Due to matching biomechanical properties and significant biological activity, Mg-based implants present great potential in orthopedic applications. In recent years, the biocompatibility and therapeutic effect of magnesium-based implants have been widely investigated in trauma repair. In contrast, the R&D work of Mg-based implants in spinal fusion is still limited. This review firstly introduced the general background for Mg-based implants. Secondly, the mechanical properties and degradation behaviors of Mg and its traditional and novel alloys were reviewed. Then, different surface modification techniques of Mg-based implants were described. Thirdly, this review comprehensively summarized the biological pathways of Mg degradation to promote bone formation in neuro-musculoskeletal circuit, angiogenesis with H-type vessel formation, osteogenesis with osteoblasts activation and chondrocyte ossification as an integrated system. Fourthly, this review followed the translation process of Mg-based implants via updating the preclinical studies in fracture fixation, sports trauma repair and reconstruction, and bone distraction for large bone defect. Furthermore, the pilot clinical studies were involved to demonstrate the reliable clinical safety and satisfactory bioactive effects of Mg-based implants in bone formation. Finally, this review introduced the background of spine fusion surgeryand the challenges of biological matching cage development. At last, this review prospected the translation potential of a hybrid Mg-PEEK spine fusion cage design.

With the advances in biological technologies over the past 20 years, a number of new therapies to promote bone healing have been introduced. Particularly in the spinal surgery field, more unprecedented biological therapeutics become available to enhance spinal fusion success rate along with advanced instrumentation approaches. Yet surgeons may not have been well informed about their safety and efficacy profiles in order to improve clinical practices. Therefore there is a need to summarize the evidence and bring the latest progress to surgeons for better clinical services for patients. We comprehensively reviewed the literatures in regard to the biological therapeutics for enhancement of spinal fusion published in the last two decades. Autograft bone is still the gold standard for bone grafting in spinal fusion surgery due to its good osteoconductive, osteoinductive, and osteogenic abilities. Accumulating evidence suggests that adding rhBMPs in combination with autograft effectively promotes the fusion rate and improves surgical outcomes. However, the stimulating effect on spinal fusion of other growth factors, including PDGF, VEGF, TGF-beta, and FGF, is not convincing, while Nell-1 and activin A exhibited preliminary efficacy. In terms of systemic therapeutic approaches, the osteoporosis drug Teriparatide has played a positive role in promoting bone healing after spinal surgery, while new medications such as denosumab and sclerostin antibodies still need further validation. Currently, other treatment, such as controlled-release formulations and carriers, are being studied for better releasing profile and the administration convenience of the active ingredients. As the world's population continues to grow older, the number of spinal fusion cases grows substantially due to increased surgical needs for spinal degenerative disease (SDD). Critical advancements in biological therapeutics that promote spinal fusion have brought better clinical outcomes to patients lately. With the accumulation of higher-level evidence, the safety and efficacy of present and emerging products are becoming more evident. These emerging therapeutics will shift the landscape of perioperative therapy for the enhancement of spinal fusion.

Objective: This study aimed to describe the changes in spinopelvic sagittal alignment in the sitting position after posterior lumbar fusion, and to identify the factors influencing unfused adjacent segment lordosis. Methods: Consecutive patients with lumbar degenerative disease who underwent posterior lumbar interbody fusion between December 2010 and April 2012 were recruited. Lateral full spine radiographs were obtained in the standing, erect sitting, and natural sitting positions. Spinopelvic parameters were measured preoperatively and at the final follow-up. Results: The data of 63 patients were analyzed in this study. The average age was 61.6 ± 11.0 years. When changing from standing to sitting at the final follow-up, all spinopelvic sagittal parameters with the exceptions of pelvic incidence and thoracic kyphosis were significantly altered. The most noticeable changes occurred in the natural sitting position, with the spine slumped toward achieving a C-shaped sagittal profile. Multiple linear regression analysis revealed that when changing to a natural sitting position, age and fusion levels reflected the changes in lumbar lordosis (ΔLL), age and lumbosacral fusion reflected the changes in upper residual lordosis (ΔURL). Conclusion: The most noticeable changes in spinopelvic sagittal alignment occurred in the natural sitting position after lumbar fusion. Age, fusion levels, and lumbosacral fusion significantly influenced the differences in LL and URL between the standing and natural sitting position. These characteristics should be fully considered when planning spinal realignment surgery and investigating the etiological factors of junctional complications.

