The ideal bioabsorbable materials for cage devices should possess three properties: the capability of degradation during a distinct period, the property not to obscure postoperative radiological estimation of intervertebral fusion, and the stiffness comparable with that of bone. During the degradation process, loading is transferred gradually to the newly formed bone and the cage is replaced with bone. Several previous studies involved animal experiments or clinical trials with bioabsorbable cages [9–16]. Most of these bioabsorbable cages were composed of polylactic acid [9–11, 15], which naturally degrades to carbon dioxide and water. Other bioabsorbable substances are polymer–calcium phosphate composites, composites of polyglycolic acid, multiamino acid copolymer/nanohydroxyapatite/calcium sulfate, and multiamino acid copolymer/α-tricalcium phosphate [17–19]. Although most of these studies demonstrated successful fusion with these cages, some adverse events were reported. Kandziora et al. [4] showed that poly-L-lactide-co-D, L-lactide (PLDLLA) cages were associated with osteolysis in a sheep model at 12 weeks after the operation. They found a severe foreign body reaction causing osteolysis around the PLDLLA cage. The osteolysis caused skepticism about the value of PLDLLA as an implant.
MPC has attracted much attention as a potential biodegradable bone implant material. The main components of MPC are magnesium oxide (MgO) and acid ammonium phosphates, particularly ammonium dihydrogen phosphate (NH4H2PO4). MPC powders react in the presence of water to form HN4MgPO4·6H2O (struvite) as the final product [2]. Yu et al. [20] assessed the toxicology and biocompatibility of MPC through the UDS test, Ames test, and micronuclei test and also evaluated degradation and osteogenesis in a rabbit femur condyle defect model. The results showed that MPC did not induce DNA damage or gene mutations. As regards the implantation test, the MPC implant formed direct bonds with the host bone and exhibited good degradation at 6 months after surgery. Our previous studies on a pure MPC cage also showed intervertebral fusion and conspicuous degradation of MPC at 6 months after implantation in a porcine lumbar spine interbody fusion model. However, the major drawback of the pure MPC cage as an implant is its high brittleness, prompting further modification to increase the toughness.
Magnesium is the fourth most abundant cation in the human body, with approximately half of the total physiological magnesium stored in bone tissue [3]. The elastic modulus and compressive yield strength of magnesium are closer to those of natural bone, while the fracture toughness of magnesium is greater than that of ceramic biomaterials such as hydroxyapatite [3]. In addition, magnesium exerts stimulatory effects on the growth of new bone tissue [21, 22]. The major drawback of magnesium as an implant is the quick corrosion in the high chloride environment at physiological pH (7.4–7.6), losing mechanical integrity before the tissue has sufficiently healed. Moreover, magnesium produces hydrogen gas in the corrosion process that is not likely to be dealt with by the host tissue immediately [21]. Daentzer et al. [23] investigated a bioabsorbable cage consisting of magnesium and polymer (poly-ε-caprolactone, PCL) in an ovine cervical model. The postoperative lateral radiographs showed gas accumulation in front of the disc space in 50% of the sheep. The gas completely disappeared within the next 3 weeks. In this study, no gas accumulation was observed at 6, 12, and 24 weeks after the operation, because the amount of magnesium in the hybrid cage was small, so hydrogen gas could easily be dealt with by the host tissue.
To our knowledge, this study is the first attempt to use MPC and magnesium as an interbody fusion cage to assist intervertebral fusion in vivo. The magnesium was employed to compensate for the lack of toughness in the MPC cage. Compared to a pure MPC cage, the hybrid Mg−MPC cage could be easily placed into the intervertebral space without fragmentation during the operation.
Cages should retain interbody distraction and resist against subsidence into the adjacent vertebra to guarantee bony fusion of a desired quality. The distractive properties of cages have been investigated in some experiments. Kandziora et al. [4] showed that a PLDLLA cage and autologous tricortical iliac crest bone graft developed a remarkable loss of DSH during an observation period of 12 weeks in a sheep cervical spine fusion model due to degradation of the implant and gradual graft collapse, respectively. Jiya et al. [16] assessed clinical and radiologic outcomes of the PLDLLA cage compared with the PEEK cage, demonstrating the PEEK cage group had a lower subsidence rate. Our study demonstrated both PEEK cages and Mg–MPC cages were able to distract intervertebral disc spaces beyond their baseline measure at 6 weeks after the operation. However, the average DSH decreased significantly in both groups at 12 and 24 weeks after the operation. Too rigorous preparation of the endplates might leave a mechanically weaker spongious bone bed to cages, thus promoting subsidence in both groups. Moreover, the decrease in DSH in the Mg–MPC group resulted partly from degradation.
Assessment of fusion was frequently based on radiographs or histology. Toth et al. [24] introduced a fusion scoring system by using high resolution radiographs. Zdeblick et al. [6] devised a grading scale to analyze the histologic fusion results. The two methods have been widely applied to analyze fusion rates in animal experiments [4, 19]. Micro-CT is more conducive to estimate the trabecular structure of newly formed bone. In this study, at 24 weeks in spite of the assistance of autologous transverse process bone grafts in the PEEK group, the Micro-CT scans revealed an equal fusion rate in both groups. Moreover, the newly formed bone tissue at the implant–vertebra interface in the Mg-MPC group seemly denser than that in the PEEK group probably due to the stimulatory effect of Mg on bone growth.
Compared to Mg–MPC group, the PEEK group showed higher stiffness in the flexion, extension, and lateral bending directions at 6 weeks after the operation. In addition to the large amount of fibrous tissue that is likely to increase the spinal stiffness, the autograft bone in the central hole of the PEEK cages may lead to quicker bone growth, improving the stability at the early stages. Other studies also revealed using bone graft was likely to affect the interbody fusion [25]. Li et al. [19] observed that titanium cages packed with autologous iliac crest bone grafts in the central hole could achieve quicker fusion than polycaprolactone-tricalcium phosphate (PCL-TCP) cages without a central hole. With the knowledge gained from these results, further research is recommended to investigate if adding a central hole in the Mg–MPC cage, which could be filled with bone grafts, can help achieve quicker fusion as well as better stability.
The histological study revealed that both the Mg–MPC cage and the PEEK cage did not behave well in terms of osseointegration, that is, empty spaces were observed at the implant–vertebra interface or around the implant due to relatively rapid degradation of the Mg–MPC cage, while the PEEK cages were surrounded by large amounts of fibrous tissue which may be a result of a foreign body reaction. The rapid degradation seems to be another possible cause of the insufficient stability at the early stage in the Mg–MPC group. The degradation rate of the bioabsorbable implants is related to the material composition, the structure, and the degradation environment [26]. Therefore, the degradation of the Mg−MPC cage could be improved by modification of the material composition or the structure of the implant.
The limitations of this study include the limited numbers of animals enrolled in each group and the time points chosen for evaluation. The follow-up period does not allow for a description of the performance of Mg–MPC cages in the long term. In addition, due to different designs of the two kinds of cages, whether the bone grafts were used, and the degradation of the Mg–MPC cages, we couldn’t take an appropriate approach to make a quantitative analysis of the tissue type, particularly the newly formed bone tissue between the two groups. Moreover, in order to create enough space to accommodate the cages, the endplates were prepared too large in the two groups, which could induce interference in the evaluation of the distractive properties of the two kinds of cages.