A novel EP4 selective agonist (KMN-159) was developed [1] and has been proven that it can act as an osteopromotive factor to repair critical-size femoral bone defects in rats at a dose-dependent manner [2]. Based on its osteopromotive properties, we hypothesized that KMN-159 could also aid in bone formation for spinal fusion. Therefore, the aim of this study was to investigate its spinal fusion effect in a dorsolateral spinal fusion model in rats. This study was performed on 192, 10-week-old male Wistar rats. The rats were randomized into 8 groups (n = 12 per group): 1) SHAM (negative control), 2) MCM (scaffold only), 3) MCM + 20 µg BMP-2 (positive control), 4-8) MCM + 0.2, 2, 20, 200 or 2000 µg KMN-159. A posterolateral intertransverse process spinal fusion at L4 to L5 was performed bilaterally by implanting group dependent scaffolds (see above) or left empty in the SHAM group (protocol no. 25-5131/474/38). Animals were euthanized after 3 weeks and 6 weeks for µCT and biomechanical testing analysis. The results showed that KMN-159 promoted new bone formation in a dose-dependent manner at 3 weeks and 6 weeks as verified by µCT. The biomechanical testing showed that the dose of 20, 200 and 2000 µg KMN-159 groups obtained comparable strength with BMP-2 group, which higher than SHAM, MCM and lower doses of 0.2 and 2 µg KMN-159 groups. In conclusion, KMN-159 could be a potential replacement of BMP-2 as a novel osteopromotive factor for spinal fusion. Acknowledgements: We are grateful to Ulrike Heide, Anna-Maria Placht (assistance with surgeries) as well as Suzanne Manthey & Annett Wenke (histology)

Although bone morphogenetic protein 2 (BMP-2) has been FDA-approved for spinal fusion for decades, its disadvantages of promoting osteoclast-based bone resorption and suboptimal carrier (absorbable collagen sponge) leading to premature release of the protein limit its clinical applications. Our recent study showed an excellent effect on bone regeneration when BMP-2 and zoledronic acid (ZA) were co-delivered based on a calcium sulphate/hydroxyapatite (CaS/HA) scaffold in a rat critical-size femoral defect model. Therefore, the aim of this study was to evaluate whether local application of BMP-2 and ZA released from a CaS/HA scaffold is favorable for spinal fusion. We hypothesized that CaS/HA mediated controlled co-delivery of rhBMP-2 and ZA could show an improved effect in spinal fusion over BMP-2 alone. 120, 8-week-old male Wistar rats (protocol no. 25-5131/474/38) were randomly divided into six groups in this study (CaS/HA, CaS/HA + BMP-2, CaS/HA + systemic ZA, CaS/HA + local ZA, CaS/HA + BMP-2 + systemic ZA, CaS/HA + BMP-2 + local ZA). A posterolateral spinal fusion at L4 to L5 was performed bilaterally by implanting group-dependent scaffolds. At 3 weeks and 6 weeks, 10 animals per group were euthanized for µCT, histological staining, or mechanical testing. µCT and histological results showed that the CaS/HA + BMP-2 + local ZA group significantly promoted bone regeneration than other treated groups. Biomechanical testing showed breaking force in CaS/HA + BMP + local ZA group was significantly higher than other groups at 6 weeks. In conclusion, the CaS/HA-based biomaterial functionalized with bioactive molecules rhBMP-2 and ZA enhanced bone formation and concomitant spinal fusion outcome. Acknowledgements: Many thanks to Ulrike Heide, Anna-Maria Placht (assistance with surgeries) as well as Suzanne Manthey & Annett Wenke (histology)

Spinal diseases such as unstable fractures, infections, primary or secondary tumors or deformities require surgical stabilization with implants. The long-term success of this treatment is only ensured by a solid bony fusion. The size of the bony defect, the often poor bone quality and metabolic diseases increase the risk of non-union and make the case a great burden for the patient and a challenge for the surgeon. The goal of spinal fusion can only be achieved if the implants used offer sufficient mechanical stability and the local biological regeneration potential is large enough to form sufficient bone. The lecture will present challenging clinical cases. In addition, implant materials and new surgical techniques are discussed. Local therapeutic effects are achieved through the release of osteopromotive or anti-resorbtive drugs, growth factors and antibiotics. By influencing biological pathways, basic orthopedic research has strong potential to further positively change future spinal surgery

