Diagnostic performance of MRA in abduction and external rotation position in the detection of glenoid labral lesions: a systematic review and meta-analysis.

OBJECTIVE: To compare the diagnostic performance of direct magnetic resonance arthrography (MRA) for labral lesions during conventional, abduction and external rotation (ABER), conventional plus abduction, and external rotation (ABER) positioning by using a systematic review and meta-analysis. MATERIALS AND METHODS: A comprehensive literature search was performed on the two main concepts of magnetic resonance arthrography: extremity position and labral lesions. Inclusion criteria consisted of original studies that assessed the diagnostic accuracy of MR arthrography in ABER and conventional position alone or combined for the diagnosis of labral lesions by using surgical findings as the reference standard. Meta-analyses were performed that compared MR arthrography during conventional positioning, ABER, and conventional plus ABER positioning. RESULTS: Nine studies met the inclusion and exclusion criteria. A total of 733, 504, and 313 lesions assessed by conventional MRA, ABER MRA, and conventional plus ABER MRA, respectively, were included in our analysis. Pooled sensitivities of MRA in conventional, ABER, and conventional plus ABER position for labral tear diagnosis were 81.5%, 81.6%, and 95.7%, respectively. Pooled specificities of MRA in conventional, ABER, and conventional plus ABER position for labral tear diagnosis were 88.8%, 85.6%, and 94.5%, respectively. Summary receiver operator characteristic (ROC) curve demonstrated improved accuracy of conventional plus ABER MRA compared with conventional MRA or ABER MRA with the area under the curve (AUC) of 0.99, 0.90, and 0.88, respectively. CONCLUSION: Conventional plus ABER MRA showed increased diagnostic accuracy compared to both ABER MRA and conventional MRA alone in the diagnosis of labral lesions.

Review of human supraspinatus tendon mechanics. Part II: tendon healing response and characterization of tendon health.

Overuse injuries of the rotator cuff, particularly of the supraspinatus tendon (SST), are highly prevalent and debilitating in work, sport, and daily activities. Despite the clinical significance of these injuries, there remains a large degree of uncertainty regarding the pathophysiology of injury, optimal methods of nonoperative and operative repair, and how to adequately assess tendon injury and healing. The tendon response to fatigue damage resulting from overuse is different from that of acute rupture and results in either an adaptive (healing) or a maladaptive (degenerative) response. Factors associated with the degenerative response include increasing age, smoking, hypercholesterolemia, biological sex (variable by tendon), diabetes mellitus, and excessive load post fatigue damage. After injury, the average healing rate of tendon is approximately 1% per day and may be significantly influenced by biologic sex (females have lower collagen synthesis rates) and excessive load after damage. Although magnetic resonance imaging (MRI) is considered the gold standard in assessing acute tears as well as tendinopathic change in the SST, ultrasonography has proven to be a valuable tool to measure tendinopathic change in real time. Ultrasonography can determine multiple mechanical and structural parameters of the SST that are altered in fatigue loading. Thus, ultrasonography may be utilized to understand how these parameters change in response to SST overuse, and may aid in determining the activity level that places the SST at greater risk of rupture.

Review of human supraspinatus tendon mechanics. Part I: fatigue damage accumulation and failure.

Repetitive stress injuries to the rotator cuff, and particularly the supraspinatus tendon (SST), are highly prevalent and debilitating. These injuries typically occur through the application of cyclic load below the threshold necessary to cause acute tears, leading to accumulation of incremental damage that exceeds the body's ability to heal, resulting in decreased mechanical strength and increased risk of frank rupture at lower loads. Consistent progression of fatigue damage across multiple model systems suggests a generalized tendon response to overuse. This finding may allow for interventions before gross injury of the SST occurs. Further research into the human SST response to fatigue loading is necessary to characterize the fatigue life of the tendon, which will help determine the frequency, duration, and magnitude of load spectra the SST may experience before injury. Future studies may allow in vivo SST strain analysis during specific activities, generation of a human SST stress-cycle curve, and characterization of damage and repair related to repetitive tasks.

