Developing an Inclusive Training Environment: Accommodations in Physical Medicine and Rehabilitation Residency Training for Residents With a Disability.

ABSTRACT: This study examines the challenges and accommodations for medical residents with disabilities within physical medicine and rehabilitation training programs. Medical residency presents unique stressors and responsibilities, with the potential for added complexities for residents with disabilities. Few data exist regarding the prevalence and experiences of people with disabilities as medical trainees and the limited studies available highlight an underrepresentation of individuals with disability in medical training and practice. Through cross-sectional surveys administered to physical medicine and rehabilitation residents, this research assesses disability prevalence, characterizations, barriers to training, and accommodations provided. Of 140 respondents, 9.3% identified as having disabilities, with varying prevalence among genders and disability types. Results revealed distinct challenges for residents with mobility and nonmobility disabilities, spanning learning environments, standardized testing, procedural skills, and accessibility. Self-provided accommodations exceeded program-provided ones, indicating room for improvement in program support. These findings underscore the need for proactive dialog between residents and leadership to address barriers, enhance accommodations, and create an inclusive training environment. The study's insights emphasize the importance of advocating for equal opportunities and cultivating supportive conditions to enable individuals with disabilities to thrive in medical residency programs, ultimately contributing to more diverse and inclusive medical communities.

Knee Extensor Mechanism Tendinopathy: Evaluation, Treatment, and Prevention.

ABSTRACT: Knee extensor mechanism tendinopathy, including patellar and quadriceps tendinopathy, is common among athletes and those involved in jumping sports. It is largely a clinical diagnosis that presents as anterior knee pain and stiffness with associated tenderness over the affected tendon. Imaging modalities, including ultrasound and/or magnetic resonance imaging, may be helpful with the diagnosis of difficult cases or in the planning of interventional procedures. Focused and structured rehabilitation using eccentric or heavy slow resistance exercise in conjunction with load management is important for recovery. Adjuvant therapies (e.g., injections or surgery) may be necessary in recalcitrant cases or those with insufficient response to rehabilitation efforts. Prevention strategies focus on improving biomechanics, landing mechanism and lower-extremity balance, flexibility, and strength.

Sports Medicine Physician Decision-Making, Practice Changes, and Mental Health During the Early Phase of the SARS-CoV-2 Global Pandemic.

OBJECTIVE: The SARS-CoV-2 pandemic has had a profound effect on the healthcare system. This study aimed to identify its effects on sports medicine physicians during the early phase of this pandemic. DESIGN: Survey study. SETTING: Sports medicine providers. PARTICIPANTS: Physician members of the American Medical Society for Sports Medicine were surveyed between March 25 and April 4, 2020. A total of 810 responses were obtained from 2437 physicians who viewed the survey. INTERVENTIONS: The survey consisted of questions examining demographics, prepandemic practice patterns, anxiety and depression screening, and new beliefs and behaviors following government-based medical policy changes resulting from the pandemic. MAIN OUTCOME MEASURES: Changes in clinical volume and treatment practices, Patient Health Questionnaire (PHQ-4). RESULTS: The mean in-person clinic visits reduced to 17.9%, telephone visits to 24.4%, telemedicine (video) visits to 21.8%, and procedural visits to 13.8% of prepandemic practice volume. The mean PHQ-4 scores for physicians were 2.38 ± 2.40. Clinic and procedural volumes were reduced less by male physicians, as well as more experienced physicians, nonphysical medicine and rehabilitation training background, in government or private practice, and in the Southern region of the United States (P < 0.05). Physicians were more likely to reduce their anti-inflammatory (37.8% decreasing vs 6.8% increasing, P < 0.001) and opioid (10.5% vs 6.8%, P = 0.003) prescriptions rather than increase. CONCLUSIONS: During the early phase of the SARS-COV-2 pandemic sports medicine physicians reported reducing in-person evaluation, management, and procedure volume by over 80%. Multiple demographic and geographic factors were associated with practice volume changes.

Ultrasound-guided glenohumeral joint injections for shoulder pain in ALS: A case series.