Biphasic calcium phosphate (BCP) with a characteristic needle-shaped submicron surface topography (MagnetOs) has attracted much attention due to its unique bone-forming ability which is essential for repairing critical-size bone defects such as those found in the posterolateral spine. Previous in vitro and ex-vivo data performed by van Dijk LA and Yuan H demonstrated that these specific surface characteristics drive a favorable response from the innate immune system. This study aimed to evaluate and compare the in vivo performance of three commercially-available synthetic bone grafts, (1) i-FACTOR Putty. ®. , (2) OssDsign. ®. Catalyst Putty and (3) FIBERGRAFT. ®. BG Matrix, with that of a novel synthetic bone graft in a clinically-relevant instrumented sheep posterolateral lumbar spine fusion (PLF) model. The novel synthetic bone graft comprised of BCP granules with a needle-shaped submicron surface topography (MagnetOs) embedded in a highly porous and fibrillar collagen matrix (MagnetOs Flex Matrix). Four synthetic bone grafts were implanted as standalone in an instrumented sheep PLF model for 12 weeks (n=3 bilateral levels per group; levels L2/3 & L4/5), after which spinal fusion was determined by manual palpation, radiograph and µCT imaging (based on the Lenke scale), range-of-motion mechanical testing, and histological and histomorphological evaluation. Radiographic fusion assessment determined bilateral robust bone bridging (Lenke scale A) in 3/3 levels for MagnetOs Flex Matrix compared to 1/3 for all other groups. For µCT, bilateral fusion (Lenke scale A) was found in 2/3 levels for MagnetOs Flex Matrix, compared to 0/3 for i-FACTOR Putty. ®. , 1/3 for OssDsign. ®. Catalyst Putty and 0/3 for FIBERGRAFT. ®. BG Matrix. Fusion assessment for MagnetOs Flex Matrix was further substantiated by histology which revealed significant graft resorption complemented by abundant bone tissue and continuous bony bridging between vertebral transverse processes resulting in bilateral spinal fusion in 3/3 implants. These results show that MagnetOs Flex Matrix achieved better fusion rates compared to three commercially-available synthetic bone grafts when used as a standalone in a clinically-relevant instrumented sheep PLF model

Cervical and lumbar spine fusion procedures are increasing every year. Nonetheless, these procedures are associated with high infection rates, resulting in additional cost burden. The conundrum of achieving efficient spinal fusions with minimum complications requires an ideal bone graft with osteoconductive, osteoinductive, osteogenic and structural characteristics. Synthetic bone graft substitutes with or without autograft, allograft or synthetic bone substitutes have been commonly used for fusion procedures. We carried out a meta-analysis of comparative studies and prospective case series (n = 29) with cervical and lumbar fusion procedures using synthetic bone graft substitutes, autograft or allograft and other biologics. Synthetic bone graft substitutes analysed included HA (Hydroxyapatite), β-TPC (Tri Calcium Phosphate), β-TSC (Tri Calcium Sulfate), PMMA (Polymethylmetacrylate), Surgibone, BOP (Biocompatible Osteoconductive Polymer). The analysis revealed suboptimal evidence for the efficacy and safety of synthetic products used in spinal fusion procedures. Further studies are needed to determine beneficial effects of synthetic substitutes. However, the infection rate could be highly decreased with surface and composition modification of widely used polyether ether ketone (PEEK) implants. Laser modification of surface characteristics and collagen fleeces with micro and nano pore structures can prove to be excellent surface for increased osteoblasts cell proliferation and vitality