Radiological Society of North America/Quantitative Imaging Biomarker Alliance Shear Wave Speed Bias Quantification in Elastic and Viscoelastic Phantoms.

OBJECTIVES: To quantify the bias of shear wave speed (SWS) measurements between different commercial ultrasonic shear elasticity systems and a magnetic resonance elastography (MRE) system in elastic and viscoelastic phantoms. METHODS: Two elastic phantoms, representing healthy through fibrotic liver, were measured with 5 different ultrasound platforms, and 3 viscoelastic phantoms, representing healthy through fibrotic liver tissue, were measured with 12 different ultrasound platforms. Measurements were performed with different systems at different sites, at 3 focal depths, and with different appraisers. The SWS bias across the systems was quantified as a function of the system, site, focal depth, and appraiser. A single MRE research system was also used to characterize these phantoms using discrete frequencies from 60 to 500 Hz. RESULTS: The SWS from different systems had mean difference 95% confidence intervals of ±0.145 m/s (±9.6%) across both elastic phantoms and ± 0.340 m/s (±15.3%) across the viscoelastic phantoms. The focal depth and appraiser were less significant sources of SWS variability than the system and site. Magnetic resonance elastography best matched the ultrasonic SWS in the viscoelastic phantoms using a 140 Hz source but had a - 0.27 ± 0.027-m/s (-12.2% ± 1.2%) bias when using the clinically implemented 60-Hz vibration source. CONCLUSIONS: Shear wave speed reconstruction across different manufacturer systems is more consistent in elastic than viscoelastic phantoms, with a mean difference bias of < ±10% in all cases. Magnetic resonance elastographic measurements in the elastic and viscoelastic phantoms best match the ultrasound systems with a 140-Hz excitation but have a significant negative bias operating at 60 Hz. This study establishes a foundation for meaningful comparison of SWS measurements made with different platforms.

What Is the Survivorship After Hip Arthroscopy for Femoroacetabular Impingement? A Large-database Study.

BACKGROUND: Patients with femoroacetabular impingement (FAI) may experience lasting clinical improvement after hip arthroscopy; however, some patients will still eventually undergo early conversion to THA due to unresolved symptoms and progression of arthritis. However, the risk of this has been only incompletely characterized in prior studies. QUESTIONS/PURPOSES: Using a large healthcare claims database over a 5-year period (2011-2016), we asked: (1) What is the survivorship free from THA after arthroscopic osteoplasty performed for FAI? (2) What identifiable demographic factors and patient characteristics are associated with early conversion to THA after hip arthroscopy performed for FAI? METHODS: We included all patients who underwent hip arthroscopy for FAI, between the ages of 12 years and 63 years, with 3 months of claims data before hip arthroscopy and minimum 2-year follow-up. A total of 4730 hip arthroscopy patients from 2011 to 2014 were retrieved from a US commercial claims database. Hip arthroscopy incidence doubled over time from 1.2 to 2.1 persons per 100,000. Temporal trends, patient demographics, diagnoses at time of arthroscopy, and patient comorbidities were retrieved and logistic regression performed. Survivorship analysis on 11,323 patients (lifting the 2-year follow-up requirement) was also performed to identify independent variables associated with early risk of conversion to THA. RESULTS: In patients undergoing hip arthroscopy for FAI, the overall proportion of conversion to THA within 2 years after hip arthroscopy was 7% (338 of 4730). After controlling for confounding variables such as sex, obesity, and depression, we found the following were independently associated with increased odds of conversion to THA: older age (odds ratio 1.08 [95% CI 1.01 to 1.10]; p < 0.001), osteoarthritis (OR 2.91 [95% CI 2.27 to 3.77]; p < 0.001), joint inflammation (OR 1.89 [95% CI 1.16 to 3.09]; p = 0.01), and a history of opioid use (OR 2.17 [95% CI 1.69 to 2.79]; p < 0.001). Survivorship analysis similarly revealed that older age (hazard ratio 1.08 [95% CI 1.07 to 1.09]; p < 0.001), osteoarthritis (HR 2.53 [95% CI 2.13 to 3.01]; p < 0.001), joint inflammation (HR 1.53 [95% CI 1.10 to 2.11]; p = 0.01), a history of opioid use (HR 2.02 [95% CI 1.71 to 2.38]; p < 0.001), and smoking (HR 1.55 [95% CI 1.14 to 2.11]; p = 0.005), were independently associated with increased odds of conversion to THA within 2 years after hip arthroscopy for FAI. CONCLUSIONS: Although the findings of this study are limited and should not be taken in isolation, patients with FAI who are older, carry diagnoses of inflammatory or degenerative articular disease, or who use opioids or smoke should be counseled about a potentially increased risk of undergoing early conversion to THA after hip arthroscopy. Future studies to further examine the effect of these diagnoses in prospectively collected cohorts, incorporating radiographic and patient-reported outcome measures, are needed. LEVEL OF EVIDENCE: Level III, prognostic study.