The clinical outcome of spinal fusion surgery is closely related to the success of bone fusion. Nowadays, the interbody cage which is used to replace the disc for spinal fusion is expected to have biological activity to improve osseointegration, especially for the aging and osteoporotic patients. Here, through micro-arc oxidation and hydrothermal treatment (MAO + HT), a bioactive CaP coating with micro/nano multilevel morphology was developed on 3D printed Ti6Al4V alloy then verified in vitro and in sheep anterior cervical decompression fusion model systematically. In vitro studies have confirmed the positive effects of characteristic micro/nano morphology and hydrophilicity of the coating formed after surface treatment on the adhesion, proliferation, and osteogenic differentiation of osteoblast precursor cells. Furthermore, the MAO + HT treated interbody cage showed a closer integration with the surrounding bone tissue, improved kinetic stability of the implanted segment, and significantly reduced incidence of fusion failure during the early postoperative period, which indicated that such a surface modification strategy is applicable to the biomechanical and biological microenvironment of the intervertebral space.

Despite the many studies carried out over the past decade to determine the biodegradation performance of magnesium and its alloys, few studies focused on the effect of altered surface area to volume ratio on in vitro and in vivo degradation rate and osteogenesis. Here, high purity magnesium cylindrical rods with gradient of surface area to volume ratio were processed by excavating different numbers of grooves on the side surface. The immersion test in SBF solution and the rat femoral condylar bone defect model were used to evaluate the degradation of magnesium rods in vitro and in vivo, respectively. We demonstrated that, the increased number of grooves on the HP magnesium surface represented a decrease in the percentage of residual volume over time, not necessarily an increase in absolute degradation volume or a regular change in corrosion rate. Furthermore, there were strong linear correlations between the relative degradation volume and the initial surface-to-volume ratio of HP magnesium rods both in vitro and in vivo. The difference in the slope of this relationship in vitro and in vivo might help to determine the possible range of in vivo degradation rates via in vitro data. In addition, the corrosion rate is more suitable for evaluating bone formation surrounding the different HP magnesium rods. Our findings in this work may facilitate adjusting the in vivo degradation and osteogenesis of different kinds of orthopedic implants made of the same magnesium-based material, and thus, accelerate the clinical popularization and application.

Endplate osteochondritis is considered one of the major causes of intervertebral disc degeneration (IVDD) and low back pain. Menopausal women have a higher rate of endplate cartilage degeneration than similarly aged men, but the related mechanisms are still unclear. Subchondral bone changes, mainly mediated by osteoblasts and osteoclasts, are considered an important reason for the degeneration of cartilage. This work explored the role of osteoclasts in endplate cartilage degeneration, as well as its underlying mechanisms. A rat ovariectomy (OVX) model was used to induce estrogen deficiency. Our experiments indicated that OVX significantly promoted osteoclastogenesis and anabolism and catabolism changes in endplate chondrocytes. OVX osteoclasts cause an imbalance between anabolism and catabolism in endplate chondrocytes, as shown by a decrease in anabolic markers such as Aggrecan and Collagen II, and an increase in catabolic markers such as a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) and matrix metalloproteinases (MMP13). Osteoclasts were also confirmed in this study to be able to secrete HtrA serine peptidase 1 (HTRA1), which resulted in increased catabolism in endplate chondrocytes through the NF-κB pathway under estrogen deficiency. This study demonstrated the involvement and mechanism of osteoclasts in the anabolism and catabolism changes of endplate cartilage under estrogen deficiency, and proposed a new strategy for the treatment of endplate osteochondritis and IVDD by targeting HTRA1.