Introduction: Shoulder pain is a common secondary impairment for people living with ALS (PALS). Decreased range of motion (ROM) from weakness can lead to shoulder pathology, which can result in debilitating pain. Shoulder pain may limit PALS from participating in activities of daily living and may have a negative impact on their quality of life. This case series explores the efficacy of glenohumeral joint injections for the management of shoulder pain due to adhesive capsulitis in PALS. Methods: People living with ALS and shoulder pain were referred to sports medicine-certified physiatrists for diagnostic evaluation and management. They completed the Revised ALS Functional Rating Scale and a questionnaire asking about their pain levels and how it impacts sleep, function, and quality of life at baseline pre-injection, 1-week post-injection, 1 month post-injection, and 3 months post-injection. Results: We present five cases of PALS who were diagnosed with adhesive capsulitis and underwent glenohumeral joint injections. Though only one PALS reported complete symptom resolution, all had at least partial symptomatic improvement during the observation period. No complications were observed. Conclusions: People living with ALS require a comprehensive plan to manage shoulder pain. Glenohumeral joint injections are safe and effective for adhesive capsulitis in PALS, but alone may not completely resolve shoulder pain. Additional therapies to improve ROM and reduce pain should be considered.

Telemedicine During COVID-19 for Outpatient Sports and Musculoskeletal Medicine Physicians.

INTRODUCTION: The global pandemic due to SARS-CoV-2 has resulted in an expansion of telemedicine. Measures of quality and barriers for rapid use by patients and physicians are not well described. OBJECTIVE: To describe results from a quality improvement initiative during a rapid adoptive phase of telemedicine during the pandemic. DESIGN: Patient and physician satisfaction with synchronous audiovisual telemedicine visits was measured during the early adoptive phase (6 April 2020-17 April 2020) within the division of sports medicine in an academic Physical Medicine and Rehabilitation (PM&R) department. Patients were invited to participate in a quality improvement initiative by completing an online survey at the end of a telemedicine visit. Physicians completed a separate survey. PRIMARY OUTCOME MEASURES: Patient measures included visit type, duration of encounter, quality, and satisfaction. Physicians reported on experiences performed telemedicine. RESULTS: Surveys were completed by 119 patients (293 telemedicine encounters, response rate 40.6%) and 14 physiatrists. Telemedicine was utilized primarily for follow-up visits (n = 74, 70.6%), and the most common duration was 15 to 29 minutes. Patients rated their telemedicine visit as "excellent" or "very good" across measures (91.6%-95.0%) including addressing concerns, communication, developing a treatment plan, convenience, and satisfaction. Value of completing a future telemedicine visit was measured at 84.9%. Most reported estimated travel time saved was in excess of 30 minutes. Rate of no-show was 2.7%. Most physicians (57.1%) had no prior experience with telemedicine visits, and most were comfortable performing these visits after completing 1 to 4 sessions (71%). Nearly all physicians (92.9%) rated their telemedicine experience as very good or excellent. The key barrier identified for telemedicine was technical issues. All physicians reported plans to perform telemedicine visits if reimbursement continues. CONCLUSIONS: In summary, rapid expansion of telemedicine during the COVID-19 pandemic was well-received by a majority of patients and physicians. This suggests feasibility in rapid expansion of telemedicine for other outpatient sports medicine practices.

Patient-reported auditory handicap measures following mild traumatic brain injury.