Spinal fusion is one of the most common surgical procedures in spine surgery, whose primary objective is the stabilization of the spine for the treatment of many degenerative, traumatic and oncological diseases of the spine. Autologous bone is still considered the “gold standard” technique for spinal fusion. However, biomaterials which are potentially osteogenic, osteoinductive and osteoconductive can be used to increase the process of spinal fusion. We evaluated two new bone substitutes as an alternative to autologous bone for spinal fusion, using an animal model of large size (adult sheep). A preclinical study was designed to compare the efficacy of SINTlife® Putty and DBSINT® biomaterials with conventional bone autograft in an ovine model of lumbar spine fusion. SINTlife® is a biomaterial made from hydroxyapatite enriched with magnesium ions, resulting to be very similar to natural bone. DBSint® is a paste composite bone, osteo-inductive, pliable and conformable, consisting of demineralized bone matrix (DBM) carried by hydroxyapatite biomimetics. Eighteen adult female sheep were selected for two-levels spine surgical procedures. The animals were divided in two groups: in Group A, one fusion level was treated with SINTlife® Putty and the other level received cortical-cancellous bone autograft; in Group B, one fusion level was treated with DBSINT® and the other level received cortical-cancellous bone autograft. At the end of the experimental time, all the animals were euthanized. The spine segments were analyzed macroscopically, radiographically, microtomographically, histologically and histomorphometrically. The SINT-Life® Putty shows a perfect osteointegration in all the histological specimens. A high percentage of newly formed bone tissue is detected, with lots of trabeculae having structure and morphology similar to the pre-existing bone. In all the specimens collected from DBSINT®-treated animals the presence of hydroxyapatite alone is reported but not the demineralized bone matrix. The presence of newly formed bone tissue can be detected in all the specimens but newly formed bone shows very thin and irregular trabeculae next to the cartilage zone, while away from the border of ossification there are thicker trabeculae similar to the pre-existing bone. The use of the experimental biomaterial SINT-Life® Putty in an ovine model of spine fusion leads to the development of newly formed bone tissue without qualitative and quantitative differences with the one formed with autologous bone. The experimental material DBSINT® seems to lead to less deposition of newly formed bone with wider intertrabecular spaces. Following these results, we planned and submitted to the Ethical Committee a clinical study to evaluate the safety and efficacy of SINT-Life® product in comparison to autologous bone, as an alternative treatment for spine fusion procedures

Objective

Lumbar spinal stenosis (LSS) is a common spinal disorder mostly caused by the arthritic process. In cases with refractory complaints or significant neurologic deficit, decompressive surgery with or without instrumented fusion may be indicated. We aimed to investigate the surgical outcome of multi-level LSS in the patient with stable spine treated by simple decompression versus decompression and instrumented fusion. Methods: We retrospectively studied 51 patients (25 male, 26 female) with stable multi-level (>2 levels) LSS who were treated by decompressive surgery alone (group A, 31 cases) and decompression and instrumented fusion (group B, 20 cases) and followed them for more than two years. The patients’ disability and pain were assessed with Oswestry Disability Index (ODI) and Visual Analogue Scale (VAS), respectively. At the last follow-up visit, patient satisfaction with surgery was also scored. Results: The two groups were homogeneous in terms of age, sex, severity of disability and pain. Surgery could significantly improve pain and disability in both groups. Preoperative ODI in group A and B were 51.0±23.7 and 54.5±22.9, respectively, however at the last follow-up visit these parameters improved to 23.1±21.1 and 36.6±21.4 showing a statistical significance. Mean patient satisfaction with surgical intervention was also higher in the simple decompression group, but this difference was not significant. Conclusion: In surgical treatment of the patients with multi-level but stable LSS, simple decompression versus decompression and instrumented fusion could achieve more disability improvement for more than two years of follow-up.

Chronic low back pain (CLBP) is the most common cause of disability worldwide, and lumbar spine fusion (LSF) is often chosen to treat pain caused by advanced degenerative disease when clinical treatment failed certain cases, the post-surgical outcomes are not what was expected. Several studies highlight how important are. In psychological variables during the postoperative spine surgery period. The aim of this study is to assess the role of preoperative depression on postoperative clinical outcomes. We included patients who underwent LSF since December 2021. Preoperative depression was assessed administering Beck Depression Inventory questionnaire (BDI). And pain and disability were evaluated at 1, 3, and 6 months, administering respectively Visual Analogic Scale (VAS) and Oswestry Disability Index (ODI). As statistical analysis Mann-Whitney test was performed. We included 46 patients, 20 female (43,5%) and 26 male (56,5%) with an average age of 64,2. The population was divided in two groups, fixing the BDI cut-off point at 10. Patients with BDI < 10 points (N=28) had normal mental health status, instead patients with BDI > 10 points (N=16) had depressive disorders. At 3 months patients with healthy mental status reported statistically significant reduction of pain (U = 372,5, p = .006) and improvement of disability but without statistical significancy (U = 318, p = 0,137). At 6 months patients without psychological disease reported statistically significant reduction of pain (U = 342, p = 0,039) and disability (U = 372,5, p = 0,006). This study demonstrates the correlation between pre-existing depressive state and poorer clinical outcomes after spine surgery. These results are consistent with the literature. Therefore, during the surgical decision making it is crucial to take psychological variables into account in order to predict the results after surgery and inform patients on the potential influence of mental status

