Lateral interbody fusion for adjacent segment disease: a narrative review.

Background and Objective: Adjacent segment disease (ASD) is a late complication of lumbar fusion characterized by persistent symptoms correlating to radiographic changes in the levels immediately above or below the prior fusion. Lateral interbody fusion (LIF) through a direct lateral approach is a minimally invasive and effective surgical treatment for ASD. Biomechanically, LIF for ASD provides significantly decreased motion in multiple planes. While hardware failure and injury to the lumbar plexus are potential complications, these risks may be outweighed by decreased blood loss, shorter operating room (OR) times, and possibly superior patient reported visual analog scale (VAS) scores compared to traditional posterior spinal fusion (PSF) alone. The purpose of this review is to summarize the history, uses, outcomes, and future directions of LIF for ASD. Methods: A review of national databases (PubMed and SCOPUS) was performed using literature from 1900 to 2022. Keywords included terms "LATERAL" and "LUMBAR" and "INTERBODY" and "FUSION" and "ADJACENT" and "SEGMENT" and "DISEASE". Studies that aimed to describe the biomechanical, clinical course and complications, radiological outcomes, biomechanical aspects, need for revision surgery, and/or patient reported outcomes of the XLIF/LIF technique were included. Key Content and Findings: This review includes a brief overview of the natural history of ASD and current approaches to address it. It then summarizes the main indications and utilization of LIF to address ASD, summarizing reported outcomes in regard to biomechanical, clinical, and radiographic outcomes. Conclusions: LIF has emerged as a minimally invasive and effective surgical treatment for ASD. This mini-review suggests that LIF provides a solid foundational biomechanical construct that has been paired with good patient-reported, clinical, and radiographic outcomes. While further research is required, current literature suggests that LIF for ASD results in fewer complications, decreased morbidity, and decreased need for subsequent surgery compared to other commonly utilized techniques.

Influence of Anxiety and Depression on Opioid Use Following Lumbar Spine Fusion: A Large Database Study.

STUDY DESIGN: Retrospective database. OBJECTIVE: The purpose of this study was to understand how a mental health disorder, specifically anxiety and depression, influences a patient's postoperative opioid needs following single-level lumbar spine fusion. SUMMARY OF BACKGROUND DATA: Patients with spine pathology commonly demonstrate symptoms of an active psychiatric disorder. Mental health significantly influences how a patient perceives pain and a patient's opioid pain control needs after surgery. MATERIALS AND METHODS: The Pearldiver Patient Claims Database was used to identify patients undergoing single-level posterior spine fusion within the United States between 2010 and 2020. Patients were placed into 1 of 4 groups: those with a diagnosis of depression, those with a diagnosis of anxiety, those with a diagnosis of both anxiety and depression, and a control group. χ 2 tests were used to assess differences in the number of patients filling initial and additional opioid prescriptions for up to 90 days following their fusion. RESULTS: The control group filled significantly more initial opioid prescriptions within the first 90 days following their spine fusion ( P <0.001). However, there was no difference among the study groups in regard to the additional need for prescriptions. CONCLUSION: Patients with mental health diagnoses may present as complex patients to spine surgeons; however, this study suggests they do not require additional opioid pain control following a single-level lumbar fusion.

Influence of Anxiety and Depression on Opioid Use After Cervical Spine Fusion: An Analysis of a National Claims Database.

Patients with spine pathology demonstrate an above average rate of active psychiatric disorders, which can influence their recovery. This study was designed to understand how mental health diagnoses (ie, anxiety and depression) influence a patient's postoperative need for opioids after a single level cervical spine fusion. The PearlDiver database was used to identify patients. Patients were placed into one of four groups: those with a diagnosis of depression, those with a diagnosis of anxiety, those with a diagnosis of both anxiety and depression, and a control group. Chi-square tests were used to assess differences in the number of patients filling initial and additional opioid prescriptions for up to 90 days after their fusion. A total of 168,967 patients who underwent an elective cervical spine fusion in the United States between 2010 and 2021 were included in this study. The control group filled significantly more opioid prescriptions within the first 90 days after their cervical fusion (P<.001). There was no difference among the study groups regarding the need to fill additional opioid prescriptions. Patients with a diagnosis of depression and/or anxiety may present as complex patients; however, results suggest they do not need additional opioids for pain control after a single level cervical spine fusion. [Orthopedics. 2024;47(2):89-94.].

