Chondrocyte Response to Fresh Autologous Conditioned Serum Versus Freeze-Dried Allogenic Conditioned Serum.

OBJECTIVE: To investigate the cytokine release profile and histological response of human cartilage after exposure to autologous conditioned serum (ACS) and freeze-dried allogenic conditioned serum (FD-CS). DESIGN: Cartilage explants were collected from 6 patients undergoing total knee arthroplasty. ACS and FD-CS were created from patient serum samples. Cartilage samples were divided into 6 groups: (1) untreated control, (2) ACS, (3) FD-CS, (4) untreated interleukin (IL)-1ß (5 ng/ml), (5) IL-1ß + ACS, and (6) IL-1ß + FD-CS. After 12 days, cartilage samples were analyzed with glycosaminoglycan (GAG) concentration normalized to wet weight while comparing cytokine concentrations, and histological scoring. RESULTS: There was a significant decrease in pathology scoring for ACS (P = 0.0368) and FD-CS (P = 0.0368) in the IL-1ß injury groups compared with the untreated IL-1ß insult group. ACS and FD-CS significantly mitigate the IL-1ß induced increase in basic fibroblast growth factor (bFGF) (P = 0.0009 and P = 0.0002, respectively). FD-CS showed a significant decrease in IL-1ß concentration in the presence of IL-1ß insult compared with the untreated IL-1ß group (P < 0.0001). ACS-treated samples had significantly higher concentration of tumor necrosis factor (TNF)-α independent of IL-1ß when compared with samples not treated with biologics (P = 0.0053). CONCLUSIONS: Explanted osteoarthritic cartilage responds favorably and equivalently to treatment with ACS and FD-CS from a histological perspective. Both ACS and FD-CS were able to mitigate the IL-1ß-induced increases in bFGF and FD-CS lowered IL-1ß concentration while increasing interleukin-1 receptor antagonist (IL-1Ra) concentration. Although the cytokine profile of cartilage tissue explants treated with FD-CS appears to be different than that of ACS, this difference does not seem to affect biologic activity of FD-CS.

Patient-Specific Distal Femoral Guides Optimize Cartilage Topography Matching in Osteochondral Allograft Transplantations.

BACKGROUND: Osteochondral allograft (OCA) transplantation is an important surgical technique for full-thickness chondral defects in the knee. For patients undergoing this procedure, topography matching between the donor and recipient sites is essential to limit premature wear of the OCA. Currently, there is no standardized process of donor and recipient graft matching. PURPOSE: To evaluate a novel topography matching technique for distal femoral condyle OCA transplantation using 3-dimensional (3D) laser scanning to create 3D-printed patient-specific instrumentation in a human cadaveric model. STUDY DESIGN: Descriptive laboratory study. METHODS: Human cadaveric distal femoral condyles (n = 12) underwent 3D laser scanning. An 18-mm circular osteochondral recipient defect was virtually created on the medial femoral condyle (MFC), and the position and orientation of the best topography-matched osteochondral graft from a paired donor lateral femoral condyle (LFC) were determined using an in silico analysis algorithm minimizing articular step-off distances between the edges of the graft and recipient defect. Distances between the entire surface of the OCA graft and the underneath surface of the MFC were evaluated as surface mismatch. Donor (LFC) and recipient (MFC) 3D-printed patient-specific guides were created based on 3D reconstructions of the scanned condyles. Through use of the guides, OCAs were harvested from the LFC and transplanted to the reamed recipient defect site (MFC). The post-OCA recipient condyles were laser scanned. The 360° articular step-off and cartilage topography mismatch were measured. RESULTS: The mean cartilage step-off and graft surface mismatch for the in silico OCA transplant were 0.073 ± 0.029 mm (range, 0.005-0.113 mm) and 0.166 ± 0.039 mm (range, 0.120-0.243 mm), respectively. Comparatively, the cadaveric specimens postimplant had significantly larger step-off differences (0.173 ± 0.085 mm; range, 0.082-0.399 mm; P = .001) but equivalent graft surface topography matching (0.181 ± 0.080 mm; range, 0.087-0.396 mm; P = .678). All 12 OCA transplants had mean circumferential step-off differences less than a clinically significant cutoff of 0.5 mm. CONCLUSION: These findings suggest that the use of 3D-printed patient-specific guides for OCA transplantation has the ability to reliably optimize cartilage topography matching for LFC to MFC transplantation. This study demonstrated substantially lower step-off values compared with previous orthopaedic literature when also evaluating LFC to MFC transplantation. Using this novel technique in a model performing MFC to MFC transplantation has the potential to yield further enhanced results due to improved radii of curvature matching. CLINICAL RELEVANCE: Topography-matched graft implantation for focal chondral defects of the knee in patients improves surface matching and has the potential to improve long-term outcomes. Efficient selection of the allograft also allows improved availability of the limited allograft sources.