OBJECTIVES/HYPOTHESIS: Few studies have specifically addressed auditory complaints in patients with nonblast mild traumatic brain injury (mTBI). Herein, we aimed to investigate auditory symptoms in patients following mTBI using patient-reported outcome measures. STUDY DESIGN: Retrospective analysis of prospectively collected data in a tertiary-care hospital. METHODS: The patients included those with mTBI (cases) and those without mTBI (controls). Individuals (≥18 years old) with and without mTBI were screened. Exclusion criteria included history of otologic disorders, blast injury, or occupational noise exposure. Primary outcomes included the Hearing Handicap Inventory for Adults (HHIA), Tinnitus Handicap Inventory (THI), and Hyperacusis Questionnaire (HQ). Secondary outcomes included subjective auditory complaints. RESULTS: From September 2017 to September 2018, 52 patients with mTBI and 55 controls met inclusion and exclusion criteria. The mean time between mTBI and survey intake was 70.6 months. The mean age and gender were 51.5 years old and 73% female in the mTBI group, and 46.1 years old and 56.3% female in the control group (P = .112 and P = .105, respectively). Patients with mTBI reported hyperacusis (67.3% of all mTBI patients), hearing loss (61.5%), and tinnitus (61.5%), compared to 8.3%, 12.7%, and 16.4%, respectively, for control subjects (P < .0001). The mean HHIA score in the mTBI group was 38.3 versus 8.5 in controls (P = .002). The mean THI score was 27.4 in the mTBI group and 3.1 in controls (P < .0001). The mean HQ score was 26.5 in mTBI group and 7.3 in controls (P = .001). CONCLUSIONS: Auditory symptoms and associated handicap were common in patients with nonblast mTBI compared to age-matched controls. Findings have implications for the pathophysiology and management of symptoms in this patient population. LEVEL OF EVIDENCE: 3 Laryngoscope, 130:761-767, 2020.

Using a Workshop Format for Physiatry Trainees in the Management of Acute Sports-Related Concussion.

Select residency and medical student training programs have developed and researched skill-based workshops, focusing on mastering a surgical or communication skill; however, they are less frequently studied in physiatry residency programs. Given the importance of concussion care in physiatric practice, this study sought to measure the effectiveness of a novel sports-related concussion workshop. Based on the 5th International Consensus Statement on Concussion in Sport, a 6-hr concussion workshop was developed. Participants were administered a preworkshop and postworkshop questionnaire to gauge level of comfort managing various aspects of concussion, case-based questions to assess participant knowledge, and questions regarding satisfaction with workshop-based training sessions. Sixteen participants, ranging from PGY-2 to PGY-5, were included in the analyses, with significant gains (P < 0.0001 to P = 0.0045) made in all measures of comfort managing sports-related concussion; the study was unable to detect a statistically significant improvement in knowledge as assessed by the patient vignettes (P = 0.17), but participants did report high levels of satisfaction with workshop-based training sessions. Thus, workshop-based physiatry trainee education sessions can be used to teach trainees certain skills or provide comprehensive training in the management of a specific condition. Participants demonstrated improved comfort managing concussion, a trend toward improved knowledge, and a high degree of satisfaction with the content's method delivery.

The Relationship Between Body Mass Index and Fluoroscopy Time During Intraarticular Hip Injection: A Multicenter Cohort Study.

BACKGROUND: Higher body mass index (BMI) is associated with difficulty in obtaining imaging studies. While there is a small body of literature regarding the relationship between fluoroscopy time and BMI during injections for pain management, this has not been studied for intraarticular (IA) hip injections. Further, in academic training centers, trainee involvement may affect this relationship. OBJECTIVE: To determine the relationship between BMI and fluoroscopy time during IA hip injections, both with and without involvement of a trainee. STUDY DESIGN: Multicenter retrospective cohort study. SETTING: Three academic, outpatient musculoskeletal and pain medicine centers. METHODS: Patients who underwent fluoroscopically guided IA hip injections with encounter data regarding fluoroscopy time during the procedure and BMI were included. Mean and standard deviation fluoroscopy time were recorded. Comparisons were made between BMI categories of normal (18.5 - 24.9 kg/m2), overweight (25.0 - 29.9 kg/m2), and obese (greater than or equal to30.0 kg/m2). Statistical significance was set at P = 0.01 due to multiple comparisons. RESULTS: A total of 559 IA hip injections are represented in this cohort. Patients had a mean age of 58 (standard deviation [SD] 14) years and 63% were women. There was no significant difference in fluoroscopy time when comparing BMI categories (P = 0.02). However, when trainees were not involved in the injection, fluoroscopy times were significantly shorter with decreasing BMI category, with normal weight patients requiring the shortest fluoroscopy times (P = 0.01). LIMITATIONS: This study evaluated total fluoroscopy time, not radiation dose exposure per injection, which provides more direct and precise information with regard to provider and patient radiation exposure and overall safety. Future study of the impact of BMI on radiation dose during fluoroscopically guided IA hip injections is needed. CONCLUSIONS: Fluoroscopy times during IA hip injections increase with higher BMI categories in a statistically significant manner when performed by experienced clinicians but this relationship is not observed when injections are performed with a trainee in a teaching institution. This finding appears to be related to longer fluoroscopy time required to complete an IA hip injection in patients with lower BMI when a trainee is involved. KEY WORDS: Hip, injections, obesity, overweight, body mass index, fluoroscopy, radiation, pain.

