Multiligament Knee Reconstruction of the ACL, PLC, and ALL in a Floating Knee: A Case Report.

Introduction: Ipsilateral fracture of the femur and tibia, known by the moniker "floating knee," is a serious injury that primarily results from high-energy trauma. Up to 53% of patients with floating knee injuries have concurrent ligamentous injuries, with the anterior cruciate ligament (ACL) as the most commonly affected ligament. Approximately 10% of multi-ligament knee injuries consist of injuries to both the ACL and posterolateral corner (PLC); however, the literature reporting the management of this patient population is sparse, particularly, with a lack of consensus on the timing and protocol of surgical treatment. Well-characterized treatment guidelines are needed for patients with concomitant floating knee and multi-ligament knee injuries. Case Report: A 26-year-old, previously healthy male involved in a high-speed motor vehicle collision presented with upper and lower extremity, skull, and facial fractures, sacropelvic dissociation, and epidural hematoma. Here we describe a rare instance of a floating knee with a multi-ligament knee injury treated through early reconstruction of the ACL, PLC, and anterolateral ligament following stabilization of long bone fractures. Post-injury day 18, the patient underwent single-stage reconstruction of his multi-ligament knee injury. The timing of this was chosen to allow for capsular scar formation to aid in arthroscopy. Conclusion: Our surgical algorithm consists of allograft reconstruction using an all-inside ACL technique and a modified anatomical PLC technique. We recommend early (1-3 weeks) surgical treatment of multi-ligament knee injuries for patients without a closed head injury; however, an individualized treatment approach should be sought, considering the severity of ligamentous injuries, pre-injury activity level, extent of soft-tissue damage, and the activity goals of the patient post-injury. In patients with floating knee injuries, the proposed surgical algorithm here may be utilized for successful multi-ligament knee injury reconstruction.

Glenoid bone augmentation: a contemporary and comprehensive systematic review of open procedures.

Introduction: There is a trend towards arthroscopically treating shoulder instability with glenoid deficiency. Despite this, there remains the option for treatment through an open technique. Multiple bone augmentation options are available for recurrent anterior shoulder instability. Objective: To provide a systematic review of recent studies for recurrent anterior shoulder instability necessitating glenoid bone augmentation specifically through open procedures using coracoid bone or free bone blocks [iliac crest bone autograft/allograft or distal tibia allograft (DTA)]. Methods: PubMed, Cochrane, EMBASE, and Google Scholar were searched for studies reporting open glenoid bone augmentation procedures with iliac crest, tibia, or coracoid bones within 10 years. Extracted data included study/patient characteristics, techniques, prior surgeries, prior dislocations, radiographic findings, range of motion (ROM), recurrent instability, patient-reported outcomes, and complications. Results: 92 met inclusion criteria (5693 total patients). Six were studies of iliac crest bone, four of DTA, and 84 using the coracoid bone. 29 studies measured postoperative arthritis showing no development or mild arthritis. 26 studies reported postoperative graft position. 62 studies reported ROM noting decline in internal/external rotation. 87 studies measured postoperative instability with low rates. Rowe Scores with noted improvement across 31/59 (52.5%) studies were seen. Common post operative complications included infection, hematoma, graft fracture, nerve injury, pain, and screw-related irritation. Conclusion: Despite a trend towards arthroscopic management of recurrent anterior shoulder instability with glenoid deficiency, open procedures continue to provide satisfactory outcomes. Additionally, studies have demonstrated safe and efficacious use of free bone block graft options in the primary and revision setting.

Return to play and performance in the National Basketball Association after undergoing operative or nonoperative treatment for foot fracture.

