# Three-Dimensional Scaffolds Designed and Printed Using CAD/CAM Technology: A Systematic Review
## 1 Introduction  
It is anticipated that about two million bone grafts are performed worldwide each year [1, 2] to repair significant bone defects caused by severe trauma, tumor excision, absence of union after a fracture, infections or congenital illnesses [3].  
Autografts (microvascularized free grafts) are the gold standard for bone grafts, but due to their limited availability, high morbidity, need for intraoperative modification, and structural differences between bones, alternatives like allografts and xenografts have been developed. Allografts enable scaffolds to be generated in a wide range of forms and sizes; nevertheless, this type of graft is linked with restricted revascularization, can elicit an immunological response in the recipient patient, can transmit infections, and can induce long-term mechanical failures [2, 3, 4].  
For this reason, various possibilities have been presented, such as sintered calcium phosphates (beta-tricalcium phosphate) or hydroxyapatite, which are utilized as bone substitutes in orthopedic surgery since their properties are remarkably similar to those of organic apatite crystals from natural bone. However, these types of materials are limited to not-too-large bone defects and to the regeneration of bones that do not have to bear too much load as their biomechanical properties are poor [2, 3].  
One of the major obstacles in the creation of bone substitutes is that there is substantial anatomical heterogeneity across patients, and bone abnormalities vary based on the type of defect and the mechanism that caused it [3].  
The concept of prosthesis-guided bone reconstructive surgery is particularly important for reconstructing bone structures involved in masticatory function. This is because, at times, the mandibular bone grafts are so thin that the implants emerge too low at the level of the floor of the mouth [4].  
All of this justifies the use of additive manufacturing (AM) in conjunction with computer-aided design (CAD) for the purpose of designing scaffolding and personalized grafts for each patient based on CBCT (cone beam computed tomography), CT (computed tomography) or magnetic resonance imaging [3,4].  
The intricate design of face bone structures complicates scaffolding material research, as does the requirement to produce biocompatible, osteoinductive and osteoconductive materials with appropriate mechanical qualities. New printing methods enable the combination of biomaterials made of synthetic or natural polymers (degradable or not) or hydrogels [4].  
Biopolymers are the most recent trend in bone scaffolding materials development. Microbial polyhydroxyalkanoate (PHAs) are thermoplastic biopolymers that accumulate in the cytoplasm of cultivated bacteria. They are regarded the most promising biopolymers because of their sustainability, biodegradability, and biocompatibility qualities [4].  
Printed dental scaffolds for bone regeneration represent a potential field of research. The materials currently being used are:  
* Hydroxyapatite-based scaffolds: these scaffolds have been discovered to be better suited for mechanically demanding bone regeneration due to their microporosity [5].
* Biphasic and triphasic scaffolds: they have been designed for the regeneration of periodontal ligaments and cement, as well as alveolar bone tissue [6].
* GelMA/PEGDA/F127 DA scaffolds: these scaffolds have proven to be beneficial in the treatment of bone deformities [7].
* Oxygen-releasing scaffolds: incorporating oxygen supply into 3D-printed scaffolds has been shown to promote bone repair in mice [8].
* Icarini-releasing scaffolds: icarini-encapsulated scaffolds have been designed to promote bone regeneration in situ [9].
* Polycaprolactone scaffolds with nanosilicates: these biomaterials customized using 3D printing technology have the ability to address the needs of oral and maxillofacial bone repair and regeneration [10].