Gravity-based patterning of osteogenic factors to preserve bone structure after osteochondral injury in a large animal model.

Chondral and osteochondral repair strategies are limited by adverse bony changes that occur after injury. Bone resorption can cause entire scaffolds, engineered tissues, or even endogenous repair tissues to subside below the cartilage surface. To address this translational issue, we fabricated thick-shelled poly(D,L-lactide-co-glycolide) microcapsules containing the pro-osteogenic agents triiodothyronine andß-glycerophosphate, and delivered these microcapsules in a large animal model of osteochondral injury to preserve bone structure. We demonstrate that the developed microcapsules rupturedin vitrounder increasing mechanical loads, and readily sink within a liquid solution, enabling gravity-based patterning along the osteochondral surface. In a large animal, these mechanically-activated microcapsules (MAMCs) were assessed through two different delivery strategies. Intra-articular injection of control MAMCs enabled fluorescent quantification of MAMC rupture and cargo release in a synovial joint setting over timein vivo. This joint-wide injection also confirmed that the MAMCs do not elicit an inflammatory response. In the contralateral hindlimbs, chondral defects were created, MAMCs were patternedin situ, and nanofracture (Nfx), a clinically utilized method to promote cartilage repair, was performed. The Nfx holes enabled marrow-derived stromal cells to enter the defect area and served as repeatable bone injury sites to monitor over time. Animals were evaluated one and two weeks after injection and surgery. Analysis of injected MAMCs showed that bioactive cargo was released in a controlled fashion over two weeks. A bone fluorochrome label injected at the time of surgery displayed maintenance of mineral labeling in the therapeutic group, but resorption in both control groups. Alkaline phosphatase (AP) staining at the osteochondral interface revealed higher AP activity in defects treated with therapeutic MAMCs. Overall, this study develops a gravity-based approach to pattern bioactive factors along the osteochondral interface, and applies this novel biofabrication strategy to preserve bone structure after osteochondral injury.

Investigating Patient-Level Radiation Exposure in Hand and Wrist Fracture Surgery.

BACKGROUND: Although occupational exposure to radiation has been previously studied in the hand surgery literature, there is a paucity of studies looking at radiation exposure to the patient during fluoroscopy-guided hand surgery. We aimed to describe the level of radiation experienced by patients undergoing common hand and wrist fracture fixation and to identify risk factors for increased radiation exposure. METHODS: We performed a retrospective review of patients at a single institution who underwent fracture fixation of the hand, wrist, or forearm requiring mini c-arm fluoroscopic guidance from 2016 to 2020. Data points collected included patient demographics, procedural details, and indicators of radiation exposure including dose-area product (DAP), total intraoperative images, and total fluoroscopy time. Effective dose (ED) was calculated using DAP, field size, and a previously established conversion factor. RESULTS: The final sample included 361 patients with an average age of 46 years. Procedures included fixation of forearm fractures (3.3%), distal radius fractures (35.7%), metacarpal fractures (30.8%), and phalangeal fractures (30.2%). The median number of intraoperative images acquired was 36, median total fluoroscopy time was 43 seconds, median DAP was 4.8 cGycm2, and median ED was 0.13 µSv. Distal (metacarpal and phalangeal) fractures required more intraoperative images and longer total fluoroscopy time (49 images, 61 seconds) compared with proximal (forearm and distal radius) fractures (39 images, 47 seconds) (images, P = 0.004; exposure time, P = 0.004). However, distal fractures had a lower average ED compared with proximal fractures (0.15 vs 0.19 µSv, P = 0.020). When compared with open procedures, percutaneous procedures had higher DAPs (8.8 vs 4.9 cGycm2, P < 0.001), higher ED (0.22 vs 0.15 µSv, P < 0.001), more intraoperative images (65 vs 36 images, P < 0.001), and longer total fluoroscopy time (81.9 vs 44.4 seconds, P < 0.001). CONCLUSIONS: Patient-level radiation exposure during fluoroscopy-guided hand and wrist procedures is low relative to other common imaging modalities, such as dental radiographs, chest x-rays, and computed tomography scans, and is comparable with less than a few hours of natural background radiation exposure, highlighting the overall safety of this important technology. Further study should be performed to establish reference ranges, which could lead to improved patient counseling and evidence-based guidelines on patient shielding.