Posterior spinal surgery is associated with a significant amount of blood loss. The factors predisposing the patient to excessive bleeding-and therefore transfusion- are not well established nor is the effect of transfusion on the outcomes following spinal surgery. We had two goals in this study. First, we were to investigate any suspected risk factors of transfusion in posterior thoraco-lumbar fusion patients. Second, we wanted to observe the negative impact-if one existed- of transfusion on the outcomes of surgery. All adults undergoing posterior thoraco-lumbar spine fusion in our institution from May 2015 to May 2018 were included. Data collected included demographic data as well as BMI, preoperative hemoglobin, American Society of Anesthesiologists classification (ASA), delta Hemoglobin, estimated blood loss, incidence of transfusion, number of units transfused, number of levels fused, length of stay and re-admission within 30 days. The data was analyzed to correlate these variables with the frequency of transfusion and then to assess the association of adverse outcomes with transfusion. 125 patients were included in the study. Only 6 patients (4.8%) required re-admission within the first 30 days after discharge. Length of stay averaged 8.4 days (3–74). 18 patients (14.4%) required transfusion peri-operatively. When multiple variables were analyzed for any correlation, the number of levels fused, age and BMI had statistically significant correlation with the need for transfusion (P <0.005). Patients undergoing posterior thoraco-lumbar fusion are more likely to require blood transfusion if they were older, over-weight & obese or had a multi-level fusion. Receiving blood transfusion is associated with increased complication rates

Background context. Fusion is a fundamental procedure in spine surgery. Although autogenous grafts have ideal bone graft characteristics, their use may remain limited due to various morbidities. Even though ceramic based synthetic bone grafts are used commonly at present, in order to enhance their efficacy, their combined use with other materials has been investigated. The use of carbon nanotubes (CNTs) together with synthetic bone grafts such as hydroxyapatite (HA) has contributed to positive developments in bone tissue engineering. Purpose. The aim of the present study was to investigate the effect of CNTs/ HA- tricalcium phosphate (TCP) composite prepared in posterolateral spinal fusion model. Study Design/Setting. Experimental animal study. Methods. At first, CNTs and CNTs/HA-TCP composites were prepared. Twenty adult male Spraque Dawley rats were randomized into four groups with five rats in each group. Decortication was carried out in standard manner in all animals. Group 1 (only decortication), group 2 (CNTs), group 3 (HA-TCP) and group 4 (CNTs/HA-TCP) were formed. Eight weeks later all animals were sacrificed and obtained fusion segments were evaluated by manual palpation, histomorphometry and micro computed tomography (mCT). Results. In all evaluations, highest fusion values were obtained in Group 4. In mCT investigations, bone volume/ tissue volume (BV/TV) ratio was found to be significantly higher in composite group (group 4) only compared to ceramic group (group 3). Although in Group 2, in which only CNTs were used, the ratio was found to be significantly higher than group 1, the difference was not considered significant in terms of fusion and in addition in group 2, CNTs were completely surrounded by fibrous tissue, i.e. no bone formation was observed. Conclusions. The combined use of carbon nanotubes with ceramic based bone grafts enhances spinal fusion markedly. Although CNTs are inadequate in producing spinal fusion when they are used by themselves, due to especially their high biocompatibillity and unique bicomechanic characteristics compatible with bone tissue, they increase fusion rates significantly, particularly together with ceramic based synthetic grafts. Keywords. Spinal fusion; Rat; Carbon nanotube(s); Ceramic(s); Bone graft subsitutes; Hydroxyapatite

Due to well-known disadvantages of the autologous bone graft, many alternatives have been studied for a reliable spinal fusion. Herein, we aimed to investigate the effects of human recombinant epidermal growth factor (EGF) on posterolateral lumbar fusion in a rat model. 36 male SD rats underwent posterolateral fusion at L4-5 level. They were randomly assigned to 3 groups: Sham control group, Hydoxyapatite β-tricalcium phosphate (HA/β-TCP) group and HA/β-TCP + EGF group. Rats were euthanized at 8 weeks post-surgery. 6 rats from each group were selected for manual palpation examination, micro-computed tomography analysis and histologic analysis; and the rest was used for biomechanical analysis. Based on manual palpation, there was no fusion in the sham control group. Fusion rate was 33.3% in the HA/β-TCP group and 66.7% in the HA/β-TCP + EGF group (p=0.085). Micro-CT results revealed that new bone formation was higher in the HA/β-TCP + EGF group (BV/TV: 40% vs. 65%) (p=0.004). Histologically newly formed bone tissue was more pronounced in the EGF group and compacted and bridging bone spicules were observed. The median maximum bending moment values were 0.51 Nmm (0.42– 0.59), 0.73 Nmm (0.49– 0.88) and 0.91 Nmm (0.66– 1.03) in the sham control, HA/β-TCP and HA/β-TCP + EGF groups, respectively (p=0.013). The median stiffness values were 1.69 N/mm (1.12–2.18), 1.68 N/mm (1.13–2.74) and 3.10 N/mm (1.66–4.40) as in the previous order (p=0.087). This study demonstrates that EGF enhances posterolateral lumbar fusion in the rat model. EGF in combination with ceramic grafts increased the fusion rates