Prevention, Evaluation, and Rehabilitation of Cycling-Related Injury.

The unique quality of the bicycle is its ability to accommodate a wide variety of injuries and disabilities. Cycling for recreation, transportation, and competition is growing nationwide, and has proven health and societal benefits. The demands of each type of cycling dictate the necessary equipment, as well as potential for injury. Prevention of cycling-related injury in both the athlete and the recreational cyclist involves understanding the common mechanisms for both traumatic and overuse injury, and early correction of strength and flexibility imbalances, technique errors, and bicycle fit.

Pain Reduction and Repeat Injections After Transforaminal Epidural Injection With Particulate Versus Nonparticulate Steroid for the Treatment of Chronic Painful Lumbosacral Radiculopathy.

BACKGROUND: The corticosteroid choice for a lumbar transforaminal epidural steroid injection (TFESI) remains controversial. Whether to utilize particulate or nonparticulate steroid preparations for these injections remains an unanswered question in the literature. OBJECTIVE: To determine if a particulate or nonparticulate steroid is more effective in the treatment of electromyography (EMG)-confirmed lumbosacral radiculopathy. DESIGN: Multicenter retrospective cohort study. SETTING: Two tertiary academic spine centers. PATIENTS: Consecutive patients, aged 18 years or older, with EMG-confirmed lumbosacral radiculopathy. INTERVENTIONS: TFESI with a particulate or nonparticulate steroid to treat radicular pain within 6 months of EMG. MAIN OUTCOME MEASURES: The primary outcome was the proportion of patients with ≥50% pain reduction on the numerical rating scale after TFESI. Secondary outcomes included mean numerical rating scale score reduction and number of repeat TFESIs. Short-term (<30 days) and intermediate (≥30 days) outcomes were compared between patients who received a TFESI with a particulate versus nonparticulate steroid. RESULTS: Seventy-eight patients, with an age ± standard deviation of 56 ± 16 years and a mean symptom duration of 49 ± 71 months, were included. Forty-one patients (52%) received dexamethasone, 23 (30%) received triamcinolone, and 14 (18%) received betamethasone. There was no statistically significant difference in the proportion of patients who reported ≥50% pain reduction between the particulate and nonparticulate groups at short-term follow-up (35%; 95% confidence interval [CI], 21-51 versus 28%; 95% CI, 13-43) or at intermediate follow-up (40%; 95% CI, 21-59 versus 39%; 95% CI, 19-59). There was no difference in the mean number of injections administered between groups at intermediate follow-up (P = .26). CONCLUSIONS: This study demonstrates no significant differences in pain reduction or the number of repeat injections with particulate compared with nonparticulate transforaminal epidural steroid injection in patients with EMG-confirmed painful lumbosacral radiculopathy. These findings suggest a new population for whom nonparticulate steroid appears to be an appropriate first-line therapy, although confirmation with a randomized study is needed. LEVEL OF EVIDENCE: III.

Unusual Electromyographic Findings Associated With Colchicine Neuromyopathy: A Case Report.

An 83-year-old man with multiple medical problems, including gout, pseudogout, and renal insufficiency, presented with more than a year of proximal weakness. He had an extensive previous medical workup, including a normal creatinine kinase. His weakness persisted despite endurance and strength training. Electrodiagnostic findings were consistent with a myopathy, although without abnormal spontaneous activity and a length-dependent neuropathy. On the basis of these findings, colchicine was discontinued. The patient experienced marked symptomatic improvement within a week. Myopathies with neuropathies may be found with the use of colchicine. This case was unusual because of the absence of abnormal spontaneous activity and increased creatinine kinase, as typically reported with colchicine myopathy. LEVEL OF EVIDENCE: V.

