcoming the limitation of prosthetics [15].

Extensive research in the field of tissue engineering over the last two decades has revolutionized our approach toward regenerative therapies. Over the years, this approach has progressed in terms of biologically relevant implant materials and technologies for fabrication of scaffolds. There have been tremendous advancements with respect to scaffold synthesis. The earlier researches had focused on replicating the 3D structure of the defect site, where as the recent researchers are capable of performing *in situ* fabrication of the implant. Moreover, further improvements in our know-how have enabled development of live grafts by utilizing stem cells for the purpose.

In the following sections the authors have attempted to summarize the need for addressing bone tissue engineering with special emphasis on craniomaxillofacial regeneration. However, the approach was not diluted and the focus was maintained on discussing the advancement in technologies over the recent years that have opened up new avenues of scaffold fabrication in the field of regenerative medicine.

**Methods:** After a thorough literature survey, the authors concluded to focus this chapter about the advancements in the technologies for fabrication of bone implants. The authors formulated the basic design of the chapter and targeted their search to the specific keywords, to avoid deviation from the theme. In order to provide an exhaustive but concise overview of the recent developments in methodologies for creation of craniomaxillofacial implants, the authors used various search engines including PubMed, Scopus, Google Scholar and Web of Science. The shortlisted research articles were carefully curated on the basis of their relevance. The authors selected majority of recent articles that highlight the current advances in implant fabrication techniques. To inculcate the basic concepts of materials and techniques, some of the archaic references were also incorporated in the article. The data from these reference articles was then extracted to prepare a summary of advanced techniques of scaffold fabrication, which have gained popularity due to their efficacy and cost effectiveness.
