Development of a sacral fracture model to demonstrate effects on sagittal alignment.

PURPOSE: To develop a modeling framework to predict the secondary consequences on spinal alignment following correction and to demonstrate the impact of pedicle subtraction osteotomy (PSO) location on sagittal alignment. METHODS: Six patients were included, and pelvic incidence (PI) was measured. Full-length standing radiographs were uploaded into PowerPoint and manipulated to model S1-S2 joint line sacral fractures at 15°, 20°, 25°, and 30°. PSO corrections with hinge points at the anterior superior corner and vertical midpoint of the L3-5 vertebral bodies were modeled. Anterior translation (AT) and vertical shortening (VS) were calculated for the six PSO locations in the four fracture angle (FA) models. RESULTS: PI had a strong effect in the mixed AT and VS models (P < 0.001). Both AT and VS were significantly different from zero at all FA (p < 0.001), and pairwise comparisons revealed all FA were different from each other with respect to both AT and VS after adjusting for PSO location (p < 0.001), increasing as FA increased. Varying PSO location resulted in significant differences in AT when comparing all locations (p < 0.001). AT was greatest for all FA in all patients when the PSO correction was performed at the L3-AS (p < 0.001). There were significant differences in VS when comparing the L5-Mid PSO location to the L3-AS, L3-Mid, L4-AS, and L4-Mid PSO locations (p < 0.034). CONCLUSION: PSO correction superior to a sacral fracture resulted in AT and VS of the spine. It is crucial that these changes in spinal measures be predicted and accounted for to optimize patient sagittal alignment and outcomes.

MCL internal brace does not fully recapitulate normal MCL function in valgus stress.

PURPOSE: The null hypothesis is that there would be no difference in medial gapping under valgus load between the intact MCL and the ruptured MCL with an internal brace in place. METHODS: Eight pairs of cadaver knees were used (16 knees). Alternating sides, one knee from each pair was used for one of two "internal brace" constructs. The constructs involved different methods of fixation for securing FiberTape (Arthrex, Naples, FL) to both the femur and tibia in an effort to brace the MCL. The knees were then subjected to valgus stress by applying 10 N m of torque with the knee at 20 degrees of flexion. The amount of medial joint space opening was measured on radiographs. The stress testing was conducted with three MCL states: intact, grade 2 tear, and grade 3 tear. RESULTS: In the Construct I specimens, gapping increased from 0.7 mm with the MCL intact to 1.1 mm with grade 2 tearing (p < 0.01), and to 1.3 mm with grade 3 tearing (p < 0.01). In the Construct II specimens, gapping increased from 0.7 mm with the MCL intact to 1.0 mm with grade 2 tearing (p < 0.01), and to 1.1 mm with grade 3 tearing (n.s.). Construct I specimens failed primarily at the femoral attachment. All Construct II specimens survived the valgus stress testing. CONCLUSION: Construct I did not maintain tension. Construct II did maintain tension during application of valgus load, but did not restore valgus opening to the intact state. It is important for clinicians who are considering using this commercially available technique to be aware of how the construct performs under valgus stress testing compared to the intact MCL.

An MCL internal brace can withstand cyclic fatigue loading and produce a valgus load to failure similar to that of intact knees.

PURPOSE: The purpose of this study is to report on the biomechanical durability and strength of an MCL internal brace construct. The null hypothesis is that there will be no difference between this construct and the intact MCL in terms of deflection during fatigue testing and the ultimate failure load. METHODS: Eight cadaver knees were used. A grade 3 equivalent MCL tear was created with both the superficial and deep femoral MCL severed. An internal brace was created by placing a cortical button and loop through the center of the femoral MCL origin and secured on the lateral cortex of the distal femur. A FiberTape (Arthrex, Naples, FL) was looped through the cortical button loop and was secured in the center of the tibial insertion of the MCL. After pre-cycling, the specimens underwent 1000 cycles of compressive load between 100 and 300 N, using four point bending testing into direct valgus. Pre and post testing deflection was measured using three dimensional motion data from two sets of reflective markers. A load-to-failure test was then conducted with failure defined as the first significant decrease in the load-displacement curve. RESULTS: The mean increase in deflection between pre- and post-testing was 0.6° (SD ± 0.3°). The mean failure bending moment was 122.4 Nm (SD ± 29 Nm). CONCLUSION: The internal brace construct employed in this study was able to withstand cyclic fatigue loading and recorded a valgus load to failure similar to that of intact knees. It is important for clinicians who are considering using this commercially available technique to be aware of how the construct performs under cyclic loading compared to the intact MCL.