Low Body Mass Index Patients Undergoing an Anterior Lumbar Fusion May Have an Increased Risk of Perioperative Complications.

BACKGROUND: Previous research has shown that underweight patients may be at a greater risk of experiencing postsurgical complications. The purpose of this study was to investigate the association between body mass index (BMI) and postoperative complications following single-level anterior lumbar fusion (ALF). METHODS: All single-level elective ALF procedures performed between 2010 and 2020 were identified in the PearlDiver Mariner Database. Patients were separated into 6 groups based on the World Health Organization BMI classifications. Differences in postsurgical complications (ie, deep vein thrombosis, pulmonary embolism, surgical site infection, hardware malfunction, wound dehiscence, and blood transfusion) among BMI categories were assessed using a χ2 contingency test. RESULTS: Results indicated that underweight patients (BMI <20) were at a significantly greater risk of developing deep vein thromboses, experiencing hardware malfunction, and requiring blood transfusion compared with any other BMI classification (P < 0.001). Results also demonstrated that underweight individuals had similar risks of developing surgical site infection and wound dehiscence compared with patients classified as having obesity class III. CONCLUSION: Underweight patients may be at a greater risk than currently believed of experiencing postoperative complications following single-level ALF procedures. CLINICAL RELEVANCE: Patients with a BMI of 20 or less should be carefully evaluated prior to surgical intervention to ensure they are optimized for surgery.

The effect of cannabis use on postoperative complications in patients undergoing spine surgery: A national database study.

Background: With the increased use of cannabis in the US, there is a significant need to understand the medical complications associated with its use in relationship to a surgical population. Cannabis has mainly been studied with respect to its qualities of pain treatment, yet few studies have investigated post-surgical complications associated with its use. Therefore, the purpose of this study was to explore the effect of cannabis use on complications in spine surgery, and compare these complications rates to opioid-related complications. Methods: This was a retrospective study conducted using the PearlDiver Database. Using ICD codes 40,989 patients that underwent lumbar spine fusion between January 2010 and October 2020 were identified and divided into 3 study groups (i.e., control, patients with known opioid use disorder, and patients identified as cannabis users). Differences in the incidence of complications within 30 days of the index procedure and pseudarthrosis rates at 18 months postindex procedure were assessed among study groups using a multivariate logistic regression. Results: Of 12.4% study population used cannabis and 38.8% had a known opioid use disorder. Results indicated increased odds of experiencing a VTE, hypoxia, myocardial infarction, and arrhythmia for both opioid and cannabis users compared to controls; however, when controlling for tobacco use there were no increased odds of complications within the cannabis group. The pseudarthrosis rate was greater in cannabis users (2.4%) than in controls (1.1%). Conclusions: The pseudarthrosis rate was significantly greater in patients using cannabis and opioids compared to the control group. However, when controlling for tobacco use, results suggested a possible negative synergistic between cannabis use and concomitant tobacco use that may influence bone fusion.

Cannabis use is associated with decreased opioid prescription fulfillment following single level anterior cervical discectomy and fusion (ACDF).

Background: Recently, there has been increasing legalization of marijuana within the United States, however data are mixed with respect to its efficacy in treating acute pain. Our goal was to identify a difference in opioid utilization in patients with known cannabis use before anterior cervical discectomy and fusion (ACDF) compared with those that report no cannabis use. Methods: This study was a retrospective case-control design using PearlDiver. Patients who underwent a single level ACDF between January 2010 and October 2020, were included. Patients were placed in the study group if they had a previous diagnosis of cannabis use, dependence, or abuse. Patients were excluded if they were under the age of 18 or if they had filled an opioid prescription within 3 months of their procedure. A control group was then created using a propensity score match on age, gender, and Charleston comorbidity index (CCI), and had no diagnosis of cannabis use. The primary outcome was the number of morphine milliequivalents (MME) dispensed per prescription following surgery. Results: A total of 1,339 patients were included in each group. The number of patients filling prescriptions was lower in the cannabis group than in the control group at 3 days postoperatively (p<.001). The average total MME per day as prescribed was lower in the cannabis group than the control group at 60 days post-op (48.5 vs. 59.4, respectively; p=.018). Conclusions: Patients who had a previous diagnosis of cannabis use, dependence or abuse filled fewer opioid prescriptions postoperatively (at 3 days postoperatively) and required lower doses (reduced average daily MME, at 60 days postoperatively) when compared with the control group.

