Efficacy and safety of VEPTR instrumentation for progressive spine deformities in young children without rib fusions

This retrospective study analyses 23 children treated with vertical expandable prosthetic titanium rib (VEPTR) for correction of non-congenital early onset spine deformities. After the index procedure (IP), the device was lengthened at 6-month intervals. The average (av) age at the time of IP was 6.5years (1.11-10.5). The av follow-up time was 3.6years (2-5.8). Diagnosis included 1 early onset idiopathic scoliosis, 11 neuromuscular, 2 post-thoracotomy scoliosis, 1 Sprengel deformity, 2 hyperkyphosis, 1 myopathy and 5 syndromic. Surgeries (187) included 23 IPs, av 6.5 (4-10) device expansions per patient (149) and 15 unplanned surgeries. 23 complications (0.13 per surgery) included 10 skin sloughs, 5 implant dislocations, 2 rod breakages and 6 infections. Coronal Cobb angle was av 68° (11°-111°), at follow-up av 54° (0°-105°). Pelvic obliquity was av 33° (13°-60°), at follow-up av 16° (0°-42°). T1 tilt was av 29° (5°-84°), two remained unchanged, the remainder improved 10°-68°. Sagittal plane: All but two had stable profiles, two hyperkyphosis of 110°/124° improved to 56°/86°. Space available for lung ratio was less than 90% in ten before the IP, improved in nine and deteriorated in one. Originally designed for thoracic insufficiency syndromes related to rib and vertebral anomalies, VEPTR proved to be a valuable alternative to dual growing rods for non-congenital early onset spine deformities. The complication rate was lower, the control of the sagittal plane and the pelvic obliquity was as good, but the correction of the coronal plane deformity was less than growing rods. However, VEPTR's spine-sparing approach might provoke less spontaneous spinal fusion and ease the final correction at maturit

Effectiveness of the addition of Lidocaine to a hemostatic, bioresorbable putty in the treatment of iliac crest donor site pain

Background: The harvest of iliac crest bone grafts (ICBG) is associated with relevant donor site pain, but may be lowered by the application of lidocaine loaded on biodegradable, hemostatic putty for sustained local analgesic release. The goal of this double-blind controlled trial was to assess the efficacy of adding lidocaine to a hemostatic putty (Orthostat ™) to treat donor site pain following harvest of ICBG in foot and ankle procedures. Methods: After ICBG harvest during a foot and ankle procedure, the resulting bone defect was either filled with Orthostat™ (n = 7) or with the same hemostatic putty loaded with lidocaine (Orthostat-L™, n = 7). During the first 72 postoperative hours, donor site and surgical site pain were managed by patient controlled morphine delivery and a peripheral nerve block. Donor site pain was periodically quantified on a Visual Analog (VAS) and a Wong Baker FACES scale. Pain scores were plotted over time to calculate the area under the curve (AUC) to quantify the overall pain experienced in specific time intervals. Results: Orthostat-L™ significantly reduced donor site pain over the first 12 hours postoperatively as evidenced by a significant decrease of the AUC in both VAS (p = 0.0366) and Wong Baker FACES pain score plots (p = 0.0024). Cumulated morphine uses were not significantly decreased with Orthostat-L™. Conclusion: The addition of lidocaine to a hemostatic putty offers a significant ICBG donor site pain reduction over the first 12 postoperative hours. Trial registration ClinicalTrials.gov NCT01504035. Registered January 2nd 2012

Substitutes of Structural and Non-Structural Autologous Bone Grafts in Hindfoot Arthrodeses and Osteotomies: A Systematic Review