Culture and characterization of various porcine integumentary-connective tissue-derived mesenchymal stromal cells to facilitate tissue adhesion to percutaneous metal implants.

BACKGROUND: Transdermal osseointegrated prosthesis have relatively high infection rates leading to implant revision or failure. A principle cause for this complication is the absence of a durable impervious biomechanical seal at the interface of the hard structure (implant) and adjacent soft tissues. This study explores the possibility of recapitulating an analogous cellular musculoskeletal-connective tissue interface, which is present at naturally occurring integumentary tissues where a hard structure exits the skin, such as the nail bed, hoof, and tooth. METHODS: Porcine mesenchymal stromal cells (pMSCs) were derived from nine different porcine integumentary and connective tissues: hoof-associated superficial flexor tendon, molar-associated periodontal ligament, Achilles tendon, adipose tissue and skin dermis from the hind limb and abdominal regions, bone marrow and muscle. For all nine pMSCs, the phenotype, multi-lineage differentiation potential and their adhesiveness to clinical grade titanium was characterized. Transcriptomic analysis of 11 common genes encoding cytoskeletal proteins VIM (Vimentin), cell-cell and cell-matrix adhesion genes (Vinculin, Integrin ß1, Integrin ß2, CD9, CD151), and for ECM genes (Collagen-1a1, Collagen-4a1, Fibronectin, Laminin-α5, Contactin-3) in early passaged cells was performed using qRT-PCR. RESULTS: All tissue-derived pMSCs were characterized as mesenchymal origin by adherence to plastic, expression of cell surface markers including CD29, CD44, CD90, and CD105, and lack of hematopoietic (CD11b) and endothelial (CD31) markers. All pMSCs differentiated into osteoblasts, adipocytes and chondrocytes, albeit at varying degrees, under specific culture conditions. Among the eleven adhesion genes evaluated, the cytoskeletal intermediate filament vimentin was found highly expressed in pMSC isolated from all tissues, followed by genes for the extracellular matrix proteins Fibronectin and Collagen-1a1. Expression of Vimentin was the highest in Achilles tendon, while Fibronectin and Col1agen-1a1 were highest in molar and hoof-associated superficial flexor tendon bone marrow, respectively. Achilles tendon ranked the highest in both multilineage differentiation and adhesion assessments to titanium metal. CONCLUSIONS: These findings support further preclinical research of these tissue specific-derived MSCs in vivo in a transdermal osseointegration implant model.

Biomechanical Stability of the Sacroiliac Joint with Differing Implant Configurations in a Synthetic Model.