Utility of Erector Spinae Plane Blocks for Postoperative Pain Management and Opioid Reduction Following Lumbar Fusions.

STUDY DESIGN: Retrospective. OBJECTIVE: The purpose of this study was to determine the utility of the erector spinae plane regional anesthesia (ESP) block in reducing opioid medication usage and postanesthesia care unit length of stay (PACU-LOS) for patients undergoing either a posterior or transforaminal lumbar interbody fusions (PLIF/TLIF). SUMMARY OF BACKGROUND DATA: Posterior lumbar spine fusion is a common surgical procedure typically associated with significant postoperative pain. Poorly controlled postoperative pain can lead to a number of poor outcomes. Although opioids are a mainstay for pain control, they are associated with adverse effects and a risk of dependence. Therefore, multimodal pain control has become more prevalent in orthopedics and combines traditional opioid and nonopioid pain mediation with general anesthesia protocols and regional nerve blocks. MATERIALS AND METHODS: A retrospective chart review was conducted for patients undergoing PLIFs or TLIFs between 2019 and 2021. Patients were placed into 2 groups, those receiving an ESP block and those that did not. T tests assuming unequal variances were used to assess differences in pain scores, opioid consumption, and PACU-LOS between groups. RESULTS: The study group demonstrated a 35% reduction in opioid use ( P =0.016), a 16% reduction in pain with activity ( P =0.042), and a 9.7% reduction in pain at rest ( P =0.219) compared with the control group. There were no significant differences in PACU-LOS between groups ( P =0.314). CONCLUSION: The use of an ESP block for patients undergoing PLIFs and TLIFs appears to be a safe and effective means to manage postoperative pain and reduce opioid consumption.

Utility of the transversus abdominis plane and rectus sheath blocks in patients undergoing anterior lumbar interbody fusions.

BACKGROUND CONTEXT: Anterior lumbar interbody fusion (ALIF) is a well-established technique to address numerous pathological conditions of the spine and to restore sagittal spine balance. Improving patient comfort and reducing opioid consumption following lumbar fusions is a significant goal for spine surgeons. Therefore, there is a growing need to explore multimodal options for pain management post-surgery. PURPOSE: Determine the effectiveness of combined transversus abdominis plane (TAP) and rectus sheath (RS) blocks in those undergoing (ALIF) as compared to a historical control. STUDY DESIGN/SETTING: Retrospective comparative cohort performed at a tertiary referral orthopedic specialty hospital. PATIENT SAMPLE: Of the 175 patients (88 patients received a combined regional block) who underwent an ALIF between January 1, 2018 and August 1, 2021. OUTCOME MEASURES: Pain scores both during activity and at rest, opioid consumption during the first 72 hours postoperatively, total postoperative anesthesia care unit length of stay (PACU LOS), 30-day emergency department visits, 30-day readmissions, and unplanned returns to the operating room. METHODS: Charts of patients undergoing an ALIF during the open period for this study were placed into two groups: those that received combined regional anesthesia and those that did not. A t test assuming unequal variances was used to determine if there were differences in outcome variables between the two groups. RESULTS: The study group, those receiving the combine block, demonstrated a statistically significant reduction in opioid pain medicine (24.8%), reported pain (10-13%), and PACU LOS (18.7%). There were no differences in complication rates between the two groups. CONCLUSIONS: The combined use of TAP and RS blocks appears to be a well-tolerated and effective means of pain management in this patient cohort.

Cervical and Lumbar Disc Arthroplasty: A Review of Current Implant Design and Outcomes.

While spinal disc pathology has traditionally been treated using fusion-based procedures, recent interest in motion-preserving disc arthroplasties has grown. Traditional spinal fusion is associated with loss of motion, alteration of native spine kinematics, and increased risks of adjacent segment disease. The motion conferred by disc arthroplasty is believed to combat these complications. While the first implant designs resulted in poor patient outcomes, recent advances in implant design and technology have shown promising radiographic and clinical outcomes when compared with traditional fusion. These results have led to a rapid increase in the utilization of disc arthroplasty, with rates of cervical arthroplasty nearly tripling over the course of 7 years. The purpose of this review was to discuss the evolution of implant design, the current implant designs utilized, and their associated outcomes. Although disc arthroplasty shows significant promise in addressing some of the drawbacks associated with fusion, it is not without its own risks. Osteolysis, implant migration, and the development of heterotopic ossification have all been associated with disc arthroplasty. As interest in these procedures grows, so does the interest in developing improved implant designs aimed at decreasing these adverse outcomes. Though they are still relatively new, cervical and lumbar disc arthroplasty are likely to become foundational methodologies for the treatment of disc pathology.