The porcine accessory carpal bone as a model for biologic joint replacement for trapeziometacarpal osteoarthritis.

Given its complex shape and relatively small size, the trapezium surface at the trapeziometacarpal (TMC) joint is a particularly attractive target for anatomic biologic joint resurfacing, especially given its propensity to develop osteoarthritis, and the limited and sub-optimal treatment options available. For this to advance to clinical translation, however, an appropriate large animal model is required. In this study, we explored the porcine accessory carpal bone (ACB) as a model for the human trapezium. We characterized ACB anatomy, geometry, joint and tissue-scale mechanics, and composition across multiple donors. We showed that the ACB is similar both in size, and in the saddle shape of the main articulating surface to the human trapezium, and that loads experienced across each joint are similar. Using this information, we then devised a fabrication method and workflow to produce patient-specific tissue-engineered replicas based on CT scans, and showed that when such replicas are implanted orthotopically in an ex vivo model, normal loading is restored. Data from this study establish the porcine ACB as a model system in which to evaluate function of engineered living joint resurfacing strategies. STATEMENT OF SIGNIFICANCE: Biologic joint resurfacing, or the replacement of a joint with living tissue as opposed to metal and plastic, is the holy grail of orthopaedic tissue engineering. However, despite marked advances in engineering native-like osteochondral tissues and in matching patient-specific anatomy, these technologies have not yet reached clinical translation. Given its propensity for developing osteoarthritis, as well as its small size and complex shape, the trapezial surface of the trapeziometacarpal joint at the base of the thumb presents a unique opportunity for pursuing a biologic joint resurfacing strategy. This work establishes the porcine accessory carpal bone as an animal model for the human trapezium and presents a viable test-bed for evaluating the function of engineered living joint resurfacing strategies.

Optimized Media Volumes Enable Homogeneous Growth of Mesenchymal Stem Cell-Based Engineered Cartilage Constructs.

Despite marked advances in the field of cartilage tissue engineering, it remains a challenge to engineer cartilage constructs with homogeneous properties. Moreover, for engineered cartilage to make it to the clinic, this homogeneous growth must occur in a time-efficient manner. In this study we investigated the potential of increased media volume to expedite the homogeneous maturation of mesenchymal stem cell (MSC) laden engineered constructs over time in vitro. We assessed the MSC-laden constructs after 4 and 8 weeks of chondrogenic culture using bulk mechanical, histological, and biochemical measures. These assays were performed on both the intact total constructs and the construct cores to elucidate region-dependent differences. In addition, local strain transfer was assessed to quantify depth-dependent mechanical properties throughout the constructs. Our findings suggest that increased media volume enhances matrix deposition early in culture and ameliorates unwanted regional heterogeneities at later time points. Taken together, these data support the use of higher media volumes during in vitro culture to hasten tissue maturation and increase the core strength of tissue constructs. These findings will forward the field of cartilage tissue engineering and the translation of tissue engineered constructs.

Fabrication and maturation of integrated biphasic anatomic mesenchymal stromal cell-laden composite scaffolds for osteochondral repair and joint resurfacing.