Generation and characterization of mice with mesenchyme-specific deletion of the entire ESET histone methyltransferase protein.

ESET protein (also known as SETDB1) catalyzes methylation of histone H3 at lysine 9 (H3-K9). In addition to the full-length transcript, mouse ESET gene also gives rise to alternative spicing variants encoding truncated proteins capable of retaining interaction with other epigenetic enzymes. To completely eliminate full-length ESET and its splicing variants, we have generated a conditional ESET allele with exon 4 flanked by two loxP sites for Cre-mediated DNA deletion and downstream frame-shift mutation of the entire coding region. Mating with Prx1-Cre mice and analysis of the resultant embryos revealed that mesenchyme-specific knockout of exon 4 completely eliminates full-length ESET and its truncated protein products, leading to profound defects in both the flat bones and long bones, ectopic hypertrophy of growth plate chondrocytes and downregulation of Indian hedgehog protein. In addition, exon 4 deletion results in reduced thickness of articular cartilage in E17.5 embryos, whereas deletion of exons 15-16 fails to do so. These findings offer us a useful tool to further study epigenetic regulation in a truly ESET-null background, and demonstrate that ESET plays a critical role in the control of chondrocyte hypertrophy and skeletal development.

Pathologies of the shoulder and elbow affecting the overhead throwing athlete.

The overhead-throwing athlete is susceptible to a variety of predictable disease entities affecting the shoulder and elbow. While the pathophysiology and nomenclature of these diseases are ubiquitous throughout the clinical literature, this information is sparse within the radiology domain. We provide a comprehensive review of these unique injuries with accompanying imaging features in an effort to enhance the role of the radiologist during the management of the overhead thrower. When appropriately recognized and described, the imaging features aid in establishing a diagnosis and ultimately the implementation of appropriate clinical management.

Is there evidence that the outcomes of primary anatomic and reverse shoulder arthroplasty are getting better?

PURPOSE: Have the results of shoulder arthroplasty got better over the last two decades? To answer this question, we sought published evidence that the patient-reported outcomes and re-operation rates have improved in reports of more recently performed anatomic (TSA) and reverse (RSA) total shoulder arthroplasties. METHODS: We analyzed the arthroplasty results among studies published from 1990 to 2015, adjusting for the fact that the different publications presented patient groups with different combinations of diagnoses, used various outcome scales, and had different lengths of follow-up. RESULTS: The adjusted clinical outcomes (p = 0.048), but not the revision rates (p = 0.3), were significantly better for articles reporting more recent TSA procedures. Neither the clinical outcomes (p = 0.9) nor the revision rates (p = 0.4) were significantly better in articles reporting more recent RSA surgeries. CONCLUSIONS: Better evidence from reports with greater detail will be necessary to show that patients are realizing progressively better outcomes from shoulder arthroplasty. LEVEL OF EVIDENCE: Level IV.