Aternatives to autogenous bone graft for spinal fusion have been investigated for many years. It has been shown that osteoconductive materials alone do not give a rate of fusion which is comparable to that of autogenous bone graft. We analysed the effectiveness of porous ceramic loaded with cultured mesenchymal stem cells as a new graft material for spinal fusion in an animal model. Posterolateral fusion was carried out at the L4/L5 level in 40 White New Zealand rabbits using one of the following graft materials: porous ceramic granules plus cultured mesenchymal stem cells (group I); ceramic granules plus fresh autogenous bone marrow (group II); ceramic granules alone (group III); and autogenous bone graft (group IV). The animals were killed eight weeks after surgery and the spines were evaluated radiographically, by a manual palpation test and by histological analysis. The rate of fusion was significantly higher in group I compared with group III and higher, but not significantly, in group I compared with groups II and IV. In group I histological analysis showed newly formed bone in contact with the implanted granules and highly cellular bone marrow between the newly formed trabecular bone. In group II, thin trabeculae of newly formed bone were present in the peripheral portion of the fusion mass. In group III, there was a reduced mount of newly formed bone and abundant fibrous tissue. In group IV, there were thin trabeculae of newly formed bone close to the decorticated transverse processes and dead trabecular bone in the central portion of the fusion mass. In vitro cultured mesenchymal stem cells may be loaded into porous ceramic to make a graft material for spinal fusion which appears to be more effective than porous ceramic alone. Further studies are needed to investigate the medium- to long-term results of this procedure, its feasibility in the clinical setting and the most appropriate carrier for mesenchymal stem cells

The current study aims to compare the clinico radiological outcomes between Non-Fusion Anterior Scoliosis (NFASC) Correction and Posterior Spinal Fusion (PSF) for Lenke 5 curves at 2 years follow up. Methods:38 consecutive Lenke 5 AIS patients treated by a single surgeon with NFASC (group A) or PSF (group B) were matched by age, Cobb's angle, and skeletal maturity. Intraoperative blood loss, operative time, LOS, coronal Cobbs, and SRS22 scores at 2 years were compared. Flexibility was assessed by modified Schober's test. Continuous variables were compared using student t-tests and categorical variables were compared using chi-square. The cohort included 19 patients each in group A and B . Group A had M:F distribution of 1:18 while group B had 2:17. The mean age in group A and group B were 14.8±2.9 and 15.3±3.1 years respectively. The mean follow-up of patients in groups A and B were 24.5±1.8 months and 27.4±2.1 months respectively. Mean pre-op thoracolumbar/lumbar (TL/L) cobbs for group A and group B were 55°±7° and 57.5°±8° respectively. At two years follow up, the cobbs for group A and B were 18.2°±3.6° and 17.6°±3.5° respectively (p=0.09). The average operating time for groups A and B were 169±14.2 mins and 219±20.5 mins respectively (p<0.05). The average blood loss of groups A and B were 105.3±15.4 and 325.3±120.4 respectively (p<0.05). The average number of instrumented vertebra between groups A and B were 6.2 and 8.5 respectively (p<0.05). The average LOS for NFASC and PSF was 3.3±0.9 days and 4.3±1.1 days respectively (p<0.05). No statistically significant difference in SRS 22 score was noted between the two groups. No complications were recorded. Our study shows no significant difference in PSF and NFASC in terms of Cobbs correction and SRS scores, but the NFASC group had significantly reduced blood loss, operative time, and fewer instrumented levels. NFASC is an effective alternative technique to fusion to correct and stabilize Lenke 5 AIS curves with preservation of spinal motion

