###### Abstract  
The ideal biomaterials substitute for bone repair should possess the following characteristics: provide osteogenic, osteoinductive and osteeconductive properties; stimulate the neo-angiogenesis process; absence of antigenic, teratogenic or carcinogenic reactions; avoid the systemic toxicity complications; assure satisfactory support and stability from mechanical properties point of view; hydrophilic nature of the surface properties and good interface with human bone; good handling in clinical condition and ability to be easy sterilized; and able to be supplied in sufficient quantities with reduced costs. Despite years of effort, the perfect bone reconstruction material has not yet been developed; further effort is required to make this objective feasible. The aim of this article is to provide a contemporary and comprehensive overview of the grafting materials that can be applied for the treatment of bone defects by the clinicians from orthopedics surgery, neurosurgery and dentistry, discussing their properties, advantages and disadvantages, and illuminating present and future perspectives in the field of bone graft and biomaterials substitutes for bone repair, from clinical needs to advanced biomaterials research.  
bone; grafting; advanced biomaterials; bioc Composites; nanostructures; in-vivo; in-vitro; laser cutting +
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Direct bone healing can occur only when anatomical reduction of the bone fragments and their rigid fixation is achieved, which means a minimal interfragmentary movement. Bone healing in this case is conducted in a special way, i.e., by contact or gap healing.  
Indirect healing is most common in the natural evolution of fractures; it does not require anatomical reduction of the fracture or special stability of the fixation; moreover, the healing speed through this mechanism is improved by micromovements and especially by direct axial loading.  
If this process is disturbed by different mechanical or biological issues, the evolution is towards a delay in consolidation or pseudoamthrosis, situations with a profound negative effect on the functionality of the affected bone segment, as well as on the limb of which it is a part [1]. Understanding this mechanism is crucial in taking the best therapeutic decisions in aid of healing as quickly as possible and without sequelae.  
Pseudarthrosis is defined as failure to achieve bone healing 9 months after trauma, or lack of clinical and radiological signs of healing progression for 3 months [2]. Other authors consider 6 months after trauma the time of the onset of pseudarthrosis. For this condition, bone grafts, bone substitutes and bioactive factors can enhance the healing process [3].  
They are many other pathologic conditions that requires the use of bone grafts or substitutes with or without bioactive factors: open fractures with loss of bone substance; revision arthroplasties with important reduction of local bone capital after prosthetic component loosening; surgical treatment of infections and tumors by resections [4]; and arthroresis (joint fusion). Filling the spaces created for the purpose of bone axis restoration (osteotomies) is another potential indication for bone grafts.  
Bone defects can be segmental or cavitary. For segmental defects, the bone graft must be structured in order to ensure the primary mechanical strength of the replaced segment. In cavitary defects, the graft needs only to fill the cavity, without offering mechanical strength. The morselized, cancellous graft, without any mechanical strength, is much faster integrated than the structured one due to its large trabecular surface area which promotes revascularization and incorporation at the recipient site.