Background: The incidence of distal lower extremity fractures in National Basketball Association (NBA) athletes continues to increase. There is a paucity of data regarding return-to-play (RTP) rates and performance after sustaining foot fractures in these athletes. The purpose of this study is to quantify RTP rates and performance in NBA players after sustaining a foot fracture. Methods: Sixty-two NBA athletes suffered foot fractures between 2005 and 2021 according to publicly accessible online data. Each athlete was matched to a control player based on age at start of career, age at index injury year, body mass index (BMI), and position played. Performance statistics from 3 seasons prior and 3 seasons following the index injury season were recorded. Results: We found that players who suffered foot fracture injuries are expected to make a full recovery and reach their previous level of performance within three years. 100% of players treated nonoperatively returned to play; meanwhile only 90% of players who were treated operatively returned to play. This difference is statistically significant. Conclusion: NBA athletes have a high RTP rate after sustaining a foot fracture. Players may experience an initial decrease in playing time and performance when returning to play, however, these variables were found to return to baseline over time. After three seasons, player statistics returned to baseline in mostly every category, including player efficiency rating (PER). We found that players are expected to make a full recovery and return to their previous level of performance, regardless of whether they were treated operatively or not. Players treated nonoperatively returned to play at a rate of 100% meanwhile those treated operatively returned at a rate of 90%. Therefore, it is our recommendation that players opt for nonoperative treatment when possible.

Bikini Incision vs Longitudinal Incision for Anterior Total Hip Arthroplasty: A Systematic Review.

Background: Direct anterior approach total hip arthroplasty (DAA THA) traditionally involves a longitudinal incision, but a bikini incision may improve postoperative scar cosmesis and patient satisfaction while reducing wound complications. This systematic review compares the clinical outcomes and surgical complications in patients undergoing DAA THA via a bikini vs longitudinal incision. Methods: A Preferred Reporting Items for Systematic Review and Meta-Analyses-compliant search of PubMed, Cochrane, and EMBASE was performed to identify original articles comparing patients undergoing DAA THA via a bikini vs longitudinal incision published from 2010 to 2021. Patient demographic data and postoperative outcomes (scar appearance, patient satisfaction, functional hip scores, and complications) were collected and qualitatively evaluated. Results: A total of 8 double-armed studies were included, allowing comparison of clinical outcomes of a bikini incision (n = 952) vs a longitudinal incision (n = 1361). Three out of 4 (75.0%) studies comparing postoperative scar appearance and patient satisfaction reported improvements following bikini incision, while 1 study reported comparable results between incision types. Postoperative hip function was similar between incision types in 3 of 4 (75.0%) studies comparing this outcome. Lateral femoral cutaneous nerve injury was the most frequently reported complication following anterior THA, but rates were low overall, and most injuries resolved. Conclusions: Bikini incision appears to be a safe alternative to the traditional longitudinal incision, with similar functional hip outcomes and potentially improved cosmesis and patient satisfaction while reducing wound complications. Current evidence suggests an elevated risk of lateral femoral cutaneous nerve injury with bikini incision, but this needs to be confirmed in further prospective randomized studies.

The efficacy of prophylactic vertebroplasty for preventing proximal junctional complications after spinal fusion: a systematic review.

