Reconstruction of the orbital defects commenced in the 1950s, and Converse applied the bone transplantation to repair a blowout fracture of the orbit.
7 Since then extensive research has been carried out on material and surgical procedures.
4 –6 There have been recent advances in surgical procedures, including reconstruction of orbital structures and recovery of the function and reposition of the eyeball by transplantation of bone or artificial material.
8 –10 Nevertheless, along with improving surgical procedures, the nature and usage of implants are also crucial. Bone transplantation, including autogenous, allogenous, and xenogeneic transplantation, is a vital method for the repair of orbital defects and the recovery from damage. Ilium spongy bone is usually applied in autogenous transplantation because of its good transduction, osteoinduction, and osteogenesis, and it is acknowledged to be the gold standard for the clinical bone repair treatment.
1 Because the supply of autogenous bone is limited, it cannot satisfy large volume defects, and it may also lead to the risk of bleeding, infection, or chronic pain.
2 Although allogenous bones have a wide source and show good transduction, they does not allow for osteoinduction and osteogenesis and present a potential risk of human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infection and immunologic rejection.
3 Xenogeneic implants, derived from animals, provide an abundant source but must undergo various methods to eliminate foreign antigens, after which the risk of rejection may still exist. The spread of animal-derived diseases and ethical issues must also be considered with xenogeneic transplantation.
11
The use of artificial materials in transplantation has been a hot topic in recent decades, because of their wide availability, plasticity, and safe convenient usage. There are several kinds of materials that have been applied in orbital repair, including polymeric porous polyethylene, hydroxyapatite, and titanium. Polyethylene is nonvisualizable and therefore does not allow for postoperative examination. Hydroxyapatite is fragile and not able to be shaped. The mechanical properties of titanium vary remarkably from human bones, and titanium is unable to undergo vascularization. Moreover, all these materials are either nondegradable or hard to degrade. Hence, they exist as a foreign body, potentially leading to rejection, infection, cyst formation, or implant displacement.
4 –6 Consequently, biodegradable, osteogeneic, and osteoinductive artificial orbit material is in high demand. Researchers have tested several materials for orbital repair, including L-lactic acid, poly-L/DL-lactic acid, and polyglycollic acid. The degradation of these materials was uncontrollable, and they may release acidic substances to activate inflammation.
12 Moreover, the interior of these materials is cell free, so osteogenesis is attributed to host bone cells, which delays healing after implantation. To date, no ideal material has been identified for clinical orbit bone repair. Since the 1990s, the rapid development of tissue-engineering techniques and the increased interdiscipline collaboration between the fields of molecular biology, cell biology, and material science have realized bone construction via tissue engineering and now direct research on bone replacement materials.
13
Tissue-engineering research is currently focused on osteology and oral surgery, and animal experiments have proven the feasibility of mandible, cranium, and limb repair via tissue engineering.
14 –16 However, little has been reported on the application of these technologies in the repair of orbit bone. Rohner et al.
17 investigated the repair of swine orbital walls with porous polycaprolactone scaffold/fresh autogenous bone marrow complexes. Active osteogenensis was observed in this experiment, and bone formation was higher than that in the control of material only.
17 This study indicated that bone marrow will promote orbital repair. However, the quantity of BMSCs in fresh bone marrow is low, approximately 1/10
6 of the total cells. Hence isolation and purification of BMSCs, followed by in vitro cultivation, are necessary. The methods for culture and osteogenic-induction of BMSCs in vitro have been improved and applied to large animal bone defect repair.
18,19 However, there are distinctions between the anatomic structure of mandibles and limbs and that of the orbital, and therefore further work is required to optimize tissue engineering for the orbital specifically.
In the present study, we created a 25-mm–long segment defect in the inferior orbital rim, with irregular arch, to allow for our investigations into the formation and rebuilding of new bone in the repair of irregular and non–weight-bearing bone. A prefabricated β-TCP scaffold was combined with autogenous BMSCs cultured in vitro. This complex was then applied to the repair of the suborbital defect. The feasibility of repair orbital rim via tissue engineering was explored, and preliminary data for clinic application have been obtained.
The construction of the complex is vital for tissue-engineering repair of the orbit, including the seed cells and the scaffold materials. In this study, BMSCs were adopted as the seed cells and β-TCP was used as the scaffold; the complex was combined and cultured in vitro. Our results indicate that BMSCs possess good regeneration and differentiation ability, in agreement with a previous report.
20,21 The orbital rim is a nonburden bone, so there were no strict requirements on the intensity of the material. By increasing aperture and porosity, bone repair and vascularization could be facilitated. The average diameter of the pores in the β-TCP scaffold was 406.3 μm, and the porosity was 84.63% in this study, which satisfy the requirements of tissue engineering.