Impaction autografting: bone-preserving, secure fixation of a standard humeral component.

BACKGROUND: When fixed with bone ingrowth, a tight diaphyseal press fit, or cement, the humeral component of a shoulder arthroplasty may present problems of malposition, stress shielding, or periprosthetic fracture or difficulty with removal at revision arthroplasty. We have avoided the need for these fixation methods by using impaction cancellous autografting of the humeral stem, minimizing contact between the prosthetic stem and the humeral cortex. This study presents the radiographic survivorship of impaction-autografted humeral implants using component subsidence as the primary endpoint. METHODS: We reviewed 286 primary anatomic shoulder arthroplasties having an average follow-up of 4.9 ± 2.7 years. Initial postoperative radiographs and minimum 2-year follow-up radiographs were evaluated by 3 observers to assess subsidence. RESULTS: Two different implants (Humeral Replacement Prosthesis [HRP] and Global Advantage prosthesis) were used. Of 286 stems, 267 (93.4%) had not subsided. The Global Advantage prosthesis had a subsidence-free survival rate of 98.5% at 5 years. The stiffer-stemmed HRP used early during the study had a higher rate of subsidence compared with the currently used Global Advantage stem (hazard ratio, 5.6; P = .001). Radiolucent lines of 2 mm or greater were less common for the Global Advantage prosthesis than for the HRP in each of 7 zones (P < .001). Total shoulder arthroplasty was associated with a higher rate of subsidence compared with hemiarthroplasty (hazard ratio, 2.6; P = .12). CONCLUSIONS: Impaction autografting provides a secure, durable, bone-preserving means of humeral component fixation in anatomic shoulder arthroplasty.

Management of intraoperative posterior decentering in shoulder arthroplasty using anteriorly eccentric humeral head components.

BACKGROUND: Posterior humeral decentering presents a challenge in glenohumeral arthroplasty. Soft tissue releases and osteophyte resection can lead to intraoperative decentering not evident preoperatively. Inferior outcomes result if decentering is not addressed as a part of the arthroplasty. When there is >50% posterior subluxation of the humeral head on passive elevation of the arm at surgery, we have used an anteriorly eccentric humeral head component to improve centering of the humeral articular surface on the glenoid. METHODS: We reviewed the 2-year outcomes for 33 shoulder arthroplasties in which anteriorly eccentric humeral heads were used to manage posterior decentering identified at surgery. Rotator interval plication was performed in 16 cases as an adjunctive stabilizing procedure. Shoulders were evaluated preoperatively and postoperatively with the Simple Shoulder Test (SST). Radiographic centering was characterized before surgery and at follow-up on standardized axillary radiographs with the arm held in a position of functional elevation. RESULTS: With the anteriorly eccentric head component, preoperative radiographic humeral decentering was reduced from 10.4% ± 7.9% to 0.9% ± 2.3% postoperatively (P < .001). SST scores improved from 4.8 ± 2.3 to 10.0 ± 2.3 (P < .001). Preoperative posterior humeral head decentering did not correlate with preoperative glenoid version. Glenoid retroversion was 19.8° ± 8.9° preoperatively and 15.5° ± 7.5° postoperatively. CONCLUSIONS: Posterior decentering identified at surgery when standard trial components are in place can be addressed by replacing the anatomic humeral head with an anteriorly eccentric humeral head component.

Determination of steroid injection sites using lidocaine test in adhesive capsulitis: A prospective randomized clinical trial.