Local, national, and service component cost variations in the management of low back pain: Considerations for the clinician.

In the past two decades, the cost associated with managing low back pain has increased significantly. Improved consciousness of how clinicians utilize resources when managing low back pain is necessary in the current economic climate. The goal of this review is to examine the component costs associated with managing low back pain and provide practical solutions for reducing healthcare costs. This is accomplished by utilizing examples from a major metropolitan area with several major academic institutions and private health care centers. It is clear that there is considerable local and national variation in the component costs of managing low back pain, including physician visits, imaging studies, medications, and therapy services. By being well informed about these variations in one's environment, clinicians and patients alike can make strides towards reducing the financial impact of low back pain. Investigation of the cost discrepancies for services within one's community of practice is important. Improved public access to both cost and outcomes data is needed.

Is There a Relationship Between Body Mass Index and Fluoroscopy Time During Sacroiliac Joint Injection? A Multicenter Cohort Study.

OBJECTIVE: To determine the relationship between BMI and fluoroscopy time during intra-articular sacroiliac joint (SIJ) injections performed for a pain indication. DESIGN: Multicenter retrospective cohort study. SETTING: Three academic, outpatient pain treatment centers. SUBJECTS: Patients who underwent fluoroscopy guided SIJ injection with encounter data regarding fluoroscopy time during the procedure and body mass index (BMI). MAIN OUTCOME MEASURE: Median and 25-75% Interquartile Range (IQR) fluoroscopy time. RESULTS: 459 SIJ injections (350 patients) were included in this study. Patients had a median age of 57 (IQR 44, 70) years, and 72% were female. The median BMI in the normal weight, overweight, and obese groups were 23 (IQR 21, 24), 27 (IQR 26, 29), and 35 (IQR 32, 40), respectively. There was no significant difference in the median fluoroscopy time recorded between these BMI classes (p = 0.45). First-time SIJ injection (p = 0.53), bilateral injection (p = 0.30), trainee involvement (p = 0.47), and new trainee involvement (trainee participation during the first 2 months of the academic year) (p = 0.85) were not associated with increased fluoroscopy time for any of the three BMI categories. CONCLUSIONS: Fluoroscopy time during sacroiliac joint injection is not increased in patients who are overweight or obese, regardless of whether a first-time sacroiliac joint injection was performed, bilateral injections were performed, a trainee was involved, or a new trainee was involved.

The Motivational Influence of Milestone Times on 10-km Running Performance.

To date, little research has been conducted to evaluate the potentially motivating effect of completing a race at a specific "milestone" finishing time. As this is difficult to perform in a laboratory setting, we examined 10-km runners from a large cohort to see if they were more likely to complete a race before rather than after a set milestone time (40:00, 45:00, and 50:00). Frequency distributions for finishers of each sex were created in 30-second time groups, with ideal normal distributions modeled based on this data. The actual time group frequencies were compared to the "expected" values from the modeled normal distributions. We included time groups that contained at least 1,000 finishers, thus were constrained to 36:00 - 52:00 for men and 43:30 to 52:00 for women. A total of 180,731 men and 53,047 women were included in the analysis. Men showed significant positive deviations (more finishers than expected) in the 39:30-40:00, 44:30-45:00, and 48:30-50:00 time groups (3 groups); they showed significant negative deviations only at 40:00-40:30 and 50:00-50:30. Women only showed significant positive time group deviations from 48:30-50:00 (1 group) with no significant negative deviations. In conclusion, despite the relatively arbitrary nature of milestones, they appear to exert a motivational influence on 10-km runners.

Outcomes of Inpatient Rehabilitation in Patients With Simultaneous Bilateral Total Knee Arthroplasty.

