No Correlation Exists Between Tibial- and Femoral-Based Measurements of Patella Alta in a Population With Chronic Patellofemoral Pain or Instability Undergoing Patella Distalization.

PURPOSE: To investigate whether the patellotrochlear index (PTI) predicts patella alta as determined by tibial-based methods of Insall-Salvati (IS) and Caton-Deschamp (CDI) indexes in a pathological population (with patellofemoral pain and/or instability), in addition to determining whether PTI and sagittal patellofemoral engagement (SPE) correlate with trochlea length as determined by lateral condyle index (LCI). METHODS: Patients with confirmed patella alta (IS/CDI ratio >1.2) undergoing tibial tubercle osteotomy for patellofemoral pain/instability with an available magnetic resonance imaging (MRI) scans were included. Patients who had undergone previous soft-tissue realignment, previous surgery, or trauma to the extensor mechanism were excluded. Two raters measured the IS, CDI, PTI, SPE, LCI, and knee flexion angle (KFA) on MRI. Interobserver reliability and correlation between measurements were calculated. RESULTS: In total, 71 knees were included. PTI (0.73), SPE (0.836), LCI (0.701), and KFA (0.8) demonstrated good- to near-excellent interobserver reliability. IS (0.65) and CDI (0.66) demonstrated moderate interobserver reliability. PTI and SPE showed the strongest significant correlation (0.8112, P = 2.2 × 10-16). IS and CD (0.39, P = .0007) showed a moderate significant correlation. PTI and KFA (0.53, P = 1.685 × 10-6) and SPE and KFA (0.61, P = 1.991 × 10-8) had a significant moderate correlation. LCI and KFA (-0.37, P = .0017) showed a significant moderate negative correlation. All other measurement indices correlated poorly and were insignificant. A total of 94.4% of the knees were defined as having patella alta using IS, with the remaining 5.6% having a raised CDI. Only 14% of cases had an IS of >1.2, a CDI >1.2, and a PTI <0.125, which increased to 39% (28/71) when the threshold for PTI was increased to <0.28. CONCLUSIONS: There was no correlation between tibial (IS and CD) and femoral methods (PTI and SPE) of quantifying patella alta. PTI and SPE did not correlate with trochlea length as measured by LCI. PTI, SPE, and LCI are significantly affected by the KFA during MRI. LEVEL OF EVIDENCE: Level IV, retrospective diagnostic radiographic investigation.

Midterm outcome of superior capsular reconstruction using doubled acellular human dermal allograft for irreparable rotator cuff tear.

BACKGROUND: Thicker (folded) facia lata autografts have been shown to be superior to thinner grafts and single-layered acellular human dermal (HD) allografts for superior capsular reconstruction (SCR) in biomechanical studies. The aim of this study was to evaluate the midterm clinical outcomes following SCR for irreparable supraspinatus tears using doubled (folded) HD allograft. METHODS: Thirty-two patients who had undergone SCR using doubled HD allograft between February 2012 and January 2020 were recruited in a continuous manner in this retrospective study. The inclusion criteria were SCR performed for irreparable supraspinatus tear and a minimum of 2 years' follow-up. The primary outcome measure was the American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) score. The secondary outcome measures were complications and revision surgery. A subgroup analysis was performed between patients who received a "standard" graft of mean 3-mm thickness or a "thick" graft of mean 4.4-mm thickness. RESULTS: One patient was lost to follow-up. A total of 31 patients (31 shoulder joints) were analyzed with a mean follow-up duration of 48 months (range, 25-96 months). Following surgery, there was significant improvement in the ASES score from 18.1 ± 14.3 (preoperative) to 76.3 ± 25.1 (postoperative) (P < .001), with a satisfactory clinical outcome obtained in 83.8% of the patients. In a subset of 8 patients completing 5 years' follow-up, the clinical improvements were sustained. The percentage of patients with a clinically successful outcome was higher among those with thick grafts compared to those with standard grafts, although this failed to reach statistical significance (94.4% vs. 69.2%, risk ratio 1.36, 95% confidence interval 0.93-1.99, P = .13). One patient within the standard group underwent revision surgery. CONCLUSION: SCR for irreparable rotator cuff tears with doubled HD allograft results in improved clinical outcomes and low reoperation at midterm follow-up duration.

Injectable hydrogels: An emerging therapeutic strategy for cartilage regeneration.

The impairment of articular cartilage due to traumatic incidents or osteoarthritis has posed significant challenges for healthcare practitioners, researchers, and individuals suffering from these conditions. Due to the absence of an approved treatment strategy for the complete restoration of cartilage defects to their native state, the tissue condition often deteriorates over time, leading to osteoarthritic (OA). However, recent advancements in the field of regenerative medicine have unveiled promising prospects through the utilization of injectable hydrogels. This versatile class of biomaterials, characterized by their ability to emulate the characteristics of native articular cartilage, offers the distinct advantage of minimally invasive administration directly to the site of damage. These hydrogels can also serve as ideal delivery vehicles for a diverse range of bioactive agents, including growth factors, anti-inflammatory drugs, steroids, and cells. The controlled release of such biologically active molecules from hydrogel scaffolds can accelerate cartilage healing, stimulate chondrogenesis, and modulate the inflammatory microenvironment to halt osteoarthritic progression. The present review aims to describe the methods used to design injectable hydrogels, expound upon their applications as delivery vehicles of biologically active molecules, and provide an update on recent advances in leveraging these delivery systems to foster articular cartilage regeneration.

A pilot randomised controlled trial assessing standard versus dermal patch-augmented rotator cuff repair found no adverse effects and suggest future trials need a minimum of 150 patients.

PURPOSE: The aims of this pilot randomised controlled trial (RCT) were to assess the safety and efficacy of a human dermal allograft patch and assess the feasibility of a future RCT comparing retear rate and functional outcome 12 months following standard and augmented double-row rotator cuff repair. METHODS:  A pilot RCT was conducted among patients undergoing arthroscopic repair of rotator cuff tear measuring between 1 and 5 cm. They were randomised to either augmented (double-row repair with human acellular dermal patch) or standard (double-row repair only). The primary outcome was rotator cuff retear determined on MRI scan at 12 months using the Sugaya's classification (grade 4 or 5). All adverse events were recorded. Functional assessment was performed at baseline and 3, 6, 9, and 12 months post-surgery using clinical outcome scores. Safety was assessed by complications and adverse effects, and feasibility by recruitment, follow-up rate and proof of concept statistical analyses of a future trial. RESULTS: Between 2017 and 2019, 63 patients were considered for inclusion. Twenty-three patients were excluded, leaving 40 patients (20 per group) in the final study population. The mean tear sizes were 3.0