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Background The use of bone morphogenic protein (BMP-2) in adult spine deformity (ASD) surgery remains controversial more than two decades following its approval for clinical application in spine surgery. This study was performed to assess outcomes in patients undergoing ASD surgery with BMP application compared with a combination of bone marrow aspirate, cancellous bone chips and i-Factor.MethodsThis was a retrospective cohort study. ASD patients were stratified by use of intra-operative BMP (BMP +) or not (BMA + I) and surveyed for the development of complications and mechanical failure. Quality of life gained following the procedure was evaluated using quality-adjusted life years (QALYs). Cost was calculated using the PearlDiver database and CMS definitions. Multivariable analyses (ANCOVA) and logistic regression were used to adjust for confounding.Results512 patients were included (60% BMP +). At baseline, BMP + patients were older (62.5 vs 60.8 years, p < 0.010). Radiographic and quality-of-life metrics did not differ at follow up timepoints (all p > 0.05). BMP use was associated with higher supplemental rod use (OR: 7.0, 1.9 – 26.2, p = 0.004), greater number of levels fused (OR: 1.1, 1.03 – 1.17, p = 0.003) and greater neurological complications (OR: 5.0, 1.3 – 18.7, p = 0.017). Controlling for rod use and levels fused, BMP use was not associated with a lower risk of mechanical complications (OR 0.3, 95% CI: 0.2 – 3.0, p = 0.353), rod breakage (OR: 3.3, 0.6 – 18.7, p = 0.182) or implant failure (OR: 0.3, 0.04 – 1.51). At 2 years, the BMP + cohort exhibited higher overall costs ($108,062 vs $95,144, p = 0.002), comparable QALYs (0.163 vs 0.171, p = 0.65) and higher cost per QALY (p = 0.001) at two years.ConclusionsIn this analysis, BMP-2 application was not associated with superior outcomes when compared to a less costly biologic alternative (bone marrow aspirate + cancellous bone chips + i-Factor) following ASD surgery. The use of BMP-2 in ASD surgery appears to have reduced cost-efficacy at two years postoperatively.

Purpose Cell-based therapies such as concentrated bone marrow aspirate (BMA) with allograft and demineralized bone matrix (DBM) have been developed as a potential alternative to iliac crest bone graft (ICBG) in spinal fusion. BMA contains mesenchymal stem cells (MSCs) and growth factors that confer osteogenic and osteoinductive potential to osteoconductive scaffolds like allograft and DBM. It is well established that there is an age-related decline in bone marrow MSC population and efficacy. This might be problematic in spine arthrodesis when utilizing BMA derived from elderly patients as a fusion aide. The goal of this study was to describe the outcomes of concentrated BMA with allograft and DBM in elderly patients undergoing posterolateral and interbody lumbar fusion. Methods Thirty-one patients, age 65 and older, with a minimum of 12 months follow-up underwent combined primary posterolateral and transforaminal lumbar interbody fusion. Radiographic fusion, complications, reoperation rates and clinical outcomes were assessed. Multiple logistic regression analysis was used to examine the effects of variables such as patient age, gender, smoking, osteoporosis, Charlson co-morbidity index score, single versus multilevel fusion, length of hospital stay, and length of follow-up time on fusion outcome. Results The overall rate of a solid fusion (i.e. the concomitant presence of solid posterolateral and interbody fusion in a patient) was 83.9 % (26/31). Specifically, radiographic evidence of a successful posterolateral fusion was 83.9 % (26/31) while the radiographic evidence of a successful interbody fusion was 96.8 % (30/31). Using logistic regression analysis, none of the variables of interest had an association with non-solid unions. One (3.2 %) patient developed a seroma and one (3.2 %) patient developed clinical pseudarthrosis. None of the patients developed hardware-related complications or graft donor site morbidities. Five (16.1 %) patients required reoperation. Excellent or good results were achieved in 83.9 % of patients. Conclusions Despite the concerns of reduced fusion potential in elderly patients, autologous concentrated BMA mixed with allograft and DBM in posterolateral and interbody fusions can achieve successful fusion rates with good clinical outcomes and low complication rates.