BACKGROUND: The sacroiliac joint (SIJ) is responsible for 15%-30% of chronic low back pain and fusion is increasingly used to alleviate chronic SIJ pain in adults. However, questions remain as to the most effective implant patterns to stabilize the joint. The objective of this biomechanical study was to evaluate how different implant spacing, configuration and quantity effect range of motion (ROM) of a synthetic foam SIJ model. METHODS: Triangular SIJ fusion implants were tested in six patterns using three implants, and two patterns with two implants (n = 5/pattern). Linear, triangular, and angled (10° or 20°) implant patterns were used with spacing of 13 or 22 mm between implants. Implants were placed through a denser polyurethane foam block (0.32 g/cm3) representing the ilium and into a less dense block representing the sacrum (0.16 g/cm3) to a depth 30 mm with a 2-mm gap between blocks. Cyclic torsion and shear testing were conducted for 10,000 cycles and ROM was recorded. Pullout testing was conducted on non-cycled (n = 10) implants and individually on all implants after construct cycling. RESULTS: ROM was significantly lower for all 22-mm implant patterns compared to the 13 mm linear pattern after cyclic loading in both torsion and shear. The use of three implants provided 60% and 86% greater stability, respectively, than two implants with spacing of 22 and 13 mm. Pullout resistance followed similar trends with the lowest forces occurring in closely spaced patterns that used two implants. CONCLUSIONS: This study demonstrated that the use of three implants and maximizing the spacing between implants might provide greater stability to the SIJ. If implants must be placed closely, then nonlinear patterns may improve construct stability.

Augmentation of implant surfaces with BMP-2 in a revision setting : effects of local and systemic bisphosphonate.

AIMS: We wanted to evaluate the effects of a bone anabolic agent (bone morphogenetic protein 2 (BMP-2)) on an anti-catabolic background (systemic or local zoledronate) on fixation of allografted revision implants. METHODS: An established allografted revision protocol was implemented bilaterally into the stifle joints of 24 canines. At revision surgery, each animal received one BMP-2 (5 µg) functionalized implant, and one raw implant. One group (12 animals) received bone graft impregnated with zoledronate (0.005 mg/ml) before impaction. The other group (12 animals) received untreated bone graft and systemic zoledronate (0.1 mg/kg) ten and 20 days after revision surgery. Animals were observed for an additional four weeks before euthanasia. RESULTS: No difference was detected on mechanical implant fixation (load to failure, stiffness, energy) between local or systemic zoledronate. Addition of BMP-2 had no effect on implant fixation. In the histomorphometric evaluation, implants with local zoledronate had more area of new bone on the implant surface (53%, p = 0.025) and higher volume of allograft (65%, p = 0.007), whereas implants in animals with systemic zoledronate had the highest volume of new bone (34%, p = 0.003). Systemic zoledronate with BMP-2 decreased volume of allograft by 47% (p = 0.017). CONCLUSION: Local and systemic zoledronate treatment protects bone at different stages of maturity; local zoledronate protects the allograft from resorption and systemic zoledronate protects newly formed bone from resorption. BMP-2 in the dose evaluated with experimental revision implants was not beneficial, since it significantly increased allograft resorption without a significant compensating anabolic effect. Cite this article: Bone Joint Res 2021;10(8):488-497.

A Vision for Using Simulation & Virtual Coaching to Improve the Community Practice of Orthopedic Trauma Surgery.

Background: Many orthopedic surgeries involve the challenging integration of fluoroscopic image interpretation with skillful tool manipulation to enable procedures to be performed through less invasive approaches. Simulation has proved beneficial for teaching and improving these skills for residents, but similar benefits have not yet been realized for practicing orthopedic surgeons. A vision is presented to elevate community orthopedic practice and improve patient safety by advancing the use of simulators for training and assessing surgical skills. Methods: Key elements of this vision that are established include 1) methods for the objective and rigorous assessment of the performance of practicing surgeons now exist, 2) simulators are sufficiently mature and sophisticated that practicing surgeons will use them, and 3) practicing surgeons can improve their performance with appropriate feedback and coaching. Results: Data presented indicate that surgical performance can be adequately and comparably measured using structured observations made by experts or non-expert crowds, with the crowdsourcing approach being more expedient and less expensive. Rigorous measures of the surgical result and intermediate objectives obtained semi-automatically from intra-operative fluoroscopic image sequences can distinguish performances of experts from novices. Experience suggests that practicing orthopedic surgeons are open to and can be constructively engaged by a family of mature simulators as a means to evaluate and improve their surgical skills. Conclusions: The results presented support our contention that new objective assessment measures are sufficient for evaluating the performance of working surgeons. The novel class of orthopedic surgical simulators available were tested and approved by practicing physicians. There exists a clear opportunity to combine purpose-designed simulator exercises with virtual coaching to help practicing physicians retain, retrain, and improve their technical skills. This will ultimately reduce cost, increase the quality of care, and decrease complication rates. Clinical Relevance: This vision articulates a means to boost the confidence of practitioners and ease their anxiety so that they perform impactful procedures more often in community hospitals, which promises to improve treatment and reduce the cost of care while keeping patients closer to their homes and families.

Compartment Syndrome: Evaluation of Skeletal Muscle Ischemia and Physiologic Biomarkers in Controlled Conditions Within Ex Vivo Isolated Muscle Bundles.

OBJECTIVES: To identify potential physiologic markers of muscle ischemia to serve as diagnostic indicators of compartment syndrome. We hypothesize that muscle bundles in hypoxic conditions will elicit decreases in potential hydrogen (pH) and increases in lactate and potassium that correlates with decreased muscle twitch forces. METHODS: We performed an ex vivo evaluation of individual skeletal muscle bundles obtained from a swine's diaphragm that were exposed to hypoxic conditions and compared with control groups. Over a 4-hour period, we evaluated the following parameters for each muscle bundle: muscle twitch forces and levels of potassium, lactate, and pH. Comparisons between the hypoxic and control groups were calculated at each time point using the 2-tailed Wilcoxon rank sum test for nonparametric data. Longitudinal associations between biomarkers and muscle twitch forces were tested using repeated measures analyses. RESULTS: The hypoxic group elicited more significant decreases in normalized muscle twitch forces than the control group at all time points (0.15 g vs. 0.55 g at 4 hours, P < 0.001). Repeated measures analyses of the hypoxic group demonstrated a statistically significant association between potassium, lactate, and normalized peak force over the course of time. Potassium demonstrated the strongest association with a 1 mmol/L unit increase in potassium associated with a 2.9 g decrease in normalized peak force (95% confidence interval -3.3 to -2.4, P < 0.001). The pH of all muscle baths increased over the course of time at similar rates between the study groups. CONCLUSIONS: This study used an ex vivo ischemic skeletal muscle model as a representation for pathophysiologic pathways associated with compartment syndrome. In this experimental approach we were unable to evaluate the pH of the muscle bundles due to continuous applied gassing. Our findings support further evaluations of potassium and lactate levels as potential diagnostic markers.

Orthopaedic osseointegration: Implantology and future directions.

Osseointegration (OI) is the direct anchorage of a metal implant into bone, allowing for the connection of an external prosthesis to the skeleton. Osseointegration was first discovered in the 1960s based on the microscopic analysis of titanium implant placed into host bone. New bone was observed to attach directly to the metal surface. Following clinical investigations into dentistry applications, OI was adapted to treat extremity amputations. These bone anchored implants, which penetrate the skin and soft tissues, eliminate many of the challenges of conventional prosthetic sockets, such as poor fit and suspension, skin breakdown, and pain. Osseointegrated implants show promise to improve prosthesis use, pain, and function for amputees. The successful process of transcutaneous metal integration into host bone requires three synergistic systems: the host bone, the metal implant, and the skin-implant interface. All three systems must be optimized for successful incorporation and longevity of the implant. Osseointegration begins during surgical implantation of the metal components through a complex interplay of cellular mechanisms. While implants can vary in design-including the original screw, press fit implants, and compressive osseointegration-they face common challenges to successful integration and maintenance of fixation within the host bone. Overcoming these challenges requires the understanding of the complex interactions between each element of OI. This review outlines (a) the basic components of OI, (b) the science behind both the bone-implant and the skin-implant interfaces, (c) the current challenges of OI, and (d) future opportunities within the field.

Mechanical Performance of Posterior Spinal Instrumentation and Growing Rod Implants: Experimental and Computational Study.

STUDY DESIGN: Experimental and computational study of posterior spinal instrumentation and growing rod constructs per ASTM F1717-15 vertebrectomy methodology for static compressive bending. OBJECTIVE: Assess mechanical performance of standard fusion instrumentation and growing rod constructs. SUMMARY OF BACKGROUND DATA: Growing rod instrumentation utilizes fewer anchors and spans longer distances, increasing shared implant loads relative to fusion. There is a need to evaluate growing rod's mechanical performance. ASTM F1717-15 standard assesses performance of spinal instrumentation; however, effects of growing rods with side-by-side connectors have not been evaluated. METHODS: Standard and growing rod constructs were tested per ASTM F1717-15 methodology; setup was modified for growing rod constructs to allow for connector offset. Three experimental groups (standard with active length 76 mm, and growing rods with active lengths 76 and 376 mm; n = 5/group) were tested; stiffness, yield load, and load at maximum displacement were calculated. Computational models were developed and used to locate stress concentrations. RESULTS: For both constructs at 76 mm active length, growing rod stiffness (49 ±â€Š0.8 N/mm) was significantly greater than standard (43 ±â€Š0.4 N/mm); both were greater than growing rods at 376 mm (10 ±â€Š0.3 N/mm). No significant difference in yield load was observed between growing rods (522 ±â€Š12 N) and standard (457 ±â€Š19 N) constructs of 76 mm. Growing rod constructs significantly decreased from 76 mm (522 ±â€Š12 N) to 376 mm active length (200 ±â€Š2 N). Maximum load of growing rods at 76 mm (1084 ±â€Š11 N) was significantly greater than standard at 76 mm (1007 ±â€Š7 N) and growing rods at 376 mm active length (392 ±â€Š5 N). Simulations with active length of 76 mm were within 10% of experimental mechanical characteristics; stress concentrations were at the apex and cranial to connector-rod interaction for standard and growing rod models, respectively. CONCLUSION: Growing rod constructs are stronger and stiffer than spinal instrumentation constructs; with an increased length accompanied a decrease in strength. Growing rod construct stress concentration locations observed during computational simulation are consistent with clinically observed failure locations. LEVEL OF EVIDENCE: 5.

Predicting the Effect of Bilateral Pelvic Osteotomy on Sagittal Alignment Correction and Surrounding Muscles: A Mathematical Model.

Study Design. Mathematical Model. Objectives. To investigate the relationship between pelvic osteotomy opening angle (OA) and its effect on spinopelvic sagittal parameters as well as the resting length of surrounding muscles. Methods. Predictive equations correlating OA with spinopelvic parameters were derived using geometric relationships. A geometric model calculated spinopelvic parameters (SVA, pelvic incidence [PI], PT, and T1 pelvic angle [TPA]) produced by progressively increasing the OA. These values were compared to optimal balance criteria in the literature. Four muscles crossing the osteotomy site were evaluated: Gluteus Medius (GMED), Gluteus Maximus (GMAX), Piriformis (P), and Tensor Fascia Lata (TFL). Insertion points were obtained from an OpenSim software model. GMAX and GMED were subdivided into 3 (anterior, middle, and posterior). Results. OA correlated negatively with PI, TPA, and SVA and positively with PT. From baseline SVA of 22 cm, OA 21° reduced SVA to 5cm. OA 23° reduced TPA to 14°. OA 30° increased PT to 20°. OA 26° decreased PI-LL to 10°. OA range of 26°-30° resulted in optimal sagittal deformity correction. OA correlated with SR positively for TFL and anterior GMED and negatively for the rest of muscles. For this OA, the SR approximately decreased 6%, 5%, 6%, 8%, and 5% for posterior GMED, anterior GMAX, middle GMAX, posterior GMAX, and P, respectively. It increased 8% and 4% for anterior GMED and TFL, respectively. Conclusion. Predictive relationships between osteotomy OA and spinopelvic parameters were shown, providing proof of concept that sagittal balance may be achieved via pelvic osteotomy.

A biomechanical study comparing minimally invasive anterior pelvic ring fixation techniques to external fixation.

INTRODUCTION: INFIX and Pelvic Bridge are two new minimally invasive surgical techniques for unstable pelvic ring injuries, and they have demonstrated early clinical success in small, single-center case-series. The primary objective of this study is to gather evidence speaking to the biomechanical stability of internal bridging methods relative to external fixation, with the expectation of biomechanical equivalence. METHODS: Ten human cadaveric pelvic specimens were dissected free of all skin, fat, organs, and musculature and were prepared with a partially unstable pelvic ring injury (OTA/AO 61-B). The specimens were randomized to two groups and were repaired and tested with anterior pelvic external fixation (APEF) and INFIX sequentially, or APEF and Pelvic Bridge sequentially. Testing was performed with each specimen mounted onto a servo-hydraulic testing frame with axial compression applied to the superior base of the sacrum under five axial loading/unloading sinusoidal cycles between 10 N and 1000 N at 0.1 Hz. Relative translational motion and rotation across the osteotomy site was reported as our primary outcome measures. Outcome measures were further analyzed using a Wilcoxon signed-rank test to determine differences between non-parametric data sets with significance defined as a p value < 0.05. RESULTS: We found no statistical difference in translation (p = 0.237, 0.228) or rotation (p = 0.278, 0.873) at the fracture site when comparing both new constructs to external fixation. Under the imposed loading protocol, no episodes of implant failure or failure at the bone-implant interface occurred. DISCUSSION: Our study provides the biomechanical foundation necessary to support future clinical trial implementation for pelvic fracture patients. While biomechanical stability of these newer, subcutaneous techniques is equivalent to APEF, the surgeon must take into account their technical abilities and knowledge of pelvic anatomy, patient-specific factors including body habitus, and the potential complications associated with each implant and the ability to avoid them.

Robust variational segmentation of 3D bone CT data with thin cartilage interfaces.

We present a two-stage variational approach for segmenting 3D bone CT data that performs robustly with respect to thin cartilage interfaces. In the first stage, we minimize a flux-augmented Chan-Vese model that accurately segments well-separated regions. In the second stage, we apply a new phase-field fracture inspired model that reliably eliminates spurious bridges across thin cartilage interfaces, resulting in an accurate segmentation topology, from which each bone object can be identified. Its mathematical formulation is based on the phase-field approach to variational fracture, which naturally blends with the variational approach to segmentation. We successfully test and validate our methodology for the segmentation of 3D femur and vertebra bones, which feature thin cartilage regions in the hip joint, the intervertebral disks, and synovial joints of the spinous processes. The major strength of the new methodology is its potential for full automation and seamless integration with downstream predictive bone simulation in a common finite element framework.

Examination of Skill Acquisition and Grader Bias in a Distal Radius Fracture Fixation Model.

OBJECTIVES: Primary: Assess the ability of faculty graders to predict the objectively measured strength of distal radius fracture fixation. Secondary: Compare resident skill variation and retention related to other knowable training data. DESIGN: Residents were allowed 60 minutes to stabilize a standardized distal radius fracture using an assigned fixed-angle volar plate. Faculty observed and subjectively graded the residents without providing real-time feedback. Objective biomechanical evaluation (construct strength and stiffness) was compared to subjective grades. Resident-specific characteristics (sex, PGY, and ACGME case log) were also used to compare the objective data. SETTING: A simulated operating room in our laboratory. PARTICIPANTS: Post-graduate year 2, 3, 4, and 5 orthopedic residents. RESULTS: Primary: Faculty were not successful at predicting objectively measured fixation, and their subjective scoring suggests confirmation bias as PGY increased. Secondary: Resident year-in-training alone did not predict objective measures (p = 0.53), but was predictive of subjective scores (p < 0.001). Skills learned were not always retained, as 29% of residents objectively failed subsequent to passing. Notably, resident-reported case-specific experience alone was inversely correlated with objective fixation strength. CONCLUSIONS: This testing model enabled the collection of objective and subjective resident skill scores. Faculty graders did not routinely predict objective measures, and their subjective assessment appears biased related to PGY. Also, in vivo case volume alone does not predict objective results. Familiar faculty teaching consistency, and resident grading by external faculty unfamiliar with tested residents, might alter these results.

Tobacco exposure and wound healing in head and neck surgical wounds.

OBJECTIVE: Smoking impairs wound healing, yet the underlying pathophysiological mechanisms are unclear. We evaluated tobacco-altered healing in head and neck surgery by studying the association between biomarkers and tobacco exposure, as well as cutaneous perfusion by smoking status. STUDY DESIGN: Prospective cohort study, tertiary/academic care center, 2011 to present. METHODS: Patients who required head and neck surgery were enrolled prospectively. Postsurgical drain fluid was collected 24 hours postoperatively. Biomarkers associated with postulated mechanisms of smoking-impaired healing were assayed. These included interleukin-1, -6, and -8; tumor necrosis factor- alpha; transforming growth factor-beta; epidermal growth factor (EGF); basic fibroblastic growth factor (bFGF); C-reactive protein; vascular endothelial growth factor; soluble FMS-like tyrosine kinase-1 (sFLT-1); and placental growth factor. Tobacco exposure and clinical outcomes were recorded. Two sample two-sided t tests evaluated the differences in cytokine levels by tobacco exposure. In a second cohort, cutaneous vascular assessment via indocyanine green angiography was compared by smoking status. RESULTS: Twenty-eight patients were enrolled with drain fluid collection. Twenty-one subjects were current/former smokers, whereas seven were never smokers. EGF was higher in never smokers than smokers in a statistically significant manner (P = 0.030). Likewise, sFLT-1 was significantly higher in never smokers (P = 0.011). Cutaneous angiography revealed nonsmokers to have significantly higher cutaneous perfusion than smokers. CONCLUSION: In this head and neck surgical cohort, significantly higher EGF and sFLT-1 levels in wound fluid were associated with never smoking, suggesting that smoking has adverse effects on the inflammatory phase of wound healing. Cutaneous angiography supports the detrimental effect of smoking on skin perfusion. These findings suggest the need for further study as well as therapeutic targets for smokers undergoing surgery. LEVEL OF EVIDENCE: 2b. Laryngoscope, 128:618-625, 2018.

Healing in peri-implant gap with BMP-2 and systemic bisphosphonate is dependent on BMP-2 dose-A canine study.

The bone-implant interface of cementless orthopedic implants can be described as a series of uneven sized gaps with discontinuous areas of direct bone-implant contact. Bridging these voids and crevices by addition of an anabolic stimulus to increase new bone formation can potentially improve osseointegration of implants. Bone morphogenetic protein 2 (BMP-2) stimulates osteoblast formation to increase new bone formation but also indirectly stimulates osteoclast activity. In this experiment, we investigate the hypothesis that osseointegration, defined as mechanical push-out and histomorphometry, depends on the dose of BMP-2 when delivered as an anabolic agent with systemic administration of the anti-resorptive agent zoledronate to curb an increase in osteoclast activity. Four porous coated titanium implants (one with each of three doses of surface-applied BMP-2 (15 µg; 60 µg; 240 µg) and untreated) surrounded by a 0.75 mm empty gap, were inserted into the distal femurs of each of twelve canines. Zoledronate IV (0.1 mg/kg) was administered 10 days into the observation period of 4 weeks. Bone-implant specimens were evaluated by mechanical push-out test and histomorphometry. The 15 µg implants had the best fixation on all mechanical parameters and largest surface area covered with new bone compared to the untreated, 60 and 240 µg implants, as well as the highest volume of new bone in the implant gap compared to 60 and 240 µg implants. The results in a canine implant model demonstrated that a narrow range of BMP-2 doses have opposite effects in bridging an empty peri-implant gap with bone, when combined with systemic zoledronate. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1406-1414, 2018.