Pseudoarthrosis after spinal fusion is an important complication leading to revision spine surgeries. Iliac Crest Bone Graft is considered the gold standard, but with limited availability and associated co-morbidities, spine surgeons often utilize alternative bone grafts. Determine the non-inferiority of a novel submicron-sized needle-shaped surface biphasic calcium phosphate (BCP<µm) as compared to autograft in instrumented posterolateral spinal fusion. Adult patients indicated for instrumented posterolateral spinal fusion of one to six levels from T10-S2 were enrolled at five participating centers. After instrumentation and preparation of the bone bed, the randomized allocation side of the graft type was disclosed. One side was grafted with 10cc of autograft per level containing a minimum of 50% iliac crest bone. The other side was grafted with 10cc of BCP<µm granules standalone (without autograft or bone marrow aspirate). In total, 71 levels were treated. Prospective follow-up included adverse events, Oswestry Disability Index (ODI), and a fine-cut Computerized Tomography (CT) at one year. Fusion was systematically scored as fused or not fused per level per side by two spine surgeons blinded for the procedure. The first fifty patients enrolled are included in this analysis (mean age: 57 years; 60% female and 40% male). The diagnoses included deformity (56%), structural instability (28%), and instability from decompression (20%). The fusion rate determined by CT for BCP<μm was 76.1%, which compared favorably to the autograft fusion rate of 43.7%. Statistical analysis through binomial modeling showed that the odds of fusion of BCP<μm was 2.54 times higher than that of autograft. 14% of patients experienced a procedure or possible device-related severe adverse event and there were four reoperations. Oswestry Disability Index (ODI) score decreased from a mean of 46.0 (±15.0) to a mean of 31.7 (±16.9), and 52.4% of patients improved with at least 15-point decrease. This data, aiming to determine non-inferiority of standalone BCP<μm as compared to autograft for posterior spinal fusions, is promising. Ongoing studies to increase the power of the statistics with more patients are forthcoming

Abstract. Objectives. While spinal fusion is known to be associated with adjacent disc degeneration, little is known on the role of the facet joints in the process, and whether their altered biomechanics following fusion plays a role in further spinal degeneration. This work aimed to develop a model and method to sequentially measure the effects of spinal fusion on lumbar facet joints through synchronisation of both motion analysis, pressure mapping and mechanical analysis. Methods. Parallel measurements of mature ovine lumbar facet joints (∼8yr old, n=3) were carried out using synchronised load and displacement measurements, motion capture during loading and pressure mapping of the joint spaces during loading. Functional units were prepared and cemented in PMMA endcaps. Displacement-controlled compression measurements were carried out using a materials testing machine (3365, Instron, USA) at 1 mm/min up to 950 N with the samples in a neutral position, while motion capture of the facet joints during compression was carried out using orthogonal HD webcams (Logitech, Switzerland) to measure the displacement of key facet joint features. The pressure mapping of load transfer during displacement was carried out using a flexible pressure sensor (6900 series, Tekscan, USA). Each sample was imaged at an isotropic resolution of 82 microns using a μCT scanner (XtremeCT, Scanco, Switzerland) to quantify the curvature within the facet joints. Results. Relative facet joint displacement under load, in a neutral position, showed more displacement (2.36 ±1.68 mm) compared to the cross-head when under compression (2.06 ±1.19 mm). Motion capture indicated the relative displacement of the facet joints was more posterior with some lateral motion. For five of the six facet joints, pressure measurement was possible only on 24±7 % of the surface due to the large change in curvature. Partially measured loads through the facets was 10.5 ±1.1 N. Conclusions. The relative displacement of the lumbar facet joints compared to the crosshead displacement was consistent with previous studies of cervical facet joints, despite the differences in anatomical geometry between cervical and lumbar joints. The difficulties in accurately measuring the load transfer through the facet joints was due to the age of the tissue and the degree of curvature of the facet joints. Synchronisation of the biomechanical data will provide a setup to assess the effect of interventions such as spinal fusion, with curvature-related issues unlikely to occur in human spines. Declaration of Interest. (a) fully declare any financial or other potential conflict of interest

Due to the presence of megakaryocytes, platelets and clotting factors, bone marrow aspirate (BMA) tends to coagulate. For the first time, starting from our previous studies on mesenchymal vertebral stem cells, it has been hypothesized that coagulated BMA represents a safe and effective autologous biological scaffold for bone regeneration in spinal surgery. The present research involved advanced preclinical in vitro models and the execution of a pilot clinical study. Evaluation of cell morphology, growth kinetics, immunophenotyping, clonogenicity, trilineage-differentiation, growth-factors and HOX and TALE gene expression were analyzed on clotted- and un-clotted human V-BMA. In parallel, a pilot clinical study on ten patients with degenerative spine diseases submitted to instrumented posterior arthrodesis, is ongoing to assess the ability of clotted-V-BMA to improve spinal fusion at 6- and 12-months follow-up. Results demonstrated that clotted-V-BMA have significantly higher growth-factor expression and mesenchymal stem cell (MSCs) viability, homogeneity, clonogenicity, and ability to differentiate towards the osteogenic phenotype than un-clotted-V-BMA. Clotted-V-BMA also highlighted significant reduced expression of PBX1 and of MEIS3 genes negatively involved in osteoblast maturation and differentiation. From December 2020, eight patients have already been enrolled with first promising results that will be finally evaluated in the next two months. The application of V-BMA-clot as carrier of progenitors and cytokines and as natural scaffold with a structural texture represents a point-of-care orthobiologic product to improve spinal fusion. Clinical application seems to be efficacy, and we will confirm and strengthen these data with the final results of the pilot clinical study