BACKGROUND: The number of total knee arthroplasty (TKA) procedures performed in the United States is increasing each year, and the number of bilateral TKA procedures has also increased during the past 2 decades. However, few studies in the literature have investigated the rehabilitation outcomes of patients who undergo bilateral TKA. This study was performed to provide information on the benefits and role of inpatient rehabilitation for patients after bilateral TKA. OBJECTIVE: To investigate the functional outcomes, complications, and transfer rates of patients in the inpatient rehabilitation setting who undergo simultaneous bilateral TKA. DESIGN: Retrospective cohort study. SETTING: Freestanding inpatient rehabilitation hospital. PATIENTS: Ninety-four patients admitted to an inpatient rehabilitation hospital after simultaneous bilateral TKA from 2008-2013. METHODS: Retrospective chart review of demographic, clinical, and functional data for patients admitted to inpatient rehabilitation after simultaneous bilateral TKA. MAIN OUTCOME MEASURES: Length of stay, admission and discharge Functional Independence Measure (FIM), and FIM efficiency. RESULTS: The study included 27 male (28.7%) and 67 female (71.3%) patients aged 42.0-86.9 years, with a mean of 65.6 ± 10.2 years. Mean length of time between surgery and admission to inpatient rehabilitation was 4.5 ± 3.3 days. Mean length of stay in rehabilitation was 11.7 ± 4.2 days. Mean admission and discharge FIM scores were 87.3 ± 11.7 and 113.4 ± 4.8, respectively, with a mean FIM gain of 26.1 ± 10.5. The mean FIM efficiency was 2.33 ± 0.84. Eight patients required transfer to an acute care hospital. Complications leading to transfer to acute care facilities included sepsis, cardiac arrhythmias, knee dislocation, and suspected small bowel obstruction. Eighty-eight patients were discharged home, 4 patients were discharged to skilled nursing facilities, and 2 patients were transferred to an acute care hospital and did not return to the inpatient rehabilitation hospital. CONCLUSIONS: After undergoing simultaneous bilateral TKA, patients demonstrate functional gains when admitted to inpatient rehabilitation facilities based on FIM gains and FIM efficiency scores; 8.5% of patients in this cohort required transfer to an acute care facility as a result of complications during inpatient rehabilitation, and 93.6% of patients were discharged home.

Does Electrodiagnostic Confirmation of Radiculopathy Predict Pain Reduction after Transforaminal Epidural Steroid Injection? A Multicenter Study.

OBJECTIVE: Minimal definitive literature identifies patients with radicular pain who would benefit most from epidural steroid injection (ESI). This study investigated if electromyographic (EMG) confirmation of radiculopathy with active or chronic denervation predicts a positive treatment outcome following ESI. DESIGN: Longitudinal cohort study of adults who underwent EMG and subsequent transforaminal ESI within 6 months. The proportion of individuals who experienced >50% pain relief and mean change in daily morphine equivalents (DME) were calculated. RESULTS: 170 individuals with respective mean (Standard Deviation) age and duration of symptoms of 55 (15) years and 36 (56) months were included. Mean time to <30 day and >30 day follow-up post-injection were 18 (6) and 99 (130) days, respectively. At >30 day follow-up, a larger proportion of EMG-confirmed individuals (37.7%) reported >50% pain reduction compared to EMG-negative individuals (17.8%) (p=0.03). This was significant for lumbosacral (40% vs. 15%, p=0.01) but not cervical symptoms (p>0.05). Mean decrease in DME at long-term follow-up in EMG-confirmed compared to EMG-negative individuals trended toward significance (-4 vs. -1, p=0.11). There was no significant relationship between myotomal spontaneous activity and pain or opioid use. CONCLUSIONS: Needle EMG predicts long-term pain reduction from transforaminal ESI in patients with lumbosacral radiculopathy, regardless of the presence of active denervation.

Increased FGF-2 secretion and ability to support neurite outgrowth by astrocytes cultured on polyamide nanofibrillar matrices.