Fatty Infiltration, Tear Size, and Retraction Size Are Significant Risk Factors for Retear After Arthroscopic Rotator Cuff Repair: A Systematic Review.

PURPOSE: To assess the consistency and quality of risk factor reporting for rotator cuff repair (RCR) retear and identify risk factors most frequently associated with retear. METHODS: A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Of the initial 3,158 studies, a total of 31 met the following inclusion criteria: (1) clinical studies regarding RCR failure, (2) arthroscopic procedures involving RCR, (3) reporting of clinical outcomes, (4) publication within the past 5 years, and (5) studies investigating preoperative risk factors for retear. After full-text review, 18 risk factors were analyzed. RESULTS: The most consistently significant risk factors were acromiohumeral distance (80%), critical shoulder angle (67%), tear size (63%), anterior-posterior dimension (60%), fatty infiltration (FI) (58%), and retraction size (56%). FI was analyzed using different methods among studies, with 63% finding significant results and 50% of all studies performing ordinal analysis. Tear size was inconsistently analyzed quantitatively or qualitatively, with 58% of studies finding significant results and 63% of all studies performing quantitative analysis. Risk factors consistently found to be nonsignificant included age, sex, diabetes mellitus, symptom duration, hand dominance, repair technique, smoking, and body mass index. CONCLUSIONS: Tear size, FI, and retraction size were found to be significant risk factors in most of the included studies evaluating rotator cuff retear. Risk factors less likely reported as predictive included repair technique, age, sex, diabetes mellitus, symptom duration, hand dominance, repair technique, smoking, and body mass index. Risk factors that require further investigation include critical shoulder angle, acromiohumeral distance, and anterior-posterior tear dimension. LEVEL OF EVIDENCE: Level III, systematic review of Level III-IV studies.

Biomechanical Properties and Kinematics of Medial Patellofemoral Ligament Reconstruction: A Systematic Review.

Background: While the biomechanical properties of the native medial patellofemoral ligament (MPFL) have been well studied, there is no comprehensive summary of the biomechanics of MPFL reconstruction (MPFLR). An accurate understanding of the kinematic properties and functional behavior of current techniques used in MPFLR is imperative to restoring native biomechanics and improving outcomes. Purpose: To provide a comprehensive review of the biomechanical effects of variations in MPFLR, specifically to determine the effect of graft choice and reconstruction technique. Study Design: Systematic review. Methods: A systematic review was performed in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A total of 32 studies met inclusion criteria: (1) using ≥8 human cadaveric specimens, (2) reporting on a component of MPFLR, and (3) having multiple comparison groups. Results: Gracilis, semitendinosus, and quadriceps grafts demonstrated an ultimate load to failure (N) of 206.2, 102.8, and 190.0 to 205.0 and stiffness (N/mm) of 20.4, 8.5, and 21.4 to 33.6, respectively. Single-bundle and double-bundle techniques produced an ultimate load to failure (N) of 171 and 213 and stiffness (N/mm) of 13.9 and 17.1, respectively. Anchors placed centrally and superomedially in the patella produced the smallest degree of length changes throughout range of motion in contrast to anchors placed more proximally. Sutures, suture anchors, and transosseous tunnels all produced similar ultimate load to failure, stiffness, and elongation data. Femoral tunnel malpositioning resulted in significant increases in contact pressures, patellar translation, tilt, and graft tightening or loosening. Low tension grafts (2 N) most closely restored the patellofemoral contact pressures, translation, and tilt. Graft fixation angles variably and inconsistently altered contact pressures, and patellar translation and tilt. Conclusion: Data demonstrated that placement of the MPFLR femoral tunnel at the Schöttle point is critical to success. Femoral tunnel diameter should be ≥2 mm greater than graft diameter to limit graft advancement and overtensioning. Graft fixation, regardless of graft choice or fixation angle, is optimally performed under minimal tension with patellar fixation at the medial and superomedial patella. However, lower fixation angles may reduce graft strain, and higher fixation angles may exacerbate anisometry and length changes if femoral tunnel placement is nonanatomic.

