Page 180 - Read Online

Page 2 of 12 Nelms et al. Plast Aesthet Res 2019;6:21 I http://dx.doi.org/10.20517/2347-9264.2019.40

INTRODUCTION
A mandibular defect is the loss of a lower jaw bone segment that produces a gap within the bone of 2 cm
[1]
or more, resulting in a continuity or non-continuity mandibular defect . These defects primarily arise
[2]
from tumor resection, infection, physical trauma, and osteomyelitis . Such a critical defect will not heal
[3]
on its own or regenerate more than 10% of the lost bone within the lifetime of the patient . Not only is
mandibular bone important for craniofacial aesthetics, but also for the support of muscles of mastication,
[4]
facial expression and speech . Therefore, the choice of scaffold to repair the defect must allow for sufficient
muscle attachment to restore oral and maxillofacial function, which has been shown to have significant
impact on the patient’s quality of life . Thus, to achieve successful reconstruction, care must be taken to
[5]
[6]
restore both aesthetics and functional capacity .
The autologous fibular free flap is currently the workhorse for mandibular defect repair which, along
with other autologous free vascularized tissue transfer, is considered the “gold standard” for mandibular
reconstruction because of their osteogenic, osteoinductive, and osteoconductive properties, in combination
[7,8]
with the avoidance of an immune reaction . These grafts also contain live stem or osteoprogenitor
[9]
cells that themselves migrate, proliferate, and potentiate bone healing . The major concern with using
[10]
a fibular free flap is donor site morbidity, which has been reported to occur in 31.2% of patients . These
complications include wound-healing disturbance, paresthesias, cold intolerance, motor weakness of the
lower leg muscles, pain, edema, poor aesthetics, and gait disturbance, and has been reported to lead to long
[11]
term morbidities in 17% of patients, and severe disability in 4% of patients . To circumvent this problem,
cadaver grafts may be an attractive option, however, osteoclastic resorption, risk of disease transmission
(viral) and immune reaction make this a less than ideal alternative [12-14] . Additionally, synthetic grafts
designed from metals or polymers are not bioactive and do not bond to bone or support bone cell function,
and can also induce the formation of fibrous tissue at the interface between the implant and bone,
which can interfere with bone healing and cause bone resorption, fracture, and eventual failure of the
implant [15-17] .

If advancement is to be made beyond these methods in an effort to prevent such suffering to the patient,
the following factors seem to be important in the design of a biotechnology capable of adequately closing
a critical osseous defect: (1) a scaffold to allow bone growth on its surface (osteoconduction); (2) growth
factors that induce osteogenesis (osteoinduction); (3) cells that will support osteogenesis; and (4) vascular
supply and integration for the delivery of oxygen and nutrients to developing and native tissue [14,18] . Of
these, vascularization has been a limiting factor for the use of scaffolds in mandibular repair, since both
[19]
in vitro and in vivo construct implantation lack pre-existing vasculature . Because of these multifactorial
considerations, tissue engineering might provide the solution to this problem .
[20]

The critical focus of first-generation biomaterial design was passive biocompatibility; it was not until
second-generation biomaterials that biointeractivity for the stimulation of active tissue regeneration
emerged . Third-generation biomaterials are bioresponsive, e.g., they can activate genes to influence all
[21]
aspects of proliferation and differentiation of cells [22,23] . This assembly of scaffold material, scaffold structure
(i.e., pore size), cells and growth factors reveals the multidisciplinary nature of tissue engineering, which
[21]
is the intersection of material science, mechanical engineering, clinical medicine, and genetics . In
mandibular reconstruction, the primary goals of tissue engineering include reducing donor site morbidity,
[24]
operative time, and operative complexity . If non-vascularized flaps can be used (i.e., patients who have
not been and are not planned to undergo radiation), favorable results have been reported with the adjunct
use of tissue engineering for mandibular reconstruction [25,26] . Furthermore, modern regenerative medicine
builds on tissue engineering designs to direct the surrounding native cellular environment toward a
healing process, thereby making use of foreign biological material to recreate cells and rebuild tissues.