Research progress on the biological modifications of implant materials in 3D printed intervertebral fusion cages

Anterior spine decompression and reconstruction with bone grafts and fusion is a routine spinal surgery. The intervertebral fusion cage can maintain intervertebral height and provide a bone graft window. Titanium fusion cages are the most widely used metal material in spinal clinical applications. However, there is a certain incidence of complications in clinical follow-ups, such as pseudoarticulation formation and implant displacement due to nonfusion of bone grafts in the cage. With the deepening research on metal materials, the properties of these materials have been developed from being biologically inert to having biological activity and biological functionalization, promoting adhesion, cell differentiation, and bone fusion. In addition, 3D printing, thin-film, active biological material, and 4D bioprinting technology are also being used in the biofunctionalization and intelligent advanced manufacturing processes of implant devices in the spine. This review focuses on the biofunctionalization of implant materials in 3D printed intervertebral fusion cages. The surface modifications of implant materials in metal endoscopy, material biocompatibility, and bioactive functionalizationare summarized. Furthermore, the prospects and challenges of the biofunctionalization of implant materials in spinal surgery are discussed.

Anterior Cervical Discectomy and Fusion Using Zero-P System for Treatment of Cervical Spondylosis: A Meta-Analysis

Objective. The current study aimed to explore the efficacy of Zero profile intervertebral fusion system (Zero-P) and traditional anterior plate cage system (PC) in the treatment of cervical spondylotic myelopathy (CSM). Further, the present study evaluated effects of the treatments on medical security, height of intervertebral disc, adjacent-level ossification development (ALOD), and adjacent segmentation disease (ASD) through a systematic retrospective analysis. Methods. Studies on Zero-P system and traditional anterior plate cage system for ACDF in the treatment of CSM were searched in PubMed, Web of Science, Ovid, Embase, and Cochrane Library databases. Two independent researchers screened articles, extracted data, and evaluated the quality of the articles based on the inclusion and exclusion criteria of the current study. RevMan5.3 software was used for meta-analysis following the guidelines of Cochrane collaboration network. Cervical curvature, interbody fusion rate, preoperative and postoperative disc height index (DHI), fusion cage sinking rate, postoperative dysphagia, ASD, ALOD, and loosening of screw were compared between the two groups. Results. A total of 17 literatures were included in the present study, including 6 randomized controlled trials and 11 observational studies. The studies comprised a total of 1204 patients with CSM, including 605 patients in the Zero-P system group (Zero-P group) and 599 patients in the traditional animal plate cage group (PC group). Results of this meta-analysis showed that postoperative dysphagia [OR = 0.40, CI (0.28, 95% 0.58), P < 0.00001], ALOD [OR = 0.09, CI (0.02, 95% 0.39), P = 0.001], ASD [OR = 0.42, CI (0.20, 95% 0.86), P = 0.02], and screw loosening [OR = 0.20, CI (0.08, 95% 0.52), P = 0.0009] of the Zero-P group were significantly lower compared with the PC group. On the other hand, preoperative cervical curvature [WMD = −0.23, CI (−1.38, 95% 0.92), P = 0.69], postoperative cervical curvature [WMD = −0.38, CI (−1.77, 95% 1.01), P = 0.59], cage sinking rate [OR = 1.41, CI [0.52, 95% 3.82], P = 0.50], intervertebral fusion rate [OR = 0.76, CI (0.27, 95% 2.48), P = 0.38], preoperative DHI [WMD = −0.04, CI (−0.14, 95% 0.22), P = 0.65], and postoperative DHI [WMD = 0.06, CI (−0.22, 95% 0.34), P = 0.675] were not significantly different between the two groups. Conclusion. It was evident that the Zero-P system used in ACDF is superior compared with the traditional anterior plate cage system in postoperative dysphagia, avoiding ALOD, ASD, and screw loosening.

Effects of rhBMP-2 Loaded Hydroxyapatite Granules/beta-Tricalcium Phosphate Hydrogel (HA/β-TCP hydrogel) Composite on a Rat Model of Coccygeal Intervertebral Fusion.