Articular cartilage injury can lead to joint-wide erosion and the early onset of osteoarthritis. To address this, we recently developed a rapid fabrication method to produce patient-specific engineered cartilage tissues to replace an entire articular surface. Here, we extended that work by coupling a mesenchymal stromal cell-laden hydrogel (methacrylated hyaluronic acid) with the porous polycaprolactone (PCL) bone integrating phase and assessed the composition and mechanical performance of these constructs over time. To improve initial construct stability, PCL/hydrogel interface parameters were first optimized by varying PCL pretreatment (with sodium hydroxide before ethanol) before hydrogel infusion. Next, cylindrical osteochondral constructs were formed and cultured in media containing transforming growth factor ß3 for up to 8 weeks, with constructs evaluated for viability, histological features, and biochemical content. Mechanical properties were also assessed in axial compression and via an interface shear strength assay. Results showed that the fabrication process was compatible with cell viability, and that construct biochemical content and mechanical properties increased with time. Interestingly, compressive properties peaked at 5 weeks, while interfacial shear properties continued to improve beyond this time point. Finally, these fabrication methods were combined with a custom mold developed from limb-specific computed tomography imaging data to create an anatomic implantable cell-seeded biologic joint surface, which showedmaturation similar to the osteochondral cylinders. Future work will apply these advances in large animal models of critically sized osteochondral defects to study repair and whole joint resurfacing.

Comparison of Magnetic Resonance Imaging and Ultrasound Evaluations of Zone II Partial Flexor Tendon Lacerations: A Cadaveric Study.

OBJECTIVES: Surgical intervention for zone II high-grade partial flexor tendon lacerations is often required when more than half of the tendon width is torn. Reliable noninvasive tests are critical for optimizing clinical decision making. Our team previously investigated the use of ultrasound (US) for identification of high-grade zone II flexor digitorum profundus lacerations. In this study, we compared magnetic resonance imaging (MRI) to US for the evaluation of high-grade partial flexor tendon lacerations in cadaveric specimens. METHODS: Dissection of 32 digits in 8 fresh-frozen upper extremity cadaveric specimens was performed. The flexor digitorum profundus tendons were randomized into 3 groups: intact, low-grade laceration, and high-grade laceration. A dynamic US examination was performed by a blinded musculoskeletal radiologist. The same specimens underwent hand coil MRI, which was read by the same blinded radiologist. Magnetic resonance imaging test performance metrics were calculated and compared to those computed for the US evaluation. RESULTS: For US evaluation of high-grade lacerations, the sensitivity and specificity were 0.5 and 1.0, with positive likelihood ratio (LR+) and negative likelihood ratio (LR-) values of ∞ and 0.50, respectively. The sensitivity and specificity for MRI evaluation were 0.2 and 1.0, with LR+ and LR- values of ∞ and 0.80. CONCLUSIONS: Both US and MRI are adequate at determining the presence of a high-grade laceration. Magnetic resonance imaging was more specific than US in identification of high-grade partial flexor tendon lacerations. Although less specific, US is a reasonable and less-expensive alternative to MRI when evaluating for clinically significant high-grade partial flexor tendon lacerations.

Four-Year Follow-Up of the World's First Pediatric Bilateral Hand-Forearm Transplants: Do They Grow as Expected?

BACKGROUND: In 2015, the first bilateral pediatric hand-forearm transplant was performed in an 8-year-old boy. The growth rate of the transplanted upper extremities was unknown at the time. METHODS: Forearm and hand radiographs were obtained annually. Radius and ulna measurements were performed by multiple coauthors and mathematically normalized using a standardized methodology. The Greulich and Pyle atlas was used to estimate hand bone age. RESULTS: From July of 2015 to July of 2019, unadjusted bone length (metaphysis to metaphysis) increased 38.8 and 39.6 mm for the left radius and ulna, and 39.5 and 35.8 mm for the right radius and ulna, respectively. Distal physes of the donor limbs increasingly contributed to overall bone length relative to proximal physes. Normalized growth between the two limbs was statistically similar. At each annual follow-up, the bone age increased by 1 year. CONCLUSIONS: Successful pediatric hand-forearm transplantation offers the advantage of growth similar to that of nontransplanted pediatric patients. The transplanted distal physes contributes more to the overall growth, paralleling normal pediatric growth patterns. Chronologic age parallels the increase in bone age. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

A Subperiosteal Proximal Phalanx Osteoid Osteoma: A Challenging Diagnosis.

