National Football League Head, Neck and Spine Committee's Concussion Diagnosis and Management Protocol: 2017-18 season.

One of the National Football League's (NFL) Head, Neck and Spine Committee's principal goals is to create a 'best practice' protocol for concussion diagnosis and management for its players. The science related to concussion diagnosis and management continues to evolve, thus the protocol has evolved contemporaneously. The Fifth International Conference on Concussion in Sport was held in Berlin in 2016, and guidelines for sports concussion diagnosis and management were revised and refined. The NFL Head, Neck and Spine Committee has synthesised the most recent empirical evidence for sports concussion diagnosis and management including the Berlin consensus statement and tailored it to the game played in the NFL. One of the goals of the Committee is to provide a standardised, reliable, efficient and evidence-based protocol for concussion diagnosis and management that can be applied in this professional sport during practice and game day. In this article, the end-of-season version of the 2017-18 NFL Concussion Diagnosis and Management Protocol is described along with its clinical rationale. Immediate actions for concussion programme enhancement and research are reviewed. It is the Committee's expectation that the protocol will undergo refinement and revision over time as the science and clinical practice related to concussion in sports crystallise.

A Mechanistic and Preclinical Assessment of BioRestore Bioactive Glass as a Synthetic Bone Graft Extender and Substitute for Osteoinduction and Spine Fusion.

STUDY DESIGN: Preclinical animal study. OBJECTIVE: Evaluate the osteoinductivity and bone regenerative capacity of BioRestore bioactive glass. SUMMARY OF BACKGROUND DATA: BioRestore is a Food and Drug Administration (FDA)-approved bone void filler that has not yet been evaluated as a bone graft extender or substitute for spine fusion. METHODS: In vitro and in vivo methods were used to compare BioRestore with other biomaterials for the capacity to promote osteodifferentiation and spinal fusion. The materials evaluated (1) absorbable collagen sponge (ACS), (2) allograft, (3) BioRestore, (4) Human Demineralized Bone Matrix (DBM), and (5) MasterGraft. For in vitro studies, rat bone marrow-derived stem cells (BMSC) were cultured on the materials in either standard or osteogenic media (SM, OM), followed by quantification of osteogenic marker genes ( Runx2, Osx, Alpl, Bglap, Spp1 ) and alkaline phosphatase (ALP) activity. Sixty female Fischer rats underwent L4-5 posterolateral fusion (PLF) with placement of 1 of 5 implants: (1) ICBG from syngeneic rats; (2) ICBG+BioRestore; (3) BioRestore alone; (4) ICBG+Allograft; or (5) ICBG+MasterGraft. Spines were harvested 8 weeks postoperatively and evaluated for bone formation and fusion via radiography, blinded manual palpation, microCT, and histology. RESULTS: After culture for 1 week, BioRestore promoted similar expression levels of Runx2 and Osx to cells grown on DBM. At the 2-week timepoint, the relative ALP activity for BioRestore-OM was significantly higher ( P <0.001) than that of ACS-OM and DBM-OM ( P <0.01) and statistically equivalent to cells grown on allograft-OM. In vivo, radiographic and microCT evaluation showed some degree of bridging bone formation in all groups tested, with the exception of BioRestore alone, which did not produce successful fusions. CONCLUSIONS: This study demonstrates the capacity of BioRestore to promote osteoinductivity in vitro. In vivo, BioRestore performed similarly to commercially available bone graft extender materials but was incapable of producing fusion as a bone graft substitute. LEVEL OF EVIDENCE: Level V.

A supramolecular polymer-collagen microparticle slurry for bone regeneration with minimal growth factor.

Recombinant bone morphogenetic protein-2 (BMP-2) is a potent osteoinductive growth factor that can promote bone regeneration for challenging skeletal repair and even for ectopic bone formation in spinal fusion procedures. However, serious clinical side effects related to supraphysiological dosing highlight the need for advances in novel biomaterials that can significantly reduce the amount of this biologic. Novel biomaterials could not only reduce clinical side effects but also expand the indications for use of BMP-2, while at the same time lowering the cost of such procedures. To achieve this objective, we have developed a slurry containing a known supramolecular polymer that potentiates BMP-2 signaling and porous collagen microparticles. This slurry exhibits a paste-like consistency that stiffens into an elastic gel upon implantation making it ideal for minimally invasive procedures. We carried out in vivo evaluation of the novel biomaterial in the rabbit posterolateral spine fusion model, and discovered efficacy at unprecedented ultra-low BMP-2 doses (5 µg/implant). This dose reduces the growth factor requirement by more than 100-fold relative to current clinical products. This observation is significant given that spinal fusion involves ectopic bone formation and the rabbit model is known to be predictive of human efficacy. We expect the novel biomaterial can expand BMP-2 indications for difficult cases requiring large volumes of bone formation or involving patients with underlying conditions that compromise bone regeneration.