Spinal Implant Osseointegration and the Role of 3D Printing: An Analysis and Review of the Literature.

The use of interbody implants for spinal fusion has been steadily increasing to avoid the risks of complications and donor site morbidity when using autologous bone. Understanding the pros and cons of various implant designs can assist the surgeon in choosing the ideal interbody for each individual patient. The goal of these interbody cages is to promote a surface area for bony ingrowth while having the biomechanical properties to support the axial skeleton. Currently, the majority of interbody implants consists of metal or polyether ether ketone (PEEK) cages with bone graft incorporated inside. Titanium alloy implants have been commonly used, however, the large difference in modulus of elasticity from bone has inherent issues. PEEK implants have a desirable surface area with the benefit of a modulus of elasticity closer to that of bone. Unfortunately, clinically, these devices have had increased risk of subsidence. More recently, 3D printed implants have come into the market, providing mechanical stability with increased surface design for bony ingrowth. While clinical outcomes studies are limited, early results have demonstrated more reliable and quicker fusion rates using 3D custom interbody devices. In this review, we discuss the biology of osseointegration, the use of surface coated implants, as well as the potential benefits of using 3D printed interbodies.

Spinopelvic Fixation.

Fixation at the lumbosacral junction continues to be a challenge for spine surgeons despite advances in spinal instrumentation techniques. The poor bone quality of the sacrum, the complex regional anatomy, and the tremendous biomechanical forces at the lumbosacral junction contribute to the high rates of instrumentation-related complications. Although many spinopelvic fixation techniques have been reported, only a few are still widely used because of the high complication rates associated with previous techniques. Spinopelvic fixation has numerous indications. Long-segment lumbar and thoracolumbar fusions to the sacrum are the most common scenarios in which instrumentation is extended to the pelvis. Surgeons performing complex spinal reconstruction should be familiar with the available techniques, including their potential risks and complications.

Surgical Management of Cervical Spondylotic Myelopathy.

Cervical spondylotic myelopathy (CSM) is a common cause of neurologic impairment in adults worldwide. Numerous studies have investigated the pathophysiology of CSM, which has provided surgeons with insight on the important factors that lead to the symptoms and deficits observed in patients who have CSM. However, further analysis of many unknown aspects of CSM is required to fully understand the disease and potential alternative treatment modalities. The diagnosis of CSM is based on a patient's history and physical examination and then confirmed with imaging studies. Progression, symptomatology, and imaging findings may vary by patient. Because of the variability of CSM, the disease course and a patient's response to treatment are difficult to predict. CSM can be managed either nonsurgically or it can be managed surgically via posterior or anterior cervical approaches, each of which has its own indications and possible complications.

Knee Disarticulation for a Total Knee Arthroplasty Periprosthetic Fracture.

Total knee arthroplasty, although a very successful surgery, can present the patient with several potential complications, including the risk for periprosthetic fractures. Complications involving periprosthetic fractures after total knee arthroplasty can present a complex clinical scenario for orthopedic surgeons. To date, adequate literature exists to guide surgeons in approaching most periprosthetic fractures; however, standard operating procedure can fall short when confronted with more complex clinical scenarios. The authors present an alternative approach, falling outside the traditional paradigm, to addressing a periprosthetic tibial fracture in the setting of a previous total knee arthroplasty. Given both the patient's physiological factors and the inherent factors of the fracture, the authors found that the first-line treatments for periprosthetic fracture, including open reduction and internal fixation and joint revision, were inadequate and posed more potential risks than benefits for the patient. In light of this situation, the authors elected to treat this patient's periprosthetic fracture with a through knee amputation, as this provided the patient with the lowest cost in morbidity while still addressing the fracture. [Orthopedics. 2016; 39(4):e775-e778.].

Cervical total disc replacement exhibits similar stiffness to intact cervical functional spinal units tested on a dynamic pendulum testing system.