An electrospun nonwoven matrix of polyamide nanofibers was employed as a new model for the capillary basement membrane at the blood-brain barrier (BBB). The basement membrane separates astrocytes from endothelial cells and is associated with growth factors, such as fibroblast growth factor-2 (FGF-2). FGF-2 is produced by astrocytes and induces specialized functions in endothelial cells, but also has actions on astrocytes. To investigate potential autocrine actions of FGF-2 at the BBB, astrocytes were cultured on unmodified nanofibers or nanofibers covalently modified with FGF-2. The former assumed an in vivo-like stellate morphology that was enhanced in the presence of cross-linked FGF-2. Furthermore, astrocyte monolayers established on unmodified nanofibers were more permissive for neurite outgrowth when cultured with an overlay of neurons than similar monolayers established on standard tissue culture surfaces, while astrocytes cultured on FGF-2-modifed nanofibers were yet more permissive. The observed differences were due in part to progressively increasing amounts of FGF-2 secreted by the astrocytes into the medium; hence FGF-2 increases its own expression in astrocytes to modulate astrocyte-neuron interactions. Soluble FGF-2 was unable to replicate the effects of cross-linked FGF-2. Nanofibers alone up-regulated FGF-2, albeit to a lesser extent than nanofibers covalently modified with FGF-2. These results underscore the importance of both surface topography and growth factor presentation on cellular function. Moreover, these results indicate that FGF-2-modified nanofibrillar scaffolds may demonstrate utility in tissue engineering applications for replacement and regeneration of lost tissue following central nervous system (CNS) injury or disease.

Covalently attached FGF-2 to three-dimensional polyamide nanofibrillar surfaces demonstrates enhanced biological stability and activity.

Activation of fibroblast growth factor receptors (FGFRs) requires the formation of a ternary complex between fibroblast growth factors (FGFs), FGFRs, and heparan sulfate proteoglycans, which are all located on the cell surface and the basement membrane (BM)/extracellular matrix (ECM). Heparan sulfate proteoglycans appear to stabilize FGFs by inhibiting the rapid degradation of FGFs normally observed in solution. Because of the pivotal role of FGFs in proliferative and developmental pathways, a number of recent studies have attempted to engineer microenvironments to stabilize growth factors for use in applications in tissue culture and regenerative medicine. In this communication, we demonstrate that covalent linkage of FGF-2 to nanofibrillar surfaces (defined as covalently bound FGF-2) composed of a network of polyamide nanofibers resulted in the maintenance of the biological efficacy of FGF-2 when stored dry for at least 6 months at 25 degrees C or 4 degrees C. Moreover, covalently bound FGF-2 was more potent than FGF-2 in solution when measured in cellular assays of proliferation and viability using a variety of cell types. Covalently bound FGF-2 also strongly activated FGFR, extracellular signal-regulated kinase (ERK1/2), and c-fos. Hence cell-signaling molecules can be incorporated into a synthetic nanofibrillar surface, providing a novel means to enhance their stability and biological activity.

Three-dimensional nanofibrillar surfaces covalently modified with tenascin-C-derived peptides enhance neuronal growth in vitro.

Current methods to promote growth of cultured neurons use two-dimensional (2D) glass or polystyrene surfaces coated with a charged molecule (e.g. poly-L-lysine (PLL)) or an isolated extracellular matrix (ECM) protein (e.g. laminin-1). However, these 2D surfaces represent a poor topological approximation of the three-dimensional (3D) architecture of the assembled ECM that regulates neuronal growth in vivo. Here we report on the development of a new 3D synthetic nanofibrillar surface for the culture of neurons. This nanofibrillar surface is composed of polyamide nanofibers whose organization mimics the porosity and geometry of the ECM. Neuronal adhesion and neurite outgrowth from cerebellar granule, cerebral cortical, hippocampal, motor, and dorsal root ganglion neurons were similar on nanofibers and PLL-coated glass coverslips; however, neurite generation was increased. Moreover, covalent modification of the nanofibers with neuroactive peptides derived from human tenascin-C significantly enhanced the ability of the nanofibers to facilitate neuronal attachment, neurite generation, and neurite extension in vitro. Hence the 3D nanofibrillar surface provides a physically and chemically stabile cell culture surface for neurons and, potentially, an exciting new opportunity for the development of peptide-modified matrices for use in strategies designed to encourage axonal regrowth following central nervous system injury.