Odontoid fractures: update on management.

Recognition of the incidence of odontoid fractures as well as the associated morbidity and unexpectedly high mortality rates has prompted significant changes in the management of these fractures in the past decade. Nonsurgical management of type II odontoid fracture has historically been associated with a high nonunion rate. Thus, new classification systems have been devised to identify patients who might benefit from early surgical treatment. The decision-making process is particularly difficult when treating elderly patients. Increased familiarity with anterior and posterior surgical techniques has led to more aggressive treatment of odontoid fracture, with the intent of hastening functional rehabilitation. However, these clinical decisions have been associated with a significant rate of complications. The treatment algorithm for odontoid fractures continues to evolve based on the improved understanding of, and evidence-based literature on, anterior screw fixation, posterior spinal fusion, and halo-vest immobilization.

Bone void fillers.

For this technology overview, the tools of evidence-based medicine were used to summarize information on the effectiveness and clinical outcomes related to the usage of bone void fillers- specifically, synthetic graft materials. Comprehensive literature searches were conducted to address five key questions, which the task force that prepared the report posed as follows. Question 1 addressed the use of synthetic bone void fillers alone. Question 2 was designed to determine whether synthetic bone void fillers could successfully serve as graft extenders and eliminate the need for iliac crest bone graft. Questions 3, 4, and 5 addressed the use of allografts as a comparison with synthetic fillers because clinical results with allografts are perceived as being much closer to autografts in these areas of the spine.

3D-Printed Ceramic-Demineralized Bone Matrix Hyperelastic Bone Composite Scaffolds for Spinal Fusion.

Although numerous spinal biologics are commercially available, a cost-effective and safe bone graft substitute material for spine fusion has yet to be proven. In this study, "3D-Paints" containing varying volumetric ratios of hydroxyapatite (HA) and human demineralized bone matrix (DBM) in a poly(lactide-co-glycolide) elastomer were three-dimensional (3D) printed into scaffolds to promote osteointegration in rats, with an end goal of spine fusion without the need for recombinant growth factor. Spine fusion was evaluated by manual palpation, and osteointegration and de novo bone formation within scaffold struts were evaluated by laboratory and synchrotron microcomputed tomography and histology. The 3:1 HA:DBM composite achieved the highest mean fusion score and fusion rate (92%), which was significantly greater than the 3D printed DBM-only scaffold (42%). New bone was identified extending from the host transverse processes into the scaffold macropores, and osteointegration scores correlated with successful fusion. Strikingly, the combination of HA and DBM resulted in the growth of bone-like spicules within the DBM particles inside scaffold struts. These spicules were not observed in DBM-only scaffolds, suggesting that de novo spicule formation requires both HA and DBM. Collectively, our work suggests that this recombinant growth factor-free composite shows promise to overcome the limitations of currently used bone graft substitutes for spine fusion. Impact Statement Currently, there exists a no safe, yet highly effective, bone graft substitute that is well accepted for use in spine fusion procedures. With this work, we show that a three-dimensional printed scaffold containing osteoconductive hydroxyapatite and osteoinductive demineralized bone matrix that promotes new bone spicule formation, osteointegration, and successful fusion (stabilization) when implemented in a preclinical model of spine fusion. Our study suggests that this material shows promise as a recombinant growth factor-free bone graft substitute that could safely promote high rates of successful fusion and improve patient care.

Consensus Recommendations on the Prehospital Care of the Injured Athlete With a Suspected Catastrophic Cervical Spine Injury.

INTRODUCTION: Sports participation is among the leading causes of catastrophic cervical spine injury (CSI) in the United States. Appropriate prehospital care for athletes with suspected CSIs should be available at all levels of sport. The goal of this project was to develop a set of best-practice recommendations appropriate for athletic trainers, emergency responders, sports medicine and emergency physicians, and others engaged in caring for athletes with suspected CSIs. METHODS: A consensus-driven approach (RAND/UCLA method) in combination with a systematic review of the available literature was used to identify key research questions and develop conclusions and recommendations on the prehospital care of the spine-injured athlete. A diverse panel of experts, including members of the National Athletic Trainers' Association, the National Collegiate Athletic Association, and the Sports Institute at UW Medicine participated in 4 Delphi rounds and a 2-day nominal group technique meeting. The systematic review involved 2 independent reviewers and 4 rounds of blinded review. RESULTS: The Delphi process identified 8 key questions to be answered by the systematic review. The systematic review comprised 1544 studies, 49 of which were included in the final full-text review. Using the results of the systematic review as a shared evidence base, the nominal group technique meeting created and refined conclusions and recommendations until consensus was achieved. CONCLUSIONS: These conclusions and recommendations represent a pragmatic approach, balancing expert experiences and the available scientific evidence.