To prevent the reported side effects of rhBMP-2, an important cytokine with bone forming capacity, the sustained release of rhBMP-2 is highly important. Synthetic copolymer polylactic acid-polyethylene glycol (PLA-PEG) is already shown to be a good carrier for rhBMP-2. The nano-sized hydroxyapatite (nHAp) is mentioned to be superior to conventional hydroxyapatite due to its decreased particle size which increases the surface area, so protein-cell adhesion and mechanical properties concomitantly. In the literature no study is reported with PLA-PEG / rhBMP-2/ nHAp for bone regeneration. In this study, we assessed the controlled release profile of rhBMP-2 from the novel biomaterial of PLA-PEG / rhBMP-2 / nHAp in vitro and evaluated the bone forming capacity of the composite in rat posterolateral spinal fusion (PSF) model in vivo. Composites were prepared via addition of rhBMP-2 (0µg, 3µg or 10µg) and nHAp (12.5mg) into PLA-PEG (5mg) + acetone solution and shaping. The release kinetics of the cytokine from the composites with 5µg BMP-2 was investigated by ELISA. The effect of nHAp and nHAp with rhBMP-2 on cell differentiation (rat BMSC cells, passage 3) was tested with ALP staining. In vivo bone formation was investigated by PSF on L4-L5 in a total of 36 male SD rats and weekly µCT results and histology at 8. th. weeks post operation were used for assessment of the bone formation. All animal experiments was approved by the institutional review board confirming to the laws and regulations of Japan. The composite showed an initial burst release in the first 24 hours (51.7% of the total released rhBMP-2), but the release was continued for the following 21 days. Thus, the sustained release of rhBMP-2 from the composite was verified. ALP staining results showed nHAp with rhBMP-2 contributed better on differentiation than nHAp itself. µCT and histology demonstrated that spinal fusion was achieved either one or both transverse processes in almost all BMP 3µg and BMP 10µg treated animals. On the contrary, only small or no bone formation was observed in the BMP0µg group (bilateral non-union / unilateral fusion/ bilateral fusion, BMP0µg group; 9/0/0, BMP3µg group; 1/0/11, BMP10µg group; 0/1/11). We developed a new technology for bone regeneration with BMP-2/PLA-PEG/nHAp composite. With this composite, the required dose of BMP-2 for spinal fusion in rats (10µg) was decreased to 1/3 (3µg) which can be explained by the superior properties of nano-sized hydroxyapatite and by the achievement of sustainable release of rhBMP-2 from the composite. This study is supported by Japanese Society of the Promotion of Science (JSPS) and Scientific and Technological Research Council of Turkey (TUBITAK). [Project No: 215S834]