A relatively rare tumor, osteoid osteoma most commonly affects the lower extremity. In 10% of the cases, it can affect the hand and wrist. We present a case of osteoid osteoma in the proximal phalanx of ring finger that was initially misdiagnosed as a soft tissue lesion. The soft tissue lesion was resected, but the symptoms recurred shortly thereafter, leading to repeat diagnostic workup. Despite X-rays, magnetic resonance imaging, and tissue biopsy, the diagnosis remained elusive until surgical re-exploration. Based on the lessons learned from this case and the experience reported in literature, we discuss the intricate nature of osteoid osteoma diagnosis in the hand, the obstacles often encountered, and how to approach these challenging patients in a stepwise and critical fashion.

The Saline Load Test is Effective at Diagnosing Traumatic Arthrotomies of the Wrist.

BACKGROUND: The saline load test has previously been shown to be an effective tool to diagnose traumatic arthrotomies, but no studies have assessed the test's efficacy in the wrist. The purpose of this study was to investigate the amount of fluid required during a saline load test to detect intra-articular wrist involvement of traumatic wounds with high sensitivity. METHODS: A cadaveric study was conducted using 7 thawed, fresh-frozen forequarter amputations from 7 different donors (3 male, 4 female). Specimen age (mean: 67.7 y, range: 52 to 80 y), laterality (1 right, 6 left), body weight (mean: 164.3 lbs, range: 100 to 223 lbs), and wrist range of motion (ROM) was assessed before testing. The wrist capsule was punctured with an 11-blade scalpel through the 6R radiocarpal portal site under fluoroscopic guidance to ensure the injury was intra-articular. A 19-G needle was then placed through the 3,4 radiocarpal portal site and confirmed with fluoroscopy to ensure intra-articular placement. Normal saline was then injected at a steady rate into the 3,4 radiocarpal portal site until extravasation of the saline was observed from the 6R radiocarpal arthrotomy site. The volume of saline required for extravasation from the 6R radiocarpal arthrotomy was recorded as the volume required to detect the arthrotomy. A plot of saline volumes (by percentile) was created, and a logarithmic distribution was calculated. A Wilcoxon rank-sum test was used to compare injection volumes between male and female specimens, and Pearson Coefficients were used to determine any correlations between injection volume and ROM. RESULTS: The average amount of saline that resulted in extravasation was 4 mL (range: 2 to 7 mL). In order to identify 75%, 90%, 95%, and 99% of the simulated wrist arthrotomies, 5 (95% confidence interval: 3-7), 6 (4-9), 7 (4-10), and 9 (5-14) mL were required, respectively. Pretest ROM did not correlate with saline volume. CONCLUSIONS: This study demonstrates the efficacy of the saline load test in detecting traumatic arthrotomies of the wrist joint with 95% sensitivity after loading 7 mL of saline. Prompt and accurate diagnosis of traumatic arthrotomies is paramount to guide management and optimize postinjury outcomes.

Extracellular vesicles mediate improved functional outcomes in engineered cartilage produced from MSC/chondrocyte cocultures.

Several recent studies have demonstrated that coculture of chondrocytes (CHs) with bone marrow-derived mesenchymal stem cells (MSCs) improves their chondrogenesis. This implies that intercellular communication dictates fate decisions in recipient cells and/or reprograms their metabolic state to support a differentiated function. While this coculture phenomenon is compelling, the differential chondroinductivity of zonal CHs on MSC cocultures, the nature of the molecular cargo, and their transport mechanisms remains undetermined. Here, we demonstrate that juvenile CHs in coculture with adult MSCs promote functional differentiation and improved matrix production. We further demonstrate that close proximity between the two cell types is a prerequisite for this response and that the outcome of this interaction improves viability, chondrogenesis, matrix formation, and homeostasis in the recipient MSCs. Furthermore, we visualized the transfer of intracellular contents from CHs to nearby MSCs and showed that inhibition of extracellular vesicle (EV) transfer blocks the synergistic effect of coculture, identifying EVs as the primary mode of communication in these cocultures. These findings will forward the development of therapeutic agents and more effective delivery systems to promote cartilage repair.