Bony ingrowth potential of 3D-printed porous titanium alloy: a direct comparison of interbody cage materials in an in vivo ovine lumbar fusion model.

BACKGROUND CONTEXT: There is significant variability in the materials commonly used for interbody cages in spine surgery. It is theorized that three-dimensional (3D)-printed interbody cages using porous titanium material can provide more consistent bone ingrowth and biological fixation. PURPOSE: The purpose of this study was to provide an evidence-based approach to decision-making regarding interbody materials for spinal fusion. STUDY DESIGN: A comparative animal study was performed. METHODS: A skeletally mature ovine lumbar fusion model was used for this study. Interbody fusions were performed at L2-L3 and L4-L5 in 27 mature sheep using three different interbody cages (ie, polyetheretherketone [PEEK], plasma sprayed porous titanium-coated PEEK [PSP], and 3D-printed porous titanium alloy cage [PTA]). Non-destructive kinematic testing was performed in the three primary directions of motion. The specimens were then analyzed using micro-computed tomography (µ-CT); quantitative measures of the bony fusion were performed. Histomorphometric analyses were also performed in the sagittal plane through the interbody device. Outcome parameters were compared between cage designs and time points. RESULTS: Flexion-extension range of motion (ROM) was statistically reduced for the PTA group compared with the PEEK cages at 16 weeks (p-value=.02). Only the PTA cages demonstrated a statistically significant decrease in ROM and increase in stiffness across all three loading directions between the 8-week and 16-week sacrifice time points (p-value≤.01). Micro-CT data demonstrated significantly greater total bone volume within the graft window for the PTA cages at both 8 weeks and 16 weeks compared with the PEEK cages (p-value<.01). CONCLUSIONS: A direct comparison of interbody implants demonstrates significant and measurable differences in biomechanical, µ-CT, and histologic performance in an ovine model. The 3D-printed porous titanium interbody cage resulted in statistically significant reductions in ROM, increases in the bone ingrowth profile, as well as average construct stiffness compared with PEEK and PSP.

Novel Osteobiologics and Biomaterials in the Treatment of Spinal Disorders.

Spinal osteobiologics have evolved substantially in this century after the development of many product categories such as growth factors, allograft, and stem cells. The indications for the use of novel biologics within spine surgery are rapidly expanding as the mechanism of each is elucidated. While the knowledge base of bone morphogenetic protein increases with each subsequent year, the application of new nanotechnology and cell-based strategies are being reported. This review will discuss the most recent data in novel osteobiologics, and where we could use future study.

Demineralized bone matrix fibers formable as general and custom 3D printed mold-based implants for promoting bone regeneration.

INTRODUCTION: Bone repair frequently requires time-consuming implant construction, particularly when using un-formed implants with poor handling properties. We therefore developed osteoinductive, micro-fibrous surface patterned demineralized bone matrix (DBM) fibers for engineering both defect-matched and general three-dimensional implants. METHODS AND RESULTS: Implant molds were filled with demineralized human cortical bone fibers there were compressed and lyophilized, forming mechanically strong shaped DBM scaffolds. Enzyme linked immunosorbent assays and mass spectrometry confirmed that DBM fibers contained abundant osteogenic growth factors (bone morphogenetic proteins, insulin-like growth factor-I) and extracellular matrix proteins. Mercury porosimetry and mechanical testing showed interconnected pores within the mechanically stable, custom DBM fiber scaffolds. Mesenchymal stem cells readily attached to the DBM and showed increasing metabolic activity over time. DBM fibers further increased alkaline phosphatase activity in C2C12 cells. In vivo, DBM implants elicited osteoinductive potential in a mouse muscle pouch, and also promoted spine fusion in a rat arthrodesis model. SIGNIFICANCE: DBM fibers can be engineered into custom-shaped, osteoinductive and osteoconductive implants with potential for repairing osseous defects with precise fitment, potentially reducing operating time. By providing pre-formed and custom implants, this regenerative allograft may improve patient outcomes following surgical bone repair, while further advancing personalized orthopedic and craniomaxillofacial medicine using three-dimensional-printed tissue molds.

Hyperelastic "bone": A highly versatile, growth factor-free, osteoregenerative, scalable, and surgically friendly biomaterial.