With the increase in the elderly population, there is a dramatic increase in the number of spinal fusions. Spinal fusion is usually performed in cases of primary instability. However it is also performed to prevent iatrogenic instability created during surgical treatment of spinal stenosis in most cases. In literature, up to 75% of adjacent segment disease (ASD) can be seen according to the follow-up time. 1. Although ASD manifests itself with pathologies such as instability, foraminal stenosis, disc herniation or central stenosis. 1,2. There are several reports in the literature regarding lumbar percutaneous transforaminal endoscopic interventions for lumbar foraminal stenosis or disc herniations. However, to the best our knowledge, there is no report about the treatment of central stenosis in ASD. In this study, we aimed to investigate the short-term results of unilateral biportal endoscopic decompressive laminotomy (UBEDL) technique in ASD cases with symptomatic central or lateral recess stenosis. The number of patients participating in the prospective study was 8. The mean follow-up was 6.9 (ranged 6 to 11) months. The mean age of the patients was 68 (5m, 3F). The development of ASD time after fusion was 30.6 months(ranged 19 to 42). Mean fused segments were 3 (ranged 2 to 8). Preoperative instability was present in 2 of the patients which was proven by dynamic lumbar x-rays. Preoperative mean VAS-back score was 7.8, VAS Leg score was 5.6. The preoperative mean JOA (Japanese Orthopaedic Association) score was 11.25. At 6th month follow-up, the mean VAS back score of the patients was 1, and the VAS leg score was 0.5. This improvement was statistically significant (p = 0.11 and 0.016, respectively). The mean JOA score at the 6th month was 22.6 and it was also statistically significant comparing preoperative JOA score(p = 0.011). The preoperative mean dural sac area measured in MR was 0.50 cm2, and it was measured as 2.1 cm. 2. at po 6 months.(p = 0.012). There was no progress in any patient's instability during follow-up. In orthopedic surgery, when implant related problems develop in any region of body (pseudoarthrosis, infection, adjacent fracture, etc.), it is generally treated by using more implants in its final operation. This approach is also widely used in spinal surgery. 3. However, it carries more risk in terms of devoloping ASD, infection or another complications. In the literature, endoscopic procedures have almost always been used in the treatment of ventral pathologies which constitute only 10%. In ASD, disease devolops as characterized by wide facet joint arthrosis and hypertrophied ligamentum flavum in the cranial segment and it is mostly presented both lateral recess and santal stenosis symptoms (39%). In this study, we found that UBEDL provides successful results in the treatment of patients without no more muscle and ligament damage in ASD cases with spinal stenosis. One of the most important advantages of UBE is its ability to access both ventral and dorsal pathologies by minimally invasive endoscopic aproach. I think endoscopic decompression also plays an important role in the absence of additional instability at postoperatively in patients. UBE which has already been described in the literature given successful results in most of the spinal degenerative diseases besides it can also be used in the treatment of ASD. Studies with longer follow-up and higher patient numbers will provide more accurate results

Sustained release of BMP-2 is reported to be able to reduce the required dose of BMP-2 for bone induction. Nanohydroxyapatite (nHAp) has an osteoinduction capability which is lack in conventional hydroxyapatite. In this study, we combined PLA-PEG with nHAp and investigated the bone regenerative capacity of the newly established composite material of rhBMP-2/PLA-PEG/nHAp in a rat model of spinal fusion. The PLA-PEG was liquidized in acetone and mixed with nHAp and rhBMP-2. The sheet-shaped BMP-2/PLA-PEG (5mg)/nHAp (12.5mg) composites were prepared while evaporating the acetone. The release kinetics of rhBMP-2 from the composite was investigated by ELISA. In vivo bone formation was investigated by posterolateral spinal fusion in rats (the dosage of rhBMP-2; 0µg/ 0.5µg / 3µg). Bone formation was assessed by µCT and histology at post-op. 8 weeks. The composite showed the burst-release in the initial 24 hours (69% of total release) and the subsequent sustained-release for 25 days. According to µCT and histology of the spinal fusion experiment for all groups the bone formation was observed. While no bony bridging was observed in 0 µg and 0.5 µg BMP groups; in 3 µg group bony bridging and fusion were achieved. We developed a new technology for bone regeneration with rhBMP-2/PLA-PEG/nHAp composite. The reduction in the required dose of BMP-2 for bone induction was achieved. This result can be explained by the high bone induction ability of nHAp and sustainable release of BMP from PLA-PEG in the composite

AO Spine Guideline for Using Osteobiologics in Spine Degeneration project is an international collaborative initiative to identify and evaluate evidence on existing use of osteobiologics in spine degenerative diseases. It aims to formulate clinically relevant and internationally applicable guidelines ensuring evidence-based, safe and effective use of osteobiologics. The current focus is the use of osteobiologics in anterior cervical discectomy and fusion surgeries. The guideline development is planned in three phases. Phase 1- Evidence synthesis and Recommendation; Phase 2- Guideline with osteobiologics grading and Validation; Phase 3- Guideline dissemination and Development of a clinical decision support tool. The key questions formulating the guidelines for the use of osteobiologics will be addressed in a series of systematic reviews in Phase 1. The evidence synthesized by the systematic reviews will be assessed by Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology, including expert panel discussions to formulate a recommendation. In Phase 2, osteobiologics will be graded based on evidence and the grading will be integrated with the recommendation from Phase 1, and thus formulate a guideline. The guideline will be further validated by prospective clinical studies. In the third phase, dissemination of the proposed guideline and development of a decision support tool is planned. AO-GO aims to bridge an important gap between quality of evidence and use of osteobiologics in spine fusion surgeries. With a holistic approach the guideline aims to facilitate evidence-based, patient-oriented decision-making process in clinical practice, thus stimulating further evidence-based studies regarding osteobiologics usage in spine surgeries