Background: Structural and non-structural substitutes of autologous bone grafts are frequently used in hindfoot arthrodeses and osteotomies. However, their efficacy is unclear. The primary goal of this systematic review was to compare autologous bone grafts with structural and non-structural substitutes regarding the odds of union in hindfoot arthrodeses and osteotomies. Methods: The Medline and EMBASE and Cochrane databases were searched for relevant randomized and non-randomized prospective studies as well as retrospective comparative chart reviews. Results: 10 studies which comprised 928 hindfoot arthrodeses and osteotomies met the inclusion criteria for this systematic review. The quality of the retrieved studies was low due to small samples sizes and confounding variables. The pooled random effect odds for union were 12.8 (95% CI 12.7 to 12.9) for structural allografts, 5.7 (95% CI 5.5 to 6.0) for cortical autologous grafts, 7.3 (95% CI 6.0 to 8.6) for cancellous allografts and 6.0 (95% CI 5.7 to 6.4) for cancellous autologous grafts. In individual studies, the odds of union in hindfoot arthrodeses achieved with cancellous autologous grafts was similar to those achieved with demineralised bone matrix or platelet derived growth factor augmented ceramic granules. Conclusion: Our results suggest an equivalent incorporation of structural allografts as compared to autologous grafts in hindfoot arthrodeses and osteotomies. There is a need for prospective randomized trials to further clarify the role of substitutes of autologous bone grafts in hindfoot surgery

Preoperative and Postoperative Factors and Laboratory Values Predicting Outcome in Patients Undergoing Lumbar Fusion Surgery

To determine whether complications in lumbar fusion surgery could be estimated from patient factors and perioperative laboratory values. In addition, risk scores for detection of patients prone to complications were defined. We retrospectively collected data of patients undergoing lumbar fusion surgery between 2013 and 2015. The patients were divided into group A (no complications) and group B (systemic and infectious complications within 30 days postoperatively). Patient-related factors and levels of perioperative laboratory values were compared between the groups and analyzed for possible impact on complications and length of stay (LOS) in the hospital. Data of 132 consecutive patients (74 women [56.1%]; median age, 68.5 years) were analyzed. Postoperative complications occurred in 29.5%. Higher postoperative creatine kinase (CK) and C-reactive protein and lower postoperative hemoglobin and thrombocyte values, as well as higher differences between preoperative and postoperative CK, C-reactive protein, and hemoglobin values were associated with postoperative complications. Among others, the combinations of advanced age and elevated body mass index (P = 0.0062, odds ratio: 3.018), or advanced age, elevated body mass index, and postoperative CK >166 U/L (P = 0.0016, odds ratio: 3.637) revealed patients with a threefold risk for complications. The combination of advanced age, American Society of Anesthesiologists score >2, and preoperative hemoglobin <12.9 g/dL was associated with a LOS of 20.3 versus 11 days (P = 0.01). Patients with postoperative complications and extended LOS seem to show significant differences in various perioperative laboratory values and patient factors. Perioperative risk assessments using cut-off values and risk scores may help identify patients prone to complications and extended resource use

Fibroblast growth factor-2 maintains a niche-dependent population of self-renewing highly potent non-adherent mesenchymal progenitors through FGFR2c

Bone marrow (BM) mesenchymal stem/stromal cells (MSC) are a heterogeneous population of multipotent progenitors currently under investigation for a variety of applications in regenerative medicine. While self-renewal of stem cells in different tissues has been demonstrated to be regulated by specialized microenvironments called niches, it is still unclear whether a self-renewing niche also exists for MSC. Here, we show that primary human BM cultures contain a population of intrinsically non-adherent mesenchymal progenitors (NAMP) with features of more primitive progenitors than the initially adhering colony-forming units-fibroblast (CFU-f). In fact, NAMP could generate an adherent progeny: (a) enriched with early mesenchymal populations (CD146+, SSEA-1+, and SSEA-4+); (b) with significantly greater proliferation and multilineage differentiation potential in vitro; and (c) capable of threefold greater bone formation in vivo than the corresponding CFU-f. Upon serial replating, NAMP were able to regenerate and expand in suspension as non-adherent clonogenic progenitors, while also giving rise to an adherent progeny. This took place at the cost of a gradual loss of proliferative potential, shown by a reduction in colony size, which could be completely prevented when NAMP were expanded on the initially adhering BM fraction. Mechanistically, we found that NAMP crucially depend on fibroblast growth factor (FGF)-2 signaling through FGFR2c for their survival and expansion. Furthermore, NAMP maintenance depends at least in part on humoral signals distinct from FGF-2. In conclusion, our data show a niche/progenitor organization in vitro, in which the BM adherent fraction provides a self-renewing microenvironment for primitive NAMP

Engineering of large osteogenic grafts with rapid engraftment capacity using mesenchymal and endothelial progenitors from human adipose tissue