Critical-sized bone defects are defined as those that will not heal spontaneously within a patient’s lifetime. Current treatment options include vascularized bone grafts, distraction osteogenesis, and the induced membrane technique. The induced membrane technique is an increasingly utilized method with favorable results including high rates of union. Tissue engineering holds promise in the treatment of large bone defects due to advancement of stem cell biology, novel biomaterials, and 3D bioprinting. In this review, we provide an overview of the current operative treatment strategies of critical-sized bone defects as well as the current state of tissue engineering for such defects.

Bone allografts donated by other individuals offer a viable alternative to autograft. Risks of disease transmission are overcome by sterilizing the bone; unfortunately sterilization methods generally affect bone functional properties including osteogenic potential and biomechanical integrity. This study aimed to determine any enhancement effect when gamma sterilised allografts was impregnated with autologous bone marrow in improving the rate and quality of integration in metaphyseal-tibial defects of rabbits. Almost all subjects showed 50% of the defect being covered by new bones by the third week and smaller residual defect size in the treated group at the fifth week. Hounsfield units at the defect site showed increasing healing in all samples, with the treated group having an apparent advantage although insignificant (p > 0.05). In the histopathological score evaluating healing over cortical and cancellous bone at the fracture site showed only slight variations between the groups (p > 0.05). Therefore no enhanced healing by the autologous bone marrow was observed when added to the bone allografts in treating the unicortical defects.

Although several human clinical trials using various bone marrow-derived cell types for cirrhotic or decompensated patients have reported a short-term benefit, long-term follow-up data are limited. We analyzed the long-term clinical outcomes of autologous bone marrow cell infusion (ABMI) for decompensated liver cirrhosis (LC). Patients enrolled in a pilot single-armed ABMI study were followed up more than 5 years. Bone marrow-derived mononuclear cells (BM-MNCs) from decompensated LC were harvested and after processing were infused into a peripheral vein. The laboratory test results and long-term clinical course including liver transplantation (LT), development of cancer, cause of death, and survival after ABMI were analyzed. Nineteen patients were followed up for a median of 66 months after ABMI. Liver function, including serum levels of albumin and Child–Pugh (CP) score, was improved at the 1-year follow-up. Liver volume was significantly greater, cirrhosis was sustained, and collagen content was decreased at the 6-month follow-up. Five years after ABMI, five patients (26.3%) maintained CP class A without LT or death, and five patients (26.3%) had undergone elective LT. Hepatocellular carcinoma (HCC) occurred in five patients (26.3%), and lymphoma and colon cancer occurred in one patient each. Three patients (15.8%) were lost to follow-up at months 22, 31, and 33, respectively, but maintained CP class A until their last follow-up. Five patients expired due to infection. While improved liver function was maintained in some patients for more than 5 years after ABMI, other patients developed HCC. Further studies of long-term follow-up cohorts after cell therapy for LC are warranted.

Purpose Due to the disadvantages of iliac crest bone and the poor bone quality of autograft gained from decompression surgery, alternative filling materials for posterior lumbar interbody fusion cages have been developed. β-Tricalcium phosphate is widely used in cages. However, data regarding the fusion rate of β-TCP assessed by computer tomography are currently not available. Materials A prospective clinical trial involving 34 patients (56.7 years) was performed: 26 patients were treated with single-level, five patients double-level and three patients triple-level PLIF filled with β-TCP and bone marrow aspirate perfusion, and additional posterior pedicle screw fixation. Fusion was assessed by CT and X-rays 1 year after surgery using a validated fusion scale published previously. Functional status was evaluated with the visual analogue scale and the Oswestry Disability Index before and 1 year after surgery. Results Forty-five levels in 34 patients were evaluated by CT and X-ray with a follow-up period of at least 1 year. Clinically, the average ODI and VAS for leg and back scores improved significantly ( P  < 0.001). CT assessment revealed solid fusion in 12 levels (26.67 %) and indeterminate fusion in 15 levels (34.09 %). Inadequate fusion (non-union) was detected in 17 levels (38.63 %). Conclusion The technique of PLIF using β-TCP yielded a good clinical outcome 1 year after surgery, however, a high rate of pseudoarthrosis was found in this series therefore, we do not recommend β-TCP as a bone graft substitute using the PLIF technique.