BACKGROUND CONTEXT: The pendulum testing system is capable of applying physiologic compressive loads without constraining the motion of functional spinal units (FSUs). The number of cycles to equilibrium observed under pendulum testing is a measure of the energy absorbed by the FSU. OBJECTIVE: To examine the dynamic bending stiffness and energy absorption of the cervical spine, with and without implanted cervical total disc replacement (TDR) under simulated physiologic motion. STUDY DESIGN: A biomechanical cadaver investigation. METHODS: Nine unembalmed, frozen human cervical FSUs from levels C3-C4 and C5-C6 were tested on the pendulum system with axial compressive loads of 25, 50, and 100 N before and after TDR implantation. Testing in flexion, extension, and lateral bending began by rotating the pendulum to 5°, resulting in unconstrained oscillatory motion. The number of rotations to equilibrium was recorded and the bending stiffness (Newton-meter/°) was calculated and compared for each testing mode. RESULTS: In flexion/extension, with increasing compressive loading from 25 to 100 N, the average number of cycles to equilibrium for the intact FSUs increased from 6.6 to 19.1, compared with 4.1 to 12.7 after TDR implantation (p<.05 for loads of 50 and 100 N). In flexion, with increasing compressive loading from 25 to 100 N, the bending stiffness of the intact FSUs increased from 0.27 to 0.59 Nm/°, compared with 0.21 to 0.57 Nm/° after TDR implantation. No significant differences were found in stiffness between the intact FSU and the TDR in flexion/extension and lateral bending at any load (p<.05). CONCLUSIONS: Cervical FSUs with implanted TDR were found to have similar stiffness, but had greater energy absorption than intact FSUs during cyclic loading with an unconstrained pendulum system. These results provide further insight into the biomechanical behavior of cervical TDR under approximated physiologic loading conditions.

Incidence and cost of treating axis fractures in the United States from 2000 to 2010.

STUDY DESIGN: Retrospective database analysis. OBJECTIVE: To examine the incidence of hospitalization, treatment, and cost of caring for patients with axis (C2) fractures. SUMMARY OF BACKGROUND DATA: The incidence of C2 fractures in the elderly seems to be increasing, however, a comprehensive analysis of the incidence, treatment, and cost of treating C2 fractures has not been previously reported. METHODS: The Nationwide Inpatient Sample from 2000 to 2010 was used to identify patients with C2 fracture without neurological injury (International Classification of Disease, Ninth Revision, Clinical Modification code 805.02). Examined variables included age, International Classification of Disease, Ninth Revision, Clinical Modification injury severity score, comorbidities, mortality, hospital length of stay, treatments, and total inpatient hospitalization charge. Charges were adjusted for inflation to 2010 US dollars as well as for cost-to-charge ratios. RESULTS: In total, 31,129 patients with C2 fracture were identified. From 2000 to 2010 the incidence of C2 fracture hospitalization increased in all age groups (P < 0.0001). The most rapid increase was in patients older than 84 years, who experienced a 3-fold increase from 3.18 to 9.77 hospitalizations per 10,000 individuals per year (P < 0.0001). From 2000 to 2010, the rate of halo vest placement decreased from 25.2% to 10.4% (P < 0.0001), whereas the rate of surgical intervention increased from 13.1% to 16.5% (P = 0.029). For nonoperatively treated patients, the mean hospitalization charge per patient increased from $39,346 in 2000 to $63,222 in 2010, and for surgically treated patients, it increased from $70,784 in 2000 to $133,064 in 2010 (P < 0.0001). During the decade, the estimated charges for annual inpatient care for patients with C2 fracture in the United States increased 4.7-fold from $334,138,919 to $1,577,254,958 (P < 0.0001). CONCLUSION: The incidence of C2 fracture hospitalizations increased dramatically from 2000 to 2010, with the most rapid increase in the elderly represented by a greater than 3-fold increase for patients older than 84 years. The inpatient charges for treating C2 fractures have risen faster than the increased incidence, with a 4.7-fold increase in hospital charges resulting in estimated annual charges of more than $1.5 billion in 2010. LEVEL OF EVIDENCE: 3.

Wrong-site Spine Surgery.

Wrong-site spine surgery is an adverse event that has potentially devastating consequences for the patient as well as the surgeon. Despite substantial efforts to prevent wrong-site spine surgery, this complication continues to occur and has the potential for serious medical, personal, and legal repercussions. Although systems-based prevention methods are effective in identifying the proper patient, procedure, and region of the spinal column, they cannot be relied on to establish the correct vertebral level during the operation. The surgeon must design and implement a patient-specific protocol to ensure that the appropriate operation is performed on the correct side and level or levels of the spinal column.