A Systematic Review and Meta-analysis of Risk Factors for the Increased Incidence of Revision Surgery After Arthroscopic Rotator Cuff Repair.

BACKGROUND: Approximately 90% of patients who undergo arthroscopic rotator cuff repair (RCR) are satisfied with their pain levels and function after surgery. However, a subset of patients experience continued symptoms that warrant revision surgery. Preoperative risk factors for RCR failure requiring revision surgery have not been clearly defined. PURPOSE: To (1) determine the rate of RCR failure requiring revision surgery and (2) identify risk factors for revision surgery, which will help surgeons to determine patients who are at the greatest risk for RCR failure. STUDY DESIGN: Systematic review and meta-analysis; Level of evidence, 4. METHODS: A systematic review and meta-analysis in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were performed. The initial search resulted in 3158 titles, and 533 full-text articles were assessed for eligibility. A total of 10 studies met the following inclusion criteria: (1) human clinical studies, (2) arthroscopic RCR, (3) original clinical research, and (4) evaluation of preoperative risk factors for revision. RESULTS: After a full-text review, a total of 16 risk factors were recorded and analyzed across 10 studies. Corticosteroid injection was the most consistent risk factor for revision surgery, reaching statistical significance in 4 of 4 studies, followed by workers' compensation status (2/3 studies). Patients with corticosteroid injections had a pooled increased risk of revision surgery by 47% (odds ratio, 1.44 [95% CI, 1.36-1.52]). Patients with workers' compensation had a pooled increased risk of revision surgery by 133% (odds ratio, 2.33 [95% CI, 2.09-2.60]). Age, smoking status, diabetes, and obesity were found to be risk factors in half of the analyzed studies. CONCLUSION: Corticosteroid injections, regardless of the frequency of injections, and workers' compensation status were found to be significant risk factors across the literature based on qualitative analysis and pooled analysis. Surgeons should determine ideal candidates for arthroscopic RCR by accounting for corticosteroid injection history, regardless of the frequency, and insurance status of the patient.

Concomitant Treatment of High-Grade Cartilage Lesions Mitigates Risk of Meniscal Allograft Transplant Failure.

PURPOSE: To identify frequently studied significant preoperative risk factors for meniscal allograft transplantation (MAT) failure. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were used to conduct this systematic review. The database analysis was performed in May of 2022 and included PubMed, Embrace, and Cochrane. Studies between January 1, 2000, and January 1, 2021, were reviewed with search terms, including "meniscal," "meniscus," "transplantation," "transplant," and "allograft." Twenty-one full-text manuscripts met inclusion criteria of studies assessing preoperative risk factors for MAT failure defined as either clinical failure (Lysholm <65) or surgical failure (revision, removal, or conversion to knee arthroplasty). RESULTS: In total, 21 studies were included, comprising 47.6% with a Level of Evidence of Level III and 52.4% with Level of Evidence IV. The analysis involved 2,533 patients, and the mean final follow-up ranged from 2.2 to 20.0 years. The presence of high-grade cartilage defects was the only factor found predictive of MAT surgical failure in the majority of studies in which it was analyzed (5/7 studies, 71.4%). Four of the five studies that found high-grade cartilage defects to be a predictor of MAT surgical failure did not treat all cartilage lesions, while the 2 studies that found high-grade cartilage defects an insignificant predictor of MAT surgical failure treated all defects at the time of MAT. For clinical failure, no risk factors were predictive of MAT failure in the majority of studies, although smoking and concomitant ligamentous or realignment procedures were significant in 1 study. CONCLUSION: The presence of untreated high-grade cartilage appears to elevate the risk of surgical MAT failure; however, concomitant treatment of defects may mitigate their detrimental effect. There is no clear risk factor that consistently predicts clinical failure. Age, sex, BMI, knee compartment, time from prior meniscectomy, femorotibial alignment (after correction), concomitant cartilage procedure, and laterality do not routinely impact MAT failure. LEVEL OF EVIDENCE: Level IV, systematic review.

Indications and Technique: Rotator Cuff Repair Augmentation.