BACKGROUND: To validate the usefulness of subacromial bursa lidocaine for determination of the therapeutic steroid injection site in patients with adhesive capsulitis METHODS: Ninety-two patients with adhesive capsulitis were randomly divided into the LC (lidocaine test) group (n = 46), in which LC injection was performed at the subacromial bursa prior to therapeutic steroid injection, and GH (glenohumeral) group (n = 46), in which the steroid was injected into the GH. Patients in the LC group received steroid injection at the subacromial bursa or GH according to the result of the LC. Both groups underwent the same exercise protocol. Improvement of the shoulder pain was checked at 2 weeks and 3 months postinjection and expressed on an ordinal scale. Passive range of motion was recorded preinjection, and 2 weeks and 3 months postinjection. RESULTS: Two weeks postinjection, 37 patients expressed "much improved" and 7 patients expressed "slightly improved" pain levels in the LC group, whereas 18 patients each expressed "much improved" and "slightly improved" pain levels in the GH group, which was significantly different (p < 0.01). This difference was maintained 3 months postinjection (p < 0.01). Passive range of motion in all directions improved significantly 3 months postinjection in both the LC and GH groups (p < 0.01). However, there was no significant difference between the LC and GH groups. CONCLUSIONS: We found that subacromial lidocaine injection prior to steroid injection resulted in better improvement of pain than conventional GH injection for patients with adhesive capsulitis.

Effect of Age and Body Mass Index on Time to Advanced Imaging and Surgery in Young Athletes With Anterior Cruciate Ligament Injury.

Background: In young athletes with anterior cruciate ligament (ACL) injury, increased times from injury to magnetic resonance imaging (MRI) and injury to surgery can lead to the accrual of new injuries over time. Purpose: To determine the patient characteristics associated with differences in timing between injury, MRI, and surgery in young athletes with ACL tears. Study Design: Case-control study; Level of evidence, 3. Methods: We reviewed the electronic medical records of patients aged 13 to 25 years who underwent isolated primary ACL reconstruction between January 2017 and June 2020 at a single orthopaedic surgery department. The times from injury to MRI, MRI to surgery, and injury to surgery were documented. Patient demographic data (age, sex, body mass index [BMI], race and ethnicity, and insurance type) were recorded. Multivariable analysis was used to determine if any patient characteristic had a significant association with increased time to MRI or surgery. Results: A total of 369 patients (mean age, 18.0 years; 56% female) were included. Both age and BMI were found to be significantly associated with timing of care while holding all other predictors constant. For every 1-year increase in patient age, time from injury to MRI increased by 9.6 days (95% CI, 1.8-17.4 days; P = .02), time from MRI to surgery increased by 7.4 days (95% CI, 4.4-10.5 days; P < .001), and time from injury to surgery increased by 17.0 days (95% CI, 8.4-25.6 days; P < .001). Compared with patients with normal BMI, overweight patients (BMI range, 25-29.9 kg/m2) had an MRI-to-surgery time that was on average 37.2 days (95% CI, 11.7-62.7 days; P < .004) longer and an injury to surgery time that was on average 71.8 days (95% CI, 0.5-143.0 days; P = .048) longer. Obese patients (BMI ≥30 kg/m2) did not demonstrate a significant relationship with the studied time intervals. Conclusion: Increasing age and elevated BMI were found to be associated with increased time to MRI and surgical care in young athletes with ACL injuries.

Limited Return to Preinjury Performance in NCAA Division I American Football Players With Hamstring Injuries.