Donor Variation and Optimization of Human Mesenchymal Stem Cell Chondrogenesis in Hyaluronic Acid.

Mesenchymal stem cells (MSCs) are an attractive cell type for cartilage repair that can undergo chondrogenesis in a variety of three-dimensional (3D) scaffolds. Hyaluronic acid (HA) hydrogels provide a biologically relevant interface for cell encapsulation. While previous studies have shown that MSC-laden HA constructs can mature in vitro to match native mechanical properties using cells from animal sources, clinical application will depend on the successful translation of these findings to human cells. Though numerous studies have investigated chondrogenesis of human MSC (hMSC)-laden constructs, their functional outcomes were quite inferior to those using animal sources, and donor-specific responses to 3D HA hydrogels have not been fully investigated. To that end, hMSCs were derived from seven donors, and their ability to undergo chondrogenesis in pellet culture and HA hydrogels was evaluated. Given the initial observation of overt cell aggregation and/or gel contraction for some donors, the impact of variation in cell and HA macromer concentration on functional outcomes during chondrogenesis was evaluated using one young/healthy donor. The findings show marked differences in functional chondrogenesis of hMSCs in 3D HA hydrogels based on donor. Increasing cell density resulted in increased mechanical properties, but also promoted construct contraction. Increasing the macromer density generally stabilized construct dimensions and increased extracellular matrix production, but limited the distribution of formed matrix at the center of the construct and reduced mechanical properties. Collectively, these findings suggest that the use of hMSCs may require tuning of cell density and gel mechanics on a donor-by-donor basis to provide for the most robust tissue formation for clinical application.

Partial Hand Transplant: Lessons Learned From Cadaveric Dissection Studies.

As the field of vascularized composite allotransplantation continues to expand, new upper extremity transplant candidates are being considered. We recently evaluated a bilateral amputee who had a mid-forearm amputation and a contralateral metacarpal hand amputation. In the latter limb, a "partial" hand transplant that preserved the majority of the patient's existing hand, including a partially severed thumb with intact thenar muscle function, was proposed. The feasibility of this partial hand transplant was studied in fresh-frozen cadaver limbs. This report details the proposed approach, the cadaveric dissections, and the lessons learned from these dissections. Issues of osteosynthesis, microvascular planning, and intrinsic muscle recovery are discussed, all of which are critical considerations for partial hand transplant candidates. Ultimately, the partial hand approach was felt to be inferior to a more conventional distal forearm transplant in this particular candidate. Practical, functional, and ethical implications of such decision are presented.

Lesion size measurement in femoral head necrosis.

BACKGROUND: Management of patients with early stages of osteonecrosis of the femoral head remains controversial. Uniform use of an effective method of evaluation and classification, including both stage and lesion size, would allow for comparison and would significantly improve treatment of patients. There is no consensus on how best to determine lesion size. The purpose of this study was to evaluate and compare accuracy and ease of use of different techniques for determining the size of femoral head lesions. METHODS: Twenty-five hips with stages I or II osteonecrosis were evaluated with radiographs and MRI. 3-D MRI measurements of lesion size were used as the standard against which to compare visual estimates and angular measurements: necrotic angle of Kerboul, index of necrosis, and adjusted index of necrosis. RESULTS: 3-D measurements (necrotic volume) showed regular progression from 2.2 to 59.2% of the femoral head. There was a rough correlation with angular measurements; index of necrosis was closer than the necrotic angle. Visual estimates from serial MRI images were as accurate as angular measurements. CONCLUSIONS: Simple visual estimates of lesion size from serial MRI images are reasonably accurate and are satisfactory for clinical use. Angular measurements provide some indication of prognosis and treatment; however, they have limited accuracy, with considerable variability between techniques. 3-D MRI volumetric measurements are the most accurate. Using current techniques and software, they are easier to use, requiring similar time and effort to angular measurements. They should be considered for clinical research and publications when the most accurate measurements are required.