Despite substantial attention given to the development of osteoregenerative biomaterials, severe deficiencies remain in current products. These limitations include an inability to adequately, rapidly, and reproducibly regenerate new bone; high costs and limited manufacturing capacity; and lack of surgical ease of handling. To address these shortcomings, we generated a new, synthetic osteoregenerative biomaterial, hyperelastic "bone" (HB). HB, which is composed of 90 weight % (wt %) hydroxyapatite and 10 wt % polycaprolactone or poly(lactic-co-glycolic acid), could be rapidly three-dimensionally (3D) printed (up to 275 cm(3)/hour) from room temperature extruded liquid inks. The resulting 3D-printed HB exhibited elastic mechanical properties (~32 to 67% strain to failure, ~4 to 11 MPa elastic modulus), was highly absorbent (50% material porosity), supported cell viability and proliferation, and induced osteogenic differentiation of bone marrow-derived human mesenchymal stem cells cultured in vitro over 4 weeks without any osteo-inducing factors in the medium. We evaluated HB in vivo in a mouse subcutaneous implant model for material biocompatibility (7 and 35 days), in a rat posterolateral spinal fusion model for new bone formation (8 weeks), and in a large, non-human primate calvarial defect case study (4 weeks). HB did not elicit a negative immune response, became vascularized, quickly integrated with surrounding tissues, and rapidly ossified and supported new bone growth without the need for added biological factors.

Biological substitutes/extenders for spinal arthrodesis: which agents are cost-effective?

STUDY DESIGN: Systematic review. OBJECTIVE: To evaluate the cost-effectiveness of lumbar or cervical spinal arthrodesis using biological substitutes and extenders compared with iliac crest autograft for the treatment of degenerative spinal conditions. SUMMARY OF BACKGROUND DATA: The cost-effectiveness of using bone graft substitutes and extenders for spinal fusion compared with using iliac crest autograft is not yet well established. METHODS: A systematic search of PubMed/MEDLINE, the Cochrane Collaboration Library, EMBASE, the CRD (Centre for Reviews and Dissemination) database, and Tuft's CEA registry for literature published through December 2013 was performed to identify full formal economic analyses comparing the use of biological grafts with iliac crest bone graft in spinal fusion for thoracolumbar or cervical degenerative, deformity, and traumatic spinal conditions. Economic outcomes such as cost per improved outcome or cost per quality-adjusted life year were reported in the context of the model type, analytic perspective clinical comparisons, and sensitivity analyses employed. RESULTS: The search strategy yielded 88 citations, and 6 full economic analyses ultimately met our inclusion criteria. For the comparison of recombinant human bone morphogenetic protein-2 to iliac crest bone graft in the lumbar spine, data from 4 cost-effectiveness studies and 1 cost-utility study provided discordant conclusions that varied with type of data used, cost-measurement methods, and study design. In the cervical spine, one study suggested that from a societal perspective, anterior cervical discectomy and fusion (ACDF) with allograft is similarly cost-effective as ACDF with autograft. CONCLUSION: The results suggest that compared with use of iliac crest bone graft in lumbar spinal fusion, use of recombinant human bone morphogenetic protein is not cost-effective from a payer perspective with higher upfront costs, but it may be cost-effective from a societal perspective due to a decrease in lost productivity. The data in this study also suggest that from a societal perspective, ACDF with allograft is similarly cost-effective to ACDF with autograft. LEVEL OF EVIDENCE: 3.

Nanocomposite therapy as a more efficacious and less inflammatory alternative to bone morphogenetic protein-2 in a rodent arthrodesis model.

The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in spine fusion has led to concerns regarding a potential accompanying inflammatory response. This study evaluates a combination therapy (TrioMatrix®; Pioneer Surgical, Inc., Marquette, MI) comprised of a demineralized bone matrix (DBM), hydroxyapatite, and a nanofiber-based collagen scaffold in a rodent spine fusion model. Thirty-six athymic rats that underwent a posterolateral intertransverse spinal fusion were randomly assigned to 1 of 5 treatment groups: absorbable collagen sponge alone (ACS, negative control), 10 µg rhBMP-2 on ACS (positive control), TrioMatrix®, Grafton® (Osteotech, Inc., Eatontown, NJ), and DBX® (Synthes, Inc., West Chester, PA). Both TrioMatrix® and rhBMP-2-treated animals demonstrated 100% fusion rates as graded by manual palpation scores 8 weeks after implantation. This rate was significantly greater than those of the ACS, Grafton®, and DBX® groups. Notably, the use of TrioMatrix® as evaluated by microCT quantification led to a greater fusion mass volume when compared to all other groups, including the rhBMP-2 group. T2-weighted axial MRI images of the fusion bed demonstrated a significant host response associated with a large fluid collection with the use of rhBMP-2; this response was significantly reduced with the use of TrioMatrix®. Our results therefore demonstrate that a nanocomposite therapy represents a promising, cost-effective bone graft substitute that could be useful in spine fusions where BMP-2 is contraindicated.