BACKGROUND CONTEXT: Prophylactic vertebroplasty (VP) is performed at the upper level of instrumentation during spinal fusion to reduce the risk of proximal junctional kyphosis (PJK), proximal junctional fracture (PJFx), and proximal junctional failure (PJF). This study investigated the effect of VP on patient outcomes after spinal fusion. PURPOSE: The aim of this systematic review was to evaluate the effect of prophylactic VP on the incidence of PJK in patients with spinal fusion. STUDY DESIGN/SETTING: Level III, systematic review without meta-analysis. PATIENT SAMPLE: Adult patients undergoing spinal fusion with VP. METHODS: A PRISMA-compliant systematic literature review was conducted using PubMed/MEDLINE, Cochrane, and Embase. Included studies were published in English between January 1, 2001, and May 27, 2021, and reported primary data on adult patients undergoing spinal fusion with VP. Studies were excluded for insufficient surgical details; treatment for vertebral compression fracture; and case series and/or reports with <5 patients. The Newcastle-Ottawa Scale was used to assess risk of bias. The primary outcome of interest was PJK. Other outcomes included PJFx, PJF, and adverse events (eg, cement extravasation). Data were expressed as descriptive statistics. RESULTS: Eight studies with 685 total patients (VP: 293 [42.8%]; No VP: 392 (57.2%)) were included. Five studies were comparative and three were single-arm. PJK incidence was reported in five studies (three comparatives, two single-arm) and ranged from 7.9% to 46.4%; incidence was lower in patients with VP in two of three (66.7%) comparative studies, and equal in one of three (33.3%). PJFx was reported in five studies (four comparatives, one single-arm) and ranged from 0.0% to 39.3%; incidence was lower in the VP group in two of four (50.0%) comparative studies, equal in one of four (25.0%), and higher in one of four (25.0%). PJF was reported in five studies (three comparatives, two single-arm) and ranged from 0.0% to 39.3%; incidence was lower in the VP group in two of three (66.7%) comparative studies and equal in one of three (33.3%). Cement extravasation was reported by four studies and ranged from 0% (0/36) to 48.3% (57/118) in patients with prophylactic VP. CONCLUSIONS: Evidence on whether prophylactic VP decreases the incidence of PJK, PJFx, and PJF after spinal fusion is inconclusive and conflicting. Additionally, the risk of cement extravasation following prophylactic VP could not be evaluated due to insufficient evidence. Further research is needed to determine whether VP has a significant impact on patient outcomes and risks.

Osteoid Osteoma of the Coracoid Process Presenting as Adhesive Capsulitis in a 10-Year-Old Male: A Case Report.

A 10-year-old male presented with symptoms in his right shoulder indicative of adhesive capsulitis. Radiographic films did not demonstrate any osseous abnormalities. Magnetic resonance imaging demonstrated the presence of an eccentric lesion within the coracoid process consistent with an osteoid osteoma. Six months after surgical removal the patient is back to full activities. For the pediatric population, surgeons must always consider diagnoses that could alter a patient's growth or result in long-term disability. In particular, an atypical presentation of musculoskeletal disease in a pediatric patient presenting with a disease that typically is seen in the older population warrants further workup.

Coracoclavicular Ligament Reconstruction Using TightRope for Delayed Grade III Acromioclavicular Joint Injury After Ipsilateral Diaphyseal Clavicle Fracture Fixation: Surgical Technique and Review of Current Literature.

Athletes commonly sustain high-energy direct impact injuries to the shoulder, with acromioclavicular joint (ACJ) injuries accounting for over half. Ipsilateral ACJ injury and diaphyseal clavicle fracture occur nearly 7% of the time. There is limited literature offering treatment suggestions for this unique injury pattern and limited evidence providing guidance to suggest which injury patterns should be treated operatively or nonoperatively. Here, we present successful treatment of a high-level athlete utilizing a Knotless TightRope XP placed through a superior clavicle plate with successful return to full activity at 6 months postoperation. The TightRope technique offers the ability to augment through a preexisting superior clavicular plate in a low-profile manner and promote easy suture tensioning to obtain and maintain reduction of the injured ACJ.

Outcomes following balloon tibioplasty versus conventional osteosynthesis techniques for Schatzker type III tibial plateau fractures: a systematic review.