22,23 The compressive strength was >2 MPa, meeting the standard for spongy bone; hence the material would fulfill the requirements for defect repair.
In this study, the induced BMSC/β-TCP complex was implanted onto the defect in the inferior orbital rim. The results demonstrated that the scaffold was degrading and new bone was being produced gradually, and the induced BMSC/β-TCP complex showed good shape and bony conjugation, with the majority of the complex being replaced by new bone tissue 3 months postoperatively. In contrast, almost no new bone formation and nonunion were observed in the TCP alone group. These results indicated that induced BMSCs promoted the regeneration and reconstruction of orbital bone in the treatment of larger bone defects. Petite et al.
24 used noninduced BMSC complexes to repair defects in goat metatarsal bone, revealing that noninduced BMSCs possess certain osteogenic abilities. Therefore, we tested noninduced BMSC/β-TCP complexes in the treatment of defects in the orbital rim. The results showed incomplete bony repair or nonunion, and the bone density was lower than that of the normal control 3 months postoperatively. In conclusion, our findings indicate that the osteogenic ability of noninduced BMSCs is weak and that osteogenic induction is necessary for seed cells during the repair of larger bone defects.
The orbit is located in the central part of the face and is involved in the formation of the facial outline and, in particular, protection of the eyes. Hence, extreme effort should be invested in recovery of the original anatomic form when repairing bony defects of the orbit. In the case of complex orbit fracture, defects of the adjacent facial bones, such as the skull, zygoma, and nasal bone, may also need to be repaired, so a prefabricated scaffold is vital in the treatment. For this reason, we applied computer-aided design and computer-aided manufacturing (CAD/CAM) to the analysis of the canine inferior orbital and prepared a scaffold to match the defect in shape, and this resulted in good repair. One-week postoperative CT examination revealed that the inferior orbital rim of each group showed good repair, indicating that the β-TCP scaffold made via CAD/CAM fit the defects well. This method enhanced the precision and convenience of surgery and confirmed the tight joining of the implants and the broken margin of the orbital rim. The 12-week follow-up examination demonstrated that the scaffolds maintained their initial shape along with degradation of the material and new bone replacement after implantation in the induced complex group. Thus, it was shown that 3D prefabricated materials facilitated treatment and ensured proper shape recovery.
Wolff
25 proposed that bone in a healthy person or animal will adapt to the loads it is placed under. If the loading on a particular bone increases, the bone will remodel itself over time to become stronger to resist that sort of loading. The internal architecture of the trabeculae undergoes adaptive changes, followed by secondary changes to the external cortical portion of the bone. The converse is true as well: If the loading on a bone decreases, the bone will become weaker because of turnover, and it is less metabolically costly to maintain. There is no stimulus for continued remodeling required to maintain bone mass. Therefore, when repairing the non–weight-bearing inferior orbital rim, it is necessary to determine whether the bone regenesis will match the material degradation, and whether the implants will rebuild approaching the physiological function and appearance. Our present study revealed that the induced BMSC/β-TCP group repaired the inferior orbital rim well, showing physiological appearance, building bony conjugation between the material and the broken end of orbital rim, and remodeling the fibrous bone to the lamellar bone. Taken together, these data indicate that repair and rebuilding can be achieved at the inferior orbital rim via tissue engineering. Application of CAD/CAM in the manufacture of the scaffold forms the basis of repair, and the BMSCs promote the regenesis of bone. Subsequent remodeling and shaping of the new bone induced by the effects of the orbit microenvironment, such as muscle shrinkage or biological mechanics, lead to the recovery of physiological appearance and function. The precise mechanisms involved in this proc need to be elucidated. In addition, further follow-up studies are required to assess the long-term effects of the tissue-engineering method in orbital repair.
In summary, the tissue-engineered bones from osteogenically induced BMSCs and 3D biodegradable β-TCP can efficiently repair the orbital defects in canines. This pilot study proves the feasibility of repair of irregular and non–weight-bearing orbital bones in a tissue-engineered manner and provides experimental results for clinical research.
Supported by the Shanghai Leading Academic Discipline Project (S30205), the National Natural Science Foundation of China (30973279 and 81000404), the National Key Program for Basic Research of China (2010CB529902), the Doctoral Fund of Ministry of Education of China (BXJ0826), and the Science and Technology Commission of Shanghai (08ZR1412900 and 10411964000).
The authors thank Ji-Fan Hu from Stanford University Medical School for his helpful comments on the manuscript; and Ji-Fan Hu and International Science Editing Compuscript Ltd. for reviewing the revised manuscript before submission.