Rotator cuff repair (RCR) augmentation is often considered for patients with large-to-massive rotator cuff tears or chronic tears with poor tissue quality. Augmentation can provide mechanical stability and improved biology to improve the likelihood of a successful repair. This article discusses the indications, diagnosis, surgical techniques, and outcomes for RCR augmentation using an acellular dermal allograft, partially demineralized cancellous allograft, dermal xenograft, bone marrow aspirate concentrate, and platelet-rich plasma.

Biomechanical Analysis of Anteroinferior Bankart Repair Anchor Types.

BACKGROUND: All-suture anchors and knotless anchors are increasingly used in the repair of anteroinferior labral tears in patients with shoulder instability. Optimal repair constructs may limit recurrent instability. PURPOSE: To perform a quantitative biomechanical comparison of 3 labral fixation devices for soft tissue Bankart lesions: knotless soft-body tensionable anchor (SB knotless), knotted soft-body anchor (SB knotted), and knotless hard-body PEEK (polyether ether ketone) interference anchor (HB knotless). STUDY DESIGN: Controlled laboratory study. METHODS: A total of 21 glenoid specimens were randomized into 3 groups: SB knotless, SB knotted, and HB knotless. Artificial Bankart lesions were created at the anteroinferior labrum. Anchors were placed at the 3:30, 4:30, and 5:30 clockface positions, and sutures were passed through 1 cm of tissue. Anchors were tested simultaneously as one construct by pulling capsular tissue connected to the anteroinferior quadrant. Cyclic loading (5-25 N, 100 cycles) was followed by load-to-failure testing (15 mm/min). Biomechanical testing variables were collected, and failure mechanisms were recorded per individual anchor. RESULTS: There were no differences in baseline specimen characteristics. There was no difference in elongation during cyclic loading (P = .40). The ultimate load to failure between SB knotless (309.7 ± 125.6 N), SB knotted (226.4 ± 34.8 N), and HB knotless (256.5 ± 90.5 N) did not significantly differ (P = .25). Failure mechanisms differed among groups (P = .008); mechanisms included anchor pullout (SB knotless: 33.3%; SB knotted: 23.8%; HB knotless: 28.6%), suture pull-through (SB knotless: 66.7%; SB knotted: 38.1%; HB knotless: 33.3%), and anchor fixation method failure, defined as knot failure for knotted anchors or locking mechanism failure for knotless anchors (SB knotless: 0.0%; SB knotted: 38.1%; HB knotless: 38.1%).). CONCLUSION: The SB knotless, SB knotted, and HB knotless labral fixation anchors studied exhibited comparable elongation during cyclic loading, stiffness, and ultimate loads to failure in a cadaveric model. However, the failure mechanisms significantly differed, as SB knotless anchors failed primarily from suture pull-through, while SB knotted and HB knotless anchors were subject to knot failure and locking mechanism failure, respectively. CLINICAL RELEVANCE: These data support the benefit of SB knotless anchors for anteroinferior labral repair in limiting knot failure typically seen with knotted anchors, perhaps demonstrating that all-suture anchors may have better locking mechanism quality than their PEEK counterparts.

Artificial intelligence-based HDX (AI-HDX) prediction reveals fundamental characteristics to protein dynamics: Mechanisms on SARS-CoV-2 immune escape.

Three-dimensional structure and dynamics are essential for protein function. Advancements in hydrogen-deuterium exchange (HDX) techniques enable probing protein dynamic information in physiologically relevant conditions. HDX-coupled mass spectrometry (HDX-MS) has been broadly applied in pharmaceutical industries. However, it is challenging to obtain dynamics information at the single amino acid resolution and time consuming to perform the experiments and process the data. Here, we demonstrate the first deep learning model, artificial intelligence-based HDX (AI-HDX), that predicts intrinsic protein dynamics based on the protein sequence. It uncovers the protein structural dynamics by combining deep learning, experimental HDX, sequence alignment, and protein structure prediction. AI-HDX can be broadly applied to drug discovery, protein engineering, and biomedical studies. As a demonstration, we elucidated receptor-binding domain structural dynamics as a potential mechanism of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody efficacy and immune escape. AI-HDX fundamentally differs from the current AI tools for protein analysis and may transform protein design for various applications.

Biphasic Interpositional Allograft for Rotator Cuff Repair Augmentation Is Safe in an Ovine Model.