INTRODUCTION: Schatzker type III fractures of the tibial plateau require elevation of the depressed portions to regain articular congruity. Balloon tibioplasty has been used as an alternative to conventional metal instruments for elevation of the lateral tibial plateau. This study compared functional outcomes following balloon tibioplasty or conventional osteosynthesis techniques in patients with type III fractures of the tibial plateau. MATERIALS AND METHODS: A systematic literature search was performed using PubMed, EMBASE, and Cochrane Library to identify studies published through March 29, 2021, pertaining to balloon tibioplasty or conventional osteosynthesis techniques for type III fractures. Non-human studies, opinion or editorial pieces, systematic reviews, case series (< 5 patients), and articles published in a non-English language were excluded. Primary outcomes were Rasmussen clinical score, range of motion, and Knee Society Score (KSS). A Joanna Briggs Institute (JBI) risk of bias assessment was performed for all studies. RESULTS: A total of 95 studies were identified, with 10 studies (and 132 total patients) meeting inclusion criteria: 1 study focused on balloon tibioplasty, 8 studies reported outcomes following conventional osteosynthesis, and 1 study compared outcomes of the two techniques. Mean follow-up times varied widely, from 4 to 76.3 months. Where reported, balloon tibioplasty resulted in good to excellent functional outcomes as indicated by Rasmussen clinical scores (mean 28.3 in a case series; mean 28.9 in a randomized controlled trial) and range of motion (≥ 140° in both studies) 1-2 years following surgery. KSS was not reported consistently enough for comparison. Studies ranged from low to high risk of bias according to the JBI assessment. CONCLUSIONS: Balloon tibioplasty can lead to excellent functional outcomes in patients with depression fractures of the lateral tibial plateau. More research is needed to directly compare outcomes following treatment with balloon tibioplasty or conventional osteosynthesis techniques.

Acute Femoropopliteal Bypass Graft Occlusion After Knee Manipulation Under Anesthesia: A Case Report and Review of Current Literature.

Bilateral tibiofemoral knee dislocations are a relatively rare injury, and there is a scarcity of literature on its appropriate evaluation and treatment. Even less knee dislocations with concomitant popliteal artery injury have been described. Postoperative graft occlusion accounts for approximately half of the overall complication rate, occurring in up to 18% of the patients undergoing femoropopliteal bypass grafting. Furthermore, anticoagulation and antiplatelet therapy after graft placement is a point of contention. Here, we describe a case of a knee dislocation with associated popliteal artery transection treated initially with successful knee-spanning external fixation and arterial grafting, respectively. At 6 weeks after injury, the patient underwent external fixation removal and closed manipulation of the knee for arthrofibrosis. After manipulation, yet still under anesthesia, distal pulses were acutely diminished and subsequent CTA demonstrated femoropopliteal graft thrombosis. This case demonstrates successful recognition, thrombectomy, and restoration of arterial blood flow, which has since been maintained. Written consent by the patient involved in this case report was obtained.

An Assessment of the Impact of SARS-CoV-2 on a Level 1 Trauma Center Including Subgroup Analysis of Orthopedic Injuries and Mechanism of Injury.

Background and objective There is a paucity of medical literature describing the preparedness of hospital institutions to withstand the population effects of a pandemic. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), has had a global impact on all facets of medicine, which has ultimately affected the medical community in a significant manner. Furthermore, there is a scarcity of research regarding the effects of COVID-19 on trauma and acute care surgery injury and admission rates. We conducted this study to examine the effects of the COVID-19 pandemic on both pediatric and adult trauma admissions, injury types, and mechanisms of injury. Materials and methods Data from the Trauma Registry was extracted for all adult (>15 years) and pediatric (<15 years) patients who consulted trauma surgery, acute care surgery, or orthopedic surgery at our center in the year immediately prior to the pandemic (March 1, 2019-February 29, 2020) and during the COVID-19 pandemic (March 1, 2020-February 28, 2021). Patient demographics, cause of injury, injury type and mechanism, and procedures performed were recorded. Results We documented a 4.2% increase in adult encounters compared to the preceding year. There was a significant difference in the distribution of mechanism of injury of adult patients between the two time periods, with the most changes seen in motor-vehicle auto, gunshot, and other vehicle injuries. However, no significant difference was seen in trauma type or intent (assault, self-inflicted, unintentional). Pediatric encounters increased by 6.4% during the COVID-19 pandemic compared to the pre-COVID-19 period. Overall, there was no detectable association between the distribution of encounters by the mechanism of injury and the time period for pediatric encounters. Conclusion This retrospective review of trauma encounters through both pre-COVID-19 and COVID-19 periods outlines the differences in factors such as demographics, injury mechanisms, and injury types between the two time periods. Overall, we expected a decrease in orthopedic-related trauma admissions during the COVID-19 pandemic; however, there was actually an increase of 4.1% in adult encounters and that of 6.4% in pediatric encounters. Our study lays out possible trends in injury patterns that can be correlated with the COVID-19 pandemic and the lockdown period. This information is useful for the healthcare system in that it demonstrates that resources should not be cut down or removed from surgical specialties. At level I facilities, resources need to be allocated for and continued to be provided to emergency rooms and operative services, including supplies and staffing. These departments need to be well-equipped to handle an increased number of trauma patients.