Background: Hamstring strains are common among elite athletes, but their effect on return to the same level of play in American football has been incompletely characterized. Purpose: Data on National Collegiate Athletics Association Division I college football players with acute hamstring strains were gathered to identify the effects these injuries have on both return to play and athletic performance regarding velocity, workload, and acceleration. Study Design: Case Series; Level of evidence, 4. Methods: Injury data for a single Division I football team were prospectively recorded over a 4-year period. Players wore global navigation satellite system and local positioning system (GNSS/LPS) devices to record movement data in practices and games. The practice and game data were cross-referenced to evaluate players with isolated acute hamstring strains. Comparisons were made regarding players' pre- and postinjury ability to maintain high velocity (>12 mph [19.3 kph]), maximal velocity, triaxial acceleration, and inertial movement analysis (IMA). There were 58 hamstring injuries in 44 players, of which 25 injuries from 20 players had GNSS/LPS data. Results: Players were able to return to play from all 25 injury incidences at a mean of 9.2 days. At the final mean follow-up of 425 days, only 4 players had reached preinjury function in all measurements; 12 players were able to return in 2 of the 4 metrics; and only 8 players reached their preinjury ability to maintain high velocity. For those who did not achieve this metric, there was a significant difference between pre- and postinjury values (722 vs 442 m; P = .016). A total of 14 players were able to regain their IMA. Players who returned to prior velocity or acceleration metrics did so at a mean of 163 days across all metrics. Conclusion: While players may be able to return to play after hamstring strain, many players do not reach preinjury levels of acceleration or velocity, even after 13.5 months. Further studies are needed to confirm these findings, assess clinical relevance on imaging performance, and improve hamstring injury prevention and rehabilitation.

Anterior cruciate ligament reconstruction in patients aged > 40 years: a case-control study.

PURPOSE: To determine the outcomes of isolated anterior cruciate ligament (ACL) reconstruction in physically active patients aged > 40 years, and to compare these results with those of a younger patient cohort who underwent the same procedure. METHODS: A retrospective review was performed on all patients aged > 40 years who underwent ACL reconstruction between 2000 and 2008. A consecutive series of patients aged ≤ 25 years who underwent the same procedure during this same time period were selected as a control group. Age, sex, graft type, concomitant injuries, complications, and a validated outcome measure (Lysholm Knee Scoring Scale) were assessed at final follow-up. RESULTS: Forty-six patients (average age, 44.9 years; 28 men, 18 women) in the older group were identified and compared with 48 patients (average age, 21 years; 23 men, 25 women) in the younger group, with an average follow-up period of 5.4 and 5.1 years, respectively. There was no statistically significant difference between the groups in terms of associated injuries. The older group had a higher degree of cartilage degeneration (P = 0.0001). Lysholm scores averaged 90.3 in the older cohort compared with 88.7 in the younger cohort, with no statistical difference between groups. CONCLUSION: The older patients had outcomes comparable with the younger patients. Age alone should not exclude ACL-deficient patients from undergoing reconstructive surgery.

Effect of Delayed Anterior Cruciate Ligament Reconstruction on Repair of Concomitant Medial Meniscus Tears in Young Athletes.

BACKGROUND: Delayed anterior cruciate ligament (ACL) reconstruction (ACLR) is associated with an increased risk of meniscal injury. Limited data are available regarding the relationship between surgical delay and meniscal repairability in the setting of ACLR in young patients. PURPOSE: To determine whether time from ACL injury to primary ACLR was associated with the incidence of medial and/or lateral meniscal repair in young athletes who underwent meniscal treatment at the time of ACLR. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Records were retrospectively reviewed for patients aged 13 to 25 years who underwent primary ACLR between January 2017 and June 2020 by surgeons from a single academic orthopaedic surgery department. Demographic data were collected, and operative reports were reviewed to document all concomitant pathologies and procedures. Univariable and multivariable logistic regression analyses were used to determine factors associated with meniscal repair, including time elapsed from ACL injury to surgery. RESULTS: Concomitant meniscal tears were identified and treated in 243 of 427 patients; their mean age was 17.9 ± 3.3 years, and approximately half (47.7%) of patients were female. There were 144 (59.3%) medial tears treated and 164 (67.5%) lateral tears treated; 65 (26.7%) patients had both medial and lateral tears treated. Median time from ACL injury to ACLR was 2.4 months (interquartile range, 1.4-4.7 months). Adjusted univariate analysis showed a statistically significant correlation between medial meniscal repair and time to surgery, with a 7% decreased incidence of medial meniscal repair per month elapsed between injury and surgery (odds ratio, 0.93 per month; 95% CI, 0.89-0.98; P = .006). No similar relationship was found between lateral meniscal repair and time to surgery (odds ratio, 1.02; 95% CI, 0.99-1.06; P = .24). CONCLUSION: In the setting of concomitant ACL and meniscal injuries, surgical delay decreased the incidence of medial meniscal repair in young athletes by 7% per month from time of injury.