The Impact of Specialty on Cases Performed During Hand Surgery Fellowship Training.

BACKGROUND: Hand surgery fellowship programs in the United States are predominately sponsored by departments or divisions of orthopaedic surgery or plastic surgery. This study compares the operative experiences of hand surgery fellows graduating from orthopaedic or plastic surgery hand surgery fellowships. METHODS: Operative case logs of 3 cohorts of hand surgery fellows graduating during the academic years of 2012-2013, 2013-2014, and 2014-2015 were analyzed. The median case volumes were compared by specialty via Mann-Whitney U tests. An arbitrary 1,000% change between the 90th and 10th percentiles of fellows was used as a threshold to highlight case categories with substantial variability. RESULTS: In this study, 413 orthopaedic hand surgery fellows (87%) and 62 plastic surgery hand surgery fellows (13%) were included. Plastic surgery fellows reported more cases in the following categories: wound closure with graft; wound reconstruction with flap; vascular repair, reconstruction, replantation, or microvascular; closed treatment of fracture or dislocation; nerve injury; and congenital (p < 0.05). Orthopaedic surgery fellows reported more cases in the following categories: wound irrigation and debridement fasciotomy or wound preparation; hand reconstruction or releases; wrist reconstruction, releases, or arthrodesis; forearm, elbow, or shoulder reconstruction or releases; hand fractures, dislocation, or ligament injury; wrist fractures or dislocations; forearm and proximal fractures or dislocations; miscellaneous insertion or removal of devices; shoulder arthroscopy, elbow arthroscopy, and wrist arthroscopy; decompression of tendon sheath, synovectomy, or ganglions; nerve decompression; Dupuytren; and tumor or osteomyelitis (p < 0.05). Plastic surgery fellows reported substantial variability for 12 case categories (range, 1,024% to 2,880%). Orthopaedic surgery fellows reported substantial variability for 9 case categories (range, 1,110% to 9,700%). CONCLUSIONS: Orthopaedic and plastic hand surgery fellowships afford disparate operative experiences. Understanding these differences may help to align prospective trainees with future career goals and to guide discussions to better standardize hand surgery training.

Deferring Routine Wrist Radiography Does Not Affect Management of de Quervain Tendinopathy Patients.

Background Obtaining wrist radiographs prior to surgeon evaluation may be wasteful for patients ultimately diagnosed with de Quervain tendinopathy (DQT). Questions/Purpose Our primary question was whether radiographs directly influence treatment of patients presenting with DQT. A secondary question was whether radiographs influence the frequency of injection and surgical release between cohorts with and without radiographs evaluated within the same practice. Patients and Methods Patients diagnosed with DQT by fellowship-trained hand surgeons at an urban academic medical center were identified retrospectively. Basic demographics and radiographic findings were tabulated. Clinical records were studied to determine whether radiographic findings corroborated history or physical examination findings, and whether management was directly influenced by radiographic findings. Frequencies of treatment with injection and surgery were separately tabulated and compared between cohorts with and without radiographs. Results We included 181 patients (189 wrists), with no differences in demographics between the 58% (110 wrists) with and 42% (79 wrists) without radiographs. Fifty (45%) of imaged wrists demonstrated one or more abnormalities; however, even for the 13 (12%) with corroborating history and physical examination findings, wrist radiography did not directly influence a change in management for any patient in this series. No difference was observed in rates of injection or surgical release either upon initial presentation, or at most recent documented follow-up, between those with and without radiographs. No differences in frequency, types, or total number of additional simultaneous surgical procedures were observed for those treated surgically. Conclusion Wrist radiography does not influence management of patients presenting DQT. Level of Evidence This is a level III, diagnostic study.

Ultrasonographic Evaluation of Zone II Partial Flexor Tendon Lacerations of the Fingers: A Cadaveric Study.