The effects and inflammation-related side effects of bone morphogenetic protein (BMP)-2 on posterior lumbar interbody fusion are controversial. One of the potential causes for the inconsistent results is the uncontrolled release of BMP-2 from the collagen carrier. Therefore, BMP delivery systems which support effective bone regeneration while attenuating side effects are strongly sought for. We developed NOVOSIS putty (NP), a novel composite material of hydroxyapatite (HA), beta-tricalcium phosphate (β-TCP)-hydrogel, and BMP-2, which can sustainably release BMP-2 over two weeks. This study investigated the effects and side effects of NP compared with those of collagen sponge (CS) containing BMP-2 using a rat coccygeal intervertebral fusion model. The fusion rates of NP with low and high doses of BMP-2 were significantly higher than those of an iliac bone (IB) graft, but those of CS with low and high doses of BMP-2 were not different from those of the IB graft. Furthermore, the incidences of ectopic bone formation and soft tissue swelling were significantly lower in the NP group than in the CS group. The HA/β-TCP hydrogel carrier enabled superior bone induction with low-dose BMP-2 and decreased the incidence of side effects caused by high-dose BMP-2 compared with that of the collagen carrier.

Is Removal of the Internal Fixation After Successful Intervertebral Fusion Necessary? A Case–control Study Based on Patient-reported Quality of Life

BackgroundIntervertebral fusion and internal fixation are often applied to patients with lumbar spinal disease. Whether to remove the internal fixation after successful fusion remains uncertain, but such a question needs to be explored in light of concerns regarding patients’ quality of life and health insurance. We sought to probe if the removal of internal fixation after successful lumbar intervertebral fusion affects patients’ quality of life.MethodsThis was a real-world retrospective case–control study. Data of 102 patients who had undergone posterior lumbar fusion with cage and internal fixation to treat lumbar degenerative diseases were extracted from a single center from 2012 to 2020. Fifty-one patients had undergone internal fixation removal surgery, and 51 controls who retained internal fixations were matched according to demographic and medical characteristics. The quality of life of patients based on the Medical Outcomes Study Short Form 36 (SF-36) scale and their self-assessment were surveyed.ResultsThere was no statistical difference in the overall score of the SF-36 questionnaire between the two groups, but the general health (GH) subscore was lower in the case group than in the control group (P = 0.0284). Among those patients who underwent internal fixation removal, the quality of life was improved after instrument removal as indicated by an increased overall score (P = 0.0040), physical functioning (PF) (P = 0.0045), and bodily pain (BP) (P = 0.0008). Among patients with pre-surgery discomfort, instrument removal generated better outcomes in 25% and poor outcomes in 4.2%. Among patients without pre-surgery discomfort, instrument removal generated better outcomes in 7.4% and poor outcomes in 11.1%.ConclusionAmong patients who achieved successful posterior lumbar internal fixation, whether or not to remove the fixation instruments should be evaluated carefully. In patients experiencing discomfort, instrument removal could improve their quality of life, but the benefits and risks should be comprehensively explained to these patients. Instrument removal should not be routinely performed due to its limited or even negative effect in patients who do not report discomfort before surgery.

Low-frequency electromagnetic fields combined with tissue engineering techniques accelerate intervertebral fusion