Does shoulder stability differ with or without subscapularis repair after primary reverse total shoulder arthroplasty? A systematic review.

The use of reverse total shoulder arthroplasty (RTSA) has expanded from its original indication as a rotator cuff arthropathy treatment to include a large variety of pathologies. A frequently reported complication with this surgery is postoperative shoulder instability with reported incidence varying widely from 2.3 to 38%. The etiology for this instability is broad and includes prosthesis design, mechanical impingement, surgical technique, and axillary/deltoid function. A PROSPERO-registered systematic review was performed utilizing PRISMA guidelines using Cochrane, PUBMED, Embase, and Eline. Of the 1442 studies initially identified, 7 studies met all inclusion criteria, all of which were level III or IV evidence. All 7 studies evaluated postoperative instability, but no study reported a statistically significant difference in instability rates between the groups. Dislocations occurred in 5 patients (5/679, 0.7%) with subscapularis repair and 8 patients (8/527, 1.5%) without repair. A nonsignificant difference in the risk of instability for surgeries with repair compared to surgeries without repair was found (overall risk difference: 0.01, random effects 95% confidence interval: -0.00 to 0.02, P = .11). This review suggests no difference in postoperative shoulder instability rates between patients that underwent primary RTSA with or without subsequent repair of the subscapularis tendon. Interestingly, one study comparing implants with a medialized or nonlateralized implant showed a significantly increased rate of dislocation with the medialized group compared to the lateralized group. When these groups were then stratified based on subscapularis repair status, there was no increased risk with a nonrepaired tendon. This study suggests that implant design may have more influence on the stability of RTSA than subscapularis status. However, overall, there does appear to be a trend suggesting improved postoperative clinical outcomes and active range of motion for patients with a subscapularis repair vs. without a repair. Further research is needed to better elucidate the ideal combination of surgical technique and implant design to minimize postoperative glenohumeral joint instability while optimizing postoperative clinical outcomes and range of motion after primary RTSA.

The effect of instrumentation staging on patient outcomes in pyogenic vertebral osteomyelitis: A systematic review.

BACKGROUND: Pyogenic vertebral osteomyelitis is a bacterial infection of the vertebral body that is often treatable with antibiotics, but some cases require additional surgical debridement of the infected tissue. Instrumentation is often utilized for stabilization of the spine as part of the surgical treatment, but controversy remains over the relative risks and benefits of acute instrumentation performed simultaneously with debridement versus delayed instrumentation performed days or weeks after debridement. The purpose of this review was to investigate the relative effects of acute and delayed instrumentation in treatment for pyogenic vertebral osteomyelitis on patient outcomes. METHODS: A PRISMA-compliant systematic literature review was conducted to identify studies published between January 1, 1997 and July 23, 2021. Studies were screened for pre-defined inclusion and exclusion criteria. The primary outcome of interest was reinfection. Other outcomes of interest included neurological status, pain, progression of kyphosis, fusion, hardware failure, length of hospitalization, and mortality at two years. Due to the limited multi-armed studies available that distinguish between patients with acute and delayed instrumentation, inferential statistics were not performed, and data are expressed as descriptive statistics. RESULTS: A total of 9 studies met our inclusion criteria, comprising 299 patients, including 113 (37.8%) with surgical treatment without fixation, 138 (46.2%) with acute instrumentation, and 48 (16.1%) with delayed instrumentation. Reinfection rates were 60.0% (15/25) for surgical treatment without fixation, 28.6% (2/7) for the acute instrumentation, and 14.3% (1/7) for the delayed instrumentation group. Pain was present after surgery in 52.0% (13/25) of the surgical treatment without fixation group, 14.3% (1/7) of the acute instrumentation group, and 0% (0/7) of the delayed instrumentation group. CONCLUSIONS: No major differences in patient outcomes were apparent between acute and delayed instrumentation groups. Further research is needed to determine whether instrumentation staging has a significant impact on patient outcomes.