OBJECTIVES: Accurate assessment of zone II partial flexor tendon lacerations in the finger is clinically important. Surgical repair is recommended for lacerations of greater than 50% to 60%. Our goal was to evaluate ultrasonographic test characteristics and accuracy in identifying partial flexor tendon lacerations in a cadaveric model. METHODS: From fresh-frozen above-elbow human cadaveric specimens, 32 flexor digitorum profundus tendons were randomly selected to remain intact or receive low- or high-grade lacerations involving 10% to 40% and 60% to 90% of the radioulnar width within Verdan Zone II, respectively. Static and dynamic ultrasonography using a linear array 14-MHz transducer was performed by a blinded musculoskeletal radiologist. Sensitivities, specificities, and other standard test performance metrics were calculated. Actual and measured percentages of tendon laceration were compared by the paired t test. RESULTS: After randomization, 24 tendons were lacerated (12 low- and 12 high-grade), whereas 8 remained intact. The sensitivity and specificity in detecting the presence versus absence of a partial laceration were 0.54 and 0.75, respectively, with positive and negative likelihood ratio values of 2.17 and 0.61. For low-grade lacerations, the sensitivity and specificity were 0.25 and 0.85, compared to 0.83 and 0.85 for high-grade lacerations. Ultrasonography underestimated the percentage of tendon involvement by a mean of 18.1% for the study population as a whole (95% confidence interval, 9.0% to 27.2%; P < .001) but accurately determined the extent for correctly diagnosed high-grade lacerations (-6.7%; 95% confidence interval, -18.7% to 5.2%; P = .22). CONCLUSIONS: Ultrasonography was useful in identifying and characterizing clinically relevant high-grade zone II partial flexor digitorum profundus lacerations in a cadaveric model.

Role of dexamethasone in the long-term functional maturation of MSC-laden hyaluronic acid hydrogels for cartilage tissue engineering.

The purpose of study was to investigate the maturation of mesenchymal stem cells (MSC) laden in HA constructs with various combinations of chemically defined medium (CM) components and determine the impact of dexamethasone and serum on construct properties. Constructs were cultured in CM with the addition or withdrawal of media components or were transferred to serum containing media that partially represents an in vivo-like condition where pro-inflammatory signals are present. Constructs cultured in CM+ (CM with TGF-ß3) and DEX- (CM+ without dexamethasone) conditions produced robust matrix, while those in ITS/BSA/LA- (CM+ without ITS/BSA/LA) and Serum+ (10% FBS with TGF-ß3) produced little matrix. While construct properties in DEX- were greater than those in CM+ at 4 weeks, properties in CM+ and DEX- reversed by 8 weeks. While construct properties in DEX- were greater than those in CM+ at 4 weeks, the continued absence or removal of dexamethasone resulted in marked GAG loss by 8 weeks. Conversely, the continued presence or new addition of dexamethasone at 4 weeks further improved or maintained construct properties through 8 weeks. Finally, when constructs were converted to Serum (in the continued presence of TGF-ß3 with or without dexamethasone) after pre-culture in CM+ for 4 weeks, GAG loss was attenuated with addition of dexamethasone. Interestingly, however, collagen content and type was not impacted. In conclusion, dexamethasone influences the functional maturation of MSC-laden HA constructs, and may help to maintain properties during long-term culture or with in vivo translation by repressing pro-inflammatory signals. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1717-1727, 2018.

Patient- and Disease-Specific Factors Associated With Operative Management of de Quervain Tendinopathy.