Background Intervertebral fusion is the most common surgery to treat lumbar degenerative disease (LDD). And the graft material used in the operation is derived from the iliac crest to promote fusion. However, autografts possess the fatal disadvantage of lack of source. Therefore, economical and practical bone substitutes are urgently needed to be developed. Sinusoidal electromagnetic fields (EMF) combined with tissue engineering techniques may be an appropriate way to promote intervertebral fusion. Methods In this research, porous scaffolds made of polycaprolactone (PCL) and nano-hydroxyapatite (nHA) were used as cell carriers. Then, the scaffolds loaded with bone marrow mesenchymal stem cells (BMSCs) were treated with sinusoidal electromagnetic field and the osteogenic capability of BMSCs was tested later. In addition, an intervertebral disc of the tail vertebra of the rat was removed to construct a spinal intervertebral fusion model with a cell-scaffold implanted. The intervertebral fusion was observed and analyzed by X-ray, micro-CT, and histological methods. Results BMSCs stimulated by EMF possess splendid osteogenic capability under an osteogenic medium (OM) in vitro. And the conditioned medium of BMSCs treated with EMF can further promote osteogenic differentiation of the primitive BMSCs. Mechanistically, EMF regulates BMSCs via BMP/Smad and mitogen-activated protein kinase (MAPK)-associated p38 signaling pathways. In vivo experiments revealed that the scaffold loaded with BMSCs stimulated by EMF accelerated intervertebral fusion successfully. Conclusion In summary, EMF accelerated intervertebral fusion by improving the osteogenic capacity of BMSCs seeded on scaffolds and might boost the paracrine function of BMSCs to promote osteogenic differentiation of the homing BMSCs at the injured site. EMF combined with tissue engineering techniques may become a new clinical treatment for LDD.

Additive-manufactured Ti-6Al-4 V/Polyetheretherketone composite porous cage for Interbody fusion: bone growth and biocompatibility evaluation in a porcine model

Background We developed a porous Ti alloy/PEEK composite interbody cage by utilizing the advantages of polyetheretherketone (PEEK) and titanium alloy (Ti alloy) in combination with additive manufacturing technology. Methods Porous Ti alloy/PEEK composite cages were manufactured using various controlled porosities. Anterior intervertebral lumbar fusion and posterior augmentation were performed at three vertebral levels on 20 female pigs. Each level was randomly implanted with one of the five cages that were tested: a commercialized pure PEEK cage, a Ti alloy/PEEK composite cage with nonporous Ti alloy endplates, and three composite cages with porosities of 40, 60, and 80%, respectively. Micro-computed tomography (CT), backscattered-electron SEM (BSE-SEM), and histological analyses were performed. Results Micro-CT and histological analyses revealed improved bone growth in high-porosity groups. Micro-CT and BSE-SEM demonstrated that structures with high porosities, especially 60 and 80%, facilitated more bone formation inside the implant but not outside the implant. Histological analysis also showed that bone formation was higher in Ti alloy groups than in the PEEK group. Conclusion The composite cage presents the biological advantages of Ti alloy porous endplates and the mechanical and radiographic advantages of the PEEK central core, which makes it suitable for use as a single implant for intervertebral fusion.

Additive-Manufactured Ti-6Al-4V/Polyetheretherketone Composite Porous Cage for Interbody Fusion: Bone Growth and Biocompatibility Evaluation in a Porcine Model

Background: We developed a porous Ti alloy/PEEK composite interbody cage by utilizing the advantages of polyetheretherketone (PEEK) and titanium alloy (Ti alloy) in combination with additive manufacturing technology. Methods: Porous Ti alloy/PEEK composite cages were manufactured using various controlled porosities. Anterior intervertebral lumbar fusion and posterior augmentation were performed at three vertebral levels on 20 female pigs. Each level was randomly implanted with one of the five cages that were tested: a commercialized pure PEEK cage, a Ti alloy/PEEK composite cage with nonporous Ti alloy endplates, and three composite cages with porosities of 40%, 60%, and 80%, respectively. Micro-computed tomography (CT), backscattered-electron SEM (BSE-SEM), and histological analyses were performed. Results: Micro-CT and histological analyses revealed improved bone growth in high-porosity groups. Micro-CT and BSE-SEM demonstrated that structures with high porosities, especially 60% and 80%, facilitated more bone formation inside the implant but not outside the implant. Histological analysis also showed that bone formation was higher in Ti alloy groups than in the PEEK group. Conclusion: The composite cage presents the biological advantages of Ti alloy porous endplates and the mechanical and radiographic advantages of the PEEK central core, which makes it suitable for use as a single implant for intervertebral fusion.