Tranexamic acid dosing strategies and blood loss reduction in multilevel spine surgery: A systematic review and network meta-analysis: Tranexamic acid for multilevel spine surgery.

BACKGROUND: For adults undergoing complex, multilevel spinal surgery, tranexamic acid (TXA) is an antifibrinolytic agent used to reduce blood loss. The optimal dosing of intravenous TXA remains unclear. This systematic review and meta-analysis compare various dosing regimens of intravenous TXA used in patients undergoing multilevel spine surgery (≥2 levels). METHODS: PubMed, Cochrane, and EMBASE databases were searched for English language studies published January 2001 through May 2021 reporting use of TXA versus placebo for multilevel spine surgery. Primary outcomes of interest were intraoperative blood loss volume (BLV) and total BLV. A separate random effects model was fit for each outcome measure. Effect sizes were calculated as pooled mean differences (Diff) with corresponding 95% confidence intervals (CIs). Random effects network meta-analyses assessed whether the specific TXA dosing regimen influenced BLV. RESULTS: Seven studies with 441 patients were included for meta-analysis. Four different TXA dosing regimens were found: 1) 10 mg/kg + 1 mg/kg/h, 2) 10 mg/kg + 2 mg/kg/h, 3) 15 mg/kg, 4) 15 mg/kg + 1 mg/kg/h. Compared to placebo, patients treated with TXA had reduced intraoperative BLV (Diff = -185.0 ml; 95% CI: -302.1, -67.9) and reduced total BLV (Diff = -439.0 ml; 95% CI: -838.5, -39.6). No significant differences in intraoperative BLV among any of the TXA treatment groups was found. Patients given a TXA dose of 15 mg/kg + 1 mg/kg/h had significantly reduced total BLV in comparison to both placebo (Diff = -823.1 ml; 95% CI: -1249.8, -396.4) and a dose of 15 mg/kg (Diff = -581.2; 95% CI: -1106.8, -55.7). CONCLUSIONS: This study found that intravenous TXA is associated with reduced intraoperative and total BLV, but it remains unclear whether there is an optimal TXA dose. Additional trials directly comparing different TXA regimens and administration routes are needed.

Image-Based Profiling of Patient-Derived Pancreatic Tumor-Stromal Cell Interactions Within a Micropatterned Tumor Model.

Pancreatic cancer is one of the most aggressive cancers with a 5-year patient survival rate of 8.2% and limited availability of therapeutic agents to target metastatic disease. Pancreatic cancer is characterized by a dense stromal cell population with unknown contribution to the progression or suppression of tumor growth. In this study, we describe a microengineered tumor stromal assay of patient-derived pancreatic cancer cells to study the heterotypic interactions of patient pancreatic cancer cells with different types of stromal fibroblasts under basal and drug-treated conditions. The population dynamics of tumor cells in terms of migration and viability were visualized as a functional end point. Coculture with cancer-associated fibroblasts increased the migration of cancer cells when compared to dermal fibroblasts. Finally, we imaged the response of a bromodomain and extraterminal inhibitor on the viability of pancreatic cancer clusters surrounding by stroma in microengineered tumor stromal assay. We visualized a codynamic reduction in both cancer and stromal cells with bromodomain and extraterminal treatment compared to the dimethyl sulfoxide-treated group. This study demonstrates the ability to engineer tumor-stromal assays with patient-derived cells, study the role of diverse types of stromal cells on cancer progression, and precisely visualize a coculture during the screening of therapeutic compounds.