PURPOSE: It remains unclear which factors, patient- or disease-specific, are associated with electing to undergo operative management for de Quervain tendinopathy. Our null hypothesis was that no patient- or disease-specific factors would be associated with the choice of surgical treatment of de Quervain tendinopathy. METHODS: We performed a retrospective review of consecutive patients diagnosed with de Quervain tendinopathy over 3 years by 1 of 3 fellowship-trained hand surgeons at an urban academic institution. Descriptive statistics were calculated for patient baseline and disease-specific characteristics. Cohorts were compared using bivariate analysis for all collected variables. Binary logistic regression with backward stepwise term selection was performed including independent predictors identified by bivariate analysis. RESULTS: A total of 200 patients were identified for inclusion. Bivariate analysis revealed that surgically treated patients were significantly more likely to have Medicaid insurance, psychiatric illness history, and disabled work status. Regression analysis revealed an association between surgical treatment and 2 of the factors evaluated: Medicaid insurance status and psychiatric illness history. CONCLUSIONS: Psychiatric illness and Medicaid insurance status are associated with undergoing surgical release of the first dorsal compartment. These findings support the use of a biopsychosocial framework when treating patients with de Quervain tendinopathy. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Electrospun PLGA Nanofiber Scaffolds Release Ibuprofen Faster and Degrade Slower After In Vivo Implantation.

While delayed delivery of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with improved tendon healing, early delivery has been associated with impaired healing. Therefore, NSAID use is appropriate only if the dose, timing, and mode of delivery relieves pain but does not impede tissue repair. Because delivery parameters can be controlled using drug-eluting nanofibrous scaffolds, our objective was to develop a scaffold for local controlled release of ibuprofen (IBP), and characterize the release profile and degradation both in vitro and in vivo. We found that when incubated in vitro in saline, scaffolds containing IBP had a linear release profile. However, when implanted subcutaneously in vivo or when incubated in vitro in serum, scaffolds showed a rapid burst release. These data demonstrate that scaffold properties are dependent on the environment in which they are placed and the importance of using serum, rather than saline, for initial in vitro evaluation of biofactor release from biodegradable scaffolds.

Enhanced nutrient transport improves the depth-dependent properties of tri-layered engineered cartilage constructs with zonal co-culture of chondrocytes and MSCs.

Biomimetic design in cartilage tissue engineering is a challenge given the complexity of the native tissue. While numerous studies have generated constructs with near-native bulk properties, recapitulating the depth-dependent features of native tissue remains a challenge. Furthermore, limitations in nutrient transport and matrix accumulation in engineered constructs hinders maturation within the central core of large constructs. To overcome these limitations, we fabricated tri-layered constructs that recapitulate the depth-dependent cellular organization and functional properties of native tissue using zonally derived chondrocytes co-cultured with MSCs. We also introduced porous hollow fibers (HFs) and HFs/cotton threads to enhance nutrient transport. Our results showed that tri-layered constructs with depth-dependent organization and properties could be fabricated. The addition of HFs or HFs/threads improved matrix accumulation in the central core region. With HF/threads, the local modulus in the deep region of tri-layered constructs nearly matched that of native tissue, though the properties in the central regions remained lower. These constructs reproduced the zonal organization and depth-dependent properties of native tissue, and demonstrate that a layer-by-layer fabrication scheme holds promise for the biomimetic repair of focal cartilage defects. STATEMENT OF SIGNIFICANCE: Articular cartilage is a highly organized tissue driven by zonal heterogeneity of cells, extracellular matrix proteins and fibril orientations, resulting in depth-dependent mechanical properties. Therefore, the recapitulation of the functional properties of native cartilage in a tissue engineered construct requires such a biomimetic design of the morphological organization, and this has remained a challenge in cartilage tissue engineering. This study demonstrates that a layer-by-layer fabrication scheme, including co-cultures of zone-specific articular CHs and MSCs, can reproduce the depth-dependent characteristics and mechanical properties of native cartilage while minimizing the need for large numbers of chondrocytes. In addition, introduction of a porous hollow fiber (combined with a cotton thread) enhanced nutrient transport and depth-dependent properties of the tri-layered construct. Such a tri-layered construct may provide critical advantages for focal cartilage repair. These constructs hold promise for restoring native tissue structure and function, and may be beneficial in terms of zone-to-zone integration with adjacent host tissue and providing more appropriate strain transfer after implantation.