PURPOSE: To perform a preclinical histologic assessment of a biphasic acellular interpositional cancellous allograft in an ovine model of rotator cuff repair (RCR) designed to better understand its safety profile and effects on tendon healing after RCR. METHODS: Thirty skeletally mature sheep with clinically normal shoulders with an artificially created degenerative infraspinatus tendon tear were randomized to control and treatment groups. Animals were euthanized at 3 weeks, 6 weeks, and 12 weeks. After gross dissection, rotator cuff specimens were fixed with formalin and polymerized for sectioning and staining. Blinded histologic scores evaluated inflammatory cell infiltrates, signs of degradation, particulate debris, collagen arrangement, neovascularization, and enthesis qualitative measures. RESULTS: There were no treatment specimens that exhibited histologic signs of a significant infection, inflammatory infiltrate, or foreign body reaction such as granuloma or fibrous capsule formation. Histologic scores in all categories were not significantly different at all time points, including the primary end point mean cumulative inflammatory score (control: 3.66 ± 1.21 vs treated: 4.33 ± 1.51, P = .42), when comparing the treatment and control RCR groups. In general, the degree of tendon healing and host tissue response was essentially equivalent between the 2 groups with observation of low overall levels of inflammation and progressive improvements in collagen organization, reduced tenocyte activity, and fibrocartilaginous enthesis reformation. CONCLUSIONS: This histologic study demonstrated the use of a biphasic interpositional allograft for RCR augmentation in an ovine model does not generate an inflammatory response or foreign body reaction. Use of the biphasic interpositional allograft resulted in a histological profile that was essentially equivalent to that of a standard RCR at 3-, 6-, and 12-week postoperative timepoints. These findings suggest that a biphasic interpositional allograft is safe for further clinical investigation in humans before broader clinical application. CLINICAL RELEVANCE: Patch augmentation of RCR is a popular technique that has shown clinical success in improving the likelihood of a successful repair in patients at elevated risk for retear. Newer augmentation technologies are being developed to address the biology at the interface between the bone and soft tissue where failure typically occurs.

Factors That Affect the Magnitude of Tibial Tubercle-Trochlear Groove Distance in Patients With Patellar Instability.

BACKGROUND: Tibial tubercle-trochlear groove (TT-TG) distance is a risk factor for recurrent patellar dislocation and is often included in algorithmic treatment of instability. The underlying factors that determine TT-TG have yet to be clearly described in orthopaedic literature. PURPOSE/HYPOTHESIS: The purpose of our study was to determine the underlying anatomic factors contributing to TT-TG distance. We hypothesized that degree of tubercle lateralization and knee rotation angle may substantially predict TT-TG. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: All patients evaluated for patellar instability at a single institution between 2013 and 2021 were included. Patients with previous knee osseous procedures were excluded. TT-TG and its anatomic relationship to patellofemoral measures, including dysplasia, femoral anteversion, tibial tubercle lateralization, knee rotation angle, and tibial torsion, were measured and subsequently quantified using univariate and multivariable analysis. RESULTS: In total, 76 patients met the inclusion criteria (46 female, 30 male; mean ± SD age, 20.6 ± 8.6 years) and were evaluated. Mean TT-TG was 16.2 ± 5.4 mm. On univariate analysis, increasing knee rotation angle (P < .01), tibial tubercle lateralization (P = .02), and tibial torsion (P = .01) were associated with increased TT-TG. In dysplastic cases, patients without medial hypoplasia (Dejour A or B) demonstrated significantly increased TT-TG (18.1 ± 5.4 mm) as compared with those with medial hypoplasia (Dejour C or D; TT-TG: 14.9 ± 5.2 mm; P = .02). Multivariable analysis revealed that increased knee rotation angle (+0.43-mm TT-TG per degree; P < .01) and tubercle lateralization (+0.19-mm TT-TG per percentage lateralization; P < .01) were statistically significant determinants of increased TT-TG distance. Upon accounting for these factors, tibial torsion, trochlear width, and medial hypoplasia were no longer significant components in predicting TT-TG (P≥ .54). Of note, all patients with TT-TG ≥20 mm had tibial tubercle lateralization ≥68%, a knee rotation angle ≥5.8°, or both factors concurrently. CONCLUSION: TT-TG distance is most influenced by knee rotation angle and tibial tubercle lateralization.