Bone substitutes are being increasingly used in surgery as over two millions bone grafting procedures are performed worldwide per year. Autografts still represent the gold standard for bone substitution, though the morbidity and the inherent limited availability are the main limitations. Allografts, i.e. banked bone, are osteoconductive and weakly osteoinductive, though there are still concerns about the residual infective risks, costs and donor availability issues. As an alternative, xenograft substitutes are cheap, but their use provided contrasting results, so far. Ceramic-based synthetic bone substitutes are alternatively based on hydroxyapatite (HA) and tricalcium phosphates, and are widely used in the clinical practice. Indeed, despite being completely resorbable and weaker than cortical bone, they have exhaustively proved to be effective. Biomimetic HAs are the evolution of traditional HA and contains ions (carbonates, Si, Sr, Fl, Mg) that mimic natural HA (biomimetic HA). Injectable cements represent another evolution, enabling mininvasive techniques. Bone morphogenetic proteins (namely BMP2 and 7) are the only bone inducing growth factors approved for human use in spine surgery and for the treatment of tibial nonunion. Demineralized bone matrix and platelet rich plasma did not prove to be effective and their use as bone substitutes remains controversial. Experimental cell-based approaches are considered the best suitable emerging strategies in several regenerative medicine application, including bone regeneration. In some cases, cells have been used as bioactive vehicles delivering osteoinductive genes locally to achieve bone regeneration. In particular, mesenchymal stem cells have been widely exploited for this purpose, being multipotent cells capable of efficient osteogenic potential. Here we intend to review and update the alternative available techniques used for bone fusion, along with some hints on the advancements achieved through the experimental research in this field.

Background This meta-analysis aimed to determine the bone union rate of bone defects treated with the different autologous bone graft techniques. Methods The PubMed and the Cochrane Library databases were searched using the terms: ‘fracture’ AND (‘bone loss’ OR ‘defect’ OR ‘defects’) AND ‘bone graft’, restricted to English language, to human species, and to a publication period from January 1999 to November 2014. Data were extracted by one of the reviewers and then checked by the second. A quality of evidence score and a methodology score were used. Heterogeneity was assessed. A random effects model approach was used to combine estimates. Results Out of 376 selected studies only 34 met the inclusion criteria. The summary pooled union rate was 91 % (95 % CI: 87–95 %) while union rate after additional procedures raised to 98 % (95 % CI 96–99 %). No association between union rate and bone defect size was found. (Univariable regression model: vascularized: P  = 0.677; non-vascularized: 0.202. Multivariable regression model: vascularized: P  = 0.381; non-vascularized: P  = 0.226). Vascularized graft was associated with a lower risk of infection after surgery when compared to non-vascularized graft (95 % CI 0.03 to 0.23, p  < 0.001). Conclusion The results of this meta-analysis demonstrate the effectiveness of autologous graft for bone defects. Furthermore, from the available clinical evidence bone defect size does not seem to have an impact on bone union when treated with autologous bone graft techniques.

Vitoss is the most porous (90%) of a number of beta-tricalcium phosphate osteoconductive bone fillers. Its inherent limitations are those of the calcium phosphate class, being a purely osteoconductive product without inherent structural stability and with a moderate resorption rate. Currently, a number of additives, composites and related compounds are under study at various stages. In animal experiments, Vitoss performs well in comparison with other synthetic grafts, and with marrow added in various ways, it rivals autograft. Clinical efficacy is established for Vitoss as a spinal graft extender, as well as for periodontal, dental and orthopedic tumor defects. Apart from recombinant human platelet-derived growth factor, clinical data is lacking on the addition of bone marrow, stem cells and growth factors.

Autologous bone (AB) is the gold standard for bone-replacement surgeries 1 , despite its limited availability and the need for an extra surgical site. Traditionally, competitive biomaterials for bone repair have focused on mimicking the mineral aspect of bone, as evidenced by the widespread clinical use of bioactive ceramics 2 . However, AB also exhibits hierarchical organic structures that might substantially affect bone regeneration. Here, using a range of cell-free biomimetic-collagen-based materials in murine and ovine bone-defect models, we demonstrate that a hierarchical hybrid microstructure—specifically, the twisted plywood pattern of collagen and its association with poorly crystallized bioapatite—favourably influences bone regeneration. Our study shows that the most structurally biomimetic material has the potential to stimulate bone growth, highlighting the pivotal role of physicochemical properties in supporting bone formation and offering promising prospects as a competitive bone-graft material. By examining several cell-free biomimetic-collagen-based materials in murine and ovine bone-defect models, the twisted plywood pattern of collagen-based materials is shown to favourably influence bone regeneration and contributes to bone autograft performance.