Effect of Increased Time to Surgery on the Ability of MRI to Rule Out Medial Meniscal Tears in Young Athletes With ACL Injury.

Background: The prevalence of meniscal tears in patients with anterior cruciate ligament (ACL) injury increases with extended time between injury and ACL reconstruction. Purpose/Hypothesis: The purpose of this study was to determine if there is a relationship between time from magnetic resonance imaging (MRI) to ACL reconstruction and the predictive value of MRI to diagnose meniscal tears in the young active population. It was hypothesized that increased time between MRI and ACL reconstruction would lead to a decrease in the negative predictive value of MRI in diagnosing meniscal tears, as more injuries may accrue over time in the ACL-deficient knee. Study Design: Case series; Level of evidence, 4. Methods: Included were patients aged 13 to 25 years at the authors' institution who underwent primary ACL reconstruction from January 2017 to June 2020. Time from MRI to surgery as well as descriptions of medial and lateral meniscal tears on both MRI and operative reports were documented. Time from MRI to surgery was divided into 4 intervals: 0 to 6 weeks, >6 weeks to 3 months, >3 to 6 months, and beyond 6 months. Multivariable analysis was used to determine the positive and negative predictive values of MRI in diagnosing a meniscal tear as compared with arthroscopic findings. Results: A total of 432 patients were included with a mean age of 17.9 ± 3.4 years. The mean time from MRI to surgery was 70.5 ± 98 days. There was a significant decrease in the negative predictive value of MRI to identify a medial meniscal tear in patients who underwent ACL reconstruction >6 months after imaging (odds ratio, 0.16 [95% CI, 0.05-0.53]; P = .003). This same relationship was not shown for lateral meniscal tears, nor was any other predictor significant. Conclusion: The utility of MRI to rule out a medial meniscal tear significantly diminished in the young athletic population when >6 months passed between MRI and ACL reconstruction. These data suggest these tears occur between the time of the MRI and surgery and that the medial meniscus is more susceptible than the lateral meniscus to new injury once the ACL has torn.

Fabrication and evaluation of biomimetic-synthetic nanofibrous composites for soft tissue regeneration.

Electrospun scaffolds hold promise for the regeneration of dense connective tissues, given their nanoscale topographies, provision of directional cues for infiltrating cells and versatile composition. Synthetic slow-degrading scaffolds provide long-term mechanical support and nanoscale instructional cues; however, these scaffolds suffer from a poor infiltration rate. Alternatively, nanofibrous constructs formed from natural biomimetic materials (such as collagen) rapidly infiltrate but provide little mechanical support. To take advantage of the positive features of these constructs, we have developed a composite scaffold consisting in both a biomimetic fiber fraction (i.e., Type I collagen nanofibers) together with a traditional synthetic (i.e., poly-[ε-caprolactone], PCL) fiber fraction. We hypothesize that inclusion of biomimetic elements will improve initial cell adhesion and eventual scaffold infiltration, whereas the synthetic elements will provide controlled and long-term mechanical support. We have developed a method of forming and crosslinking collagen nanofibers by using the natural crosslinking agent genipin (GP). Further, we have formed composites from collagen and PCL and evaluated the long-term performance of these scaffolds when seeded with mesenchymal stem cells. Our results demonstrate that GP crosslinking is cytocompatible and generates stable nanofibrous type I collagen constructs. Composites with varying fractions of the biomimetic and synthetic fiber families are formed and retain their collagen fiber fractions during in vitro culture. However, at the maximum collagen fiber fractions (20%), cell ingress is limited compared with pure PCL scaffolds. These results provide a new foundation for the development and optimization of biomimetic/synthetic nanofibrous composites for in vivo tissue engineering.