We investigated whether the maintenance in culture of endothelial and mesenchymal progenitors from the stromal vascular fraction (SVF) of human adipose tissue supports the formation of vascular structures in vitro and thereby improves the efficiency and uniformity of bone tissue formation in vivo within critically sized scaffolds. Freshly-isolated human SVF cells were seeded and cultured into hydroxyapatite scaffolds (1 cm-diameter, 1 cm-thickness) using a perfusion-based bioreactor system, which resulted in maintenance of CD34(+)/CD31(+) endothelial lineage cells. Monolayer-expanded isogenic adipose stromal cells (ASC) and age-matched bone marrow stromal cells (BMSC), both lacking vasculogenic cells, were used as controls. After 5 days in vitro, SVF-derived endothelial and mesenchymal progenitors formed capillary networks, which anastomosed with the host vasculature already 1 week after ectopic nude rat implantation. As compared to BMSC and ASC, SVF-derived cells promoted faster tissue ingrowth, more abundant and uniform bone tissue formation, with ossicles reaching a 3.5 mm depth from the scaffold periphery after 8 weeks. Our findings demonstrate that maintenance of endothelial/mesenchymal SVF cell fractions is crucial to generate osteogenic constructs with enhanced engraftment capacity. The single, easily accessible cell source and streamlined, bioreactor-based process makes the approach attractive towards manufacturing of clinically relevant sized bone substitute grafts

Intervertebral Disc-on-a-Chip as Advanced In Vitro Model for Mechanobiology Research and Drug Testing: A Review and Perspective

Discogenic back pain is one of the most diffused musculoskeletal pathologies and a hurdle to a good quality of life for millions of people. Existing therapeutic options are exclusively directed at reducing symptoms, not at targeting the underlying, still poorly understood, degenerative processes. Common intervertebral disc (IVD) disease models still do not fully replicate the course of degenerative IVD disease. Advanced disease models that incorporate mechanical loading are needed to investigate pathological causes and processes, as well as to identify therapeutic targets. Organs-on-chip (OoC) are microfluidic-based devices that aim at recapitulating tissue functions in vitro by introducing key features of the tissue microenvironment (e.g., 3D architecture, soluble signals and mechanical conditioning). In this review we analyze and depict existing OoC platforms used to investigate pathological alterations of IVD cells/tissues and discuss their benefits and limitations. Starting from the consideration that mechanobiology plays a pivotal role in both IVD homeostasis and degeneration, we then focus on OoC settings enabling to recapitulate physiological or aberrant mechanical loading, in conjunction with other relevant features (such as inflammation). Finally, we propose our view on design criteria for IVD-on-a-chip systems, offering a future perspective to model IVD mechanobiology

A Single Injection of NTG-101 Reduces the Expression of Pain-Related Neurotrophins in a Canine Model of Degenerative Disc Disease

Background: Tissue sources of pain emanating from degenerative discs remains incompletely understood. Canine intervertebral discs (IVDs) were needle puncture injured, 4-weeks later injected with either phosphate-buffered saline (PBS) or NTG-101, harvested after an additional fourteen weeks and then histologically evaluated for the expression of NGFr, BDNF, TrkB and CALCRL proteins. Quantification was performed using the HALO automated cell-counting scoring platform. Immunohistochemical analysis was also performed on human IVD tissue samples obtained from spinal surgery. Immunohistochemical analysis and quantification of neurotrophins and neuropeptides was performed using an in vivo canine model of degenerative disc disease and human degenerative disc tissue sections. Discs injected with NTG-101 showed significantly lower levels of Nerve Growth Factor receptor (NGFr/TrkA, p = 0.0001), BDNF (p = 0.009), TrkB (p = 0.002) and CALCRL (p = 0.008) relative to PBS injections. Human IVD tissue obtained from spinal surgery due to painful DDD show robust expression of NGFr, BDNF, TrkB and CALCRL proteins. A single intradiscal injection of NTG-101 significantly inhibits the expression of NGFr, BDNF, TrkB and CALCRL proteins in degenerative canine IVDs. These results strongly suggest that NTG-101 inhibits the development of neurotrophins that are strongly associated with painful degenerative disc disease and may have profound effects upon the management of patients living with discogenic pain