Cranial Bone Defects: Current and Future Strategies

Caroline Szpalski, M.D.; Jason Barr, B.A.; Meredith Wetterau, M.D.; Pierre B. Saadeh, M.D.; Stephen M. Warren, M.D.


Neurosurg Focus. 2010;29(6):e8 

In This Article

Abstract and Introduction


Bony defects in the craniomaxillofacial skeleton remain a major and challenging health concern. Surgeons have been trying for centuries to restore functionality and aesthetic appearance using autografts, allografts, and even xenografts without entirely satisfactory results. As a result, physicians, scientists, and engineers have been trying for the past few decades to develop new techniques to improve bone growth and bone healing. In this review, the authors summarize the advantages and limitations of current animal models; describe current materials used as scaffolds, cell-based, and protein-based therapies; and lastly highlight areas for future investigation. The purpose of this review is to highlight the major scaffold-, cell-, and protein-based preclinical tools that are currently being developed to repair cranial defects.


Bony defects in the craniomaxillofacial skeleton can occur as a result of congenital defects (for example, in 2001, 37,732 children underwent surgery to repair birth defects) or acquired injuries (for example, in 2001, 24,298 patients required maxillofacial surgery for injuries to the face and jaw) ( Regardless of their cause, bony defects are functionally debilitating, socially incapacitating, and biomedically and economically burdensome.

The war on terrorism has brought a myriad of new challenges to maxillofacial surgeons, plastic surgeons, and neurosurgeons: combat-associated craniomaxillofacial injuries. Wars in Iraq and Afghanistan have resulted in the greatest incidence of head trauma since the Vietnam conflict. Increased survival because of body armor and advanced battlefield medicine, as well as the increased use of explosive devices, has contributed to the increased incidence of craniomaxillofacial combat injuries. Patients once not considered amenable to reconstructive surgery are now being aggressively treated and are surviving devastating head trauma. This unique patient population ultimately requires reconstruction of the cranial skeleton for protection of the brain as well as aesthetic and functional restoration of the calvaria or the bones of the face. These patients require countless procedures and are often left with poor aesthetic and functional results.

It is now well known that successful spontaneous calvarial reossification only occurs in infants younger than 2 years of age.[27] Thus, a variety of materials and methods have been proposed to restore such defects including autogenous bone grafts and allogeneic banked bone, demineralized matrix pastes, ceramic scaffolds, and even synthetic materials and bone substitutes such as calcium ceramics. More recently, cell-based alternatives and BMPs have also been used.[26] The multitude of methods reflects both the inadequacy of each technique, as well as the pressing need to adequately reconstruct the skeleton. While each method may achieve craniofacial reconstruction, each possesses inherent limitations, such as donor-site morbidity, an obligatory graft resorption phase, contour irregularities, insufficient autogenous resources, disease transmission, graft-versus-host disease, immunosuppression, structural failure, and foreign body infection. These limitations preclude most large defects from being repaired with these materials. Therefore, the need for new and improved treatment options is urgent.

To solve these issues, scientists, physicians, and engineers are collaborating to design new tissues to repair cranial defects. Because bone formation is an intricate and dynamic process, an interdisciplinary team effort is a requirement for the generation of functional tissue. Many strategies have been employed including cell-based therapies, cellular and acellular scaffolds, recombinant gene therapy, and topical small molecule therapies among others. Although bone-tissue engineering for the treatment of cranial defects is a multistep and multicomponent process, for clarity we will separately highlight every major tool that is currently being developed to solve common craniofacial problems.


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