Artificial T Cell Mimetics to Combat Melanoma Tumor Growth.

Despite recent breakthroughs in melanoma treatment with anti-PD-1 immunotherapy, innovative approaches are needed to improve off-target effects. In this study, we report a T cell mimetic microparticle delivery of soluble PD1 aiming at providing a carrier substrate for future combinatorial and targeting efforts. Microparticles of sizes varying from (5 µm to-7 µm) were conjugated with soluble mouse or human PD-1 through nearly irreversible binding between streptavidin and biotin. PD-1 conjugated microparticles (PDMPs) suppressed 3-dimensional tumor growth of human A375 and mouse B16-F10 melanoma cells compared to control microparticles conjugated with the Fc portion of human IgG1 (IgG1MPs). This can be attributed to competitive inhibition by PDMPs on a melanoma cell-intrinsic PD-1/PD-L1 pathway. A single, local administration of mPDMPs in a B16-F10 mouse melanoma model inhibited tumor growth significantly compared to control IgMPs at the same dose. CD45+ immune cells were found to infiltrate tumors treated with mPDMPs as a mechanism for tumor control. These results collectively suggest that PDMPs can target the melanoma cell-intrinsic PD-1/PD-L1 pathway and that these artificial T cell mimetics can be the scaffold for further improvements in anti-tumor immunotherapy.

Therapeutic Delivery Specifications Identified Through Compartmental Analysis of a Mesenchymal Stromal Cell-Immune Reaction.

Despite widespread preclinical success, mesenchymal stromal cell (MSC) therapy has not reached consistent pivotal clinical endpoints in primary indications of autoinflammatory diseases. Numerous studies aim to uncover specific mechanisms of action towards better control of therapy using in vitro immunomodulation assays. However, many of these immunomodulation assays are imperfectly designed to accurately recapitulate microenvironment conditions where MSCs act. To increase our understanding of MSC efficacy, we herein conduct a systems level microenvironment approach to define compartmental features that can influence the delivery of MSCs' immunomodulatory effect in vitro in a more quantitative manner than ever before. Using this approach, we notably uncover an improved MSC quantification method with predictive cross-study applicability and unveil the key importance of system volume, time exposure to MSCs, and cross-communication between MSC and T cell populations to realize full therapeutic effect. The application of these compartmental analysis can improve our understanding of MSC mechanism(s) of action and further lead to administration methods that deliver MSCs within a compartment for predictable potency.

Stromalized microreactor supports murine hematopoietic progenitor enrichment.

There is an emerging need to process, expand, and even genetically engineer hematopoietic stem and progenitor cells (HSPCs) prior to administration for blood reconstitution therapy. A closed-system and automated solution for ex vivo HSC processing can improve adoption and standardize processing techniques. Here, we report a recirculating flow bioreactor where HSCs are stabilized and enriched for short-term processing by indirect fibroblast feeder coculture. Mouse 3 T3 fibroblasts were seeded on the extraluminal membrane surface of a hollow fiber micro-bioreactor and were found to support HSPC cell number compared to unsupported BMCs. CFSE analysis indicates that 3 T3-support was essential for the enhanced intrinsic cell cycling of HSPCs. This enhanced support was specific to the HSPC population with little to no effect seen with the Lineagepositive and Lineagenegative cells. Together, these data suggest that stromal-seeded hollow fiber micro-reactors represent a platform to screening various conditions that support the expansion and bioprocessing of HSPCs ex vivo.