Benign tumors of the spine.

Benign tumors in the spine include osteoid osteoma, osteoblastoma, aneurysmal bone cyst, osteochondroma, neurofibroma, giant cell tumor of bone, eosinophilic granuloma, and hemangioma. Although some are incidental findings, some cause local pain, radicular symptoms, neurologic compromise, spinal instability, and deformity. The evaluation of spinal tumors includes a thorough history and physical examination, imaging, sometimes laboratory evaluation, and biopsy when indicated. Appropriate treatment may be observational (eg, eosinophilic granuloma) or ablative (eg, osteoid osteoma, neurofibroma, hemangioma), but generally is surgical, depending on the level of pain, instability, neurologic compromise, and natural history of the lesion. Knowledge of the epidemiology, common presentation, imaging, and treatment of benign bone tumors is essential for successful management of these lesions.

The effects of GDF-5 and uniaxial strain on mesenchymal stem cells in 3-D culture.

Recent endeavors in tissue engineering have attempted to identify the optimal parameters to create an artificial ligament. Both mechanical and biochemical stimulation have been used by others to independently modulate growth and differentiation, although few studies have explored their interactions. We applied previously described fabrication techniques to create a highly porous (90%-95% porosity, 212-300 microm), 3-D, bioabsorbable polymer scaffold (polycaprolactone). Scaffolds were coated with bovine collagen, and growth and differentiation factor 5 (GDF-5) was added to half of the scaffolds. Scaffolds were seeded with mesenchymal stem cells and cultured in a custom bioreactor under static or cyclic strain (10% strain, 0.33 Hz) conditions. After 48 hours, both mechanical stimulation and GDF-5 increased mRNA production of collagen I, II, and scleraxis compared to control; tenascin C production was not increased. Combining stimuli did not change gene expression; however, cellular metabolism was 1.7 times higher in scaffolds treated with both stimuli. We successfully grew a line of mesenchymal stem cells in 3-D culture, and our initial data indicate mechanical stimulation and GDF-5 influenced cellular activity and mRNA production; we did not, however, observe additive synergism with the mechanical and biological stimuli.

The effects of local bFGF release and uniaxial strain on cellular adaptation and gene expression in a 3D environment: implications for ligament tissue engineering.

The objectives of this investigation were (1) to characterize the growth factor release profile of a basic fibroblast growth factor (bFGF)-coated three-dimensional (3D) polymer scaffold under static and cyclically strained conditions, and (2) to delineate the individual and collective contributions of locally released bFGF and mechanical strain on cellular morphology and gene expression in this 3D system. Scaffolds were treated with I(125)-bFGF and subjected to mechanical strain or maintained in a static environment and the media sampled for factor release over a period of 6 days. Over the first 10 hours, a burst release of 25% of the incorporated growth factor into the surrounding media was noted. At 24 hours, approximately 40% of the bFGF was released into the media, after which steady state was achieved and minimal subsequent release was noted. Mechanical stimulation had no effect on growth factor release from the scaffold in this system. To test the concerted effects of bFGF and mechanical stimulation on bone marrow stromal cells (BMSCs), scaffolds were loaded with 0, 100, or 500 ng of bFGF, seeded with cells, and subjected to mechanical strain or maintained in a static environment. Scaffolds were harvested at 1, 7, and 21 days for RT-PCR and histomorphometry. All scaffolds subjected to growth factor and/or mechanical stimulation demonstrated cellular adherence and spreading at 21 days. Conversely, in the absence of both bFGF and mechanical stimulation, cells demonstrated minimal cytoplasmic spread. Moreover, at 21 days, cells subjected to both mechanical stimulation and bFGF (500 ng) demonstrated the highest upregulation of stress-resistive (collagen I, III) and stress-responsive proteins (tenascin-C). The effect of growth factor may be dose sensitive, however, as unstrained scaffolds treated with 100 ng of bFGF demonstrated upregulation of gene expression comparable to strained scaffolds treated with lower doses of bFGF (0 or 100 ng). In conclusion, results from this study suggest that the stimulatory effects of bFGF are dose sensitive and appear to be influenced by the addition of mechanical strain. The concurrent application of biochemical and mechanical stimuli may be important in promoting the adaptation of BMSCs and driving the transcription of genes essential for synthesis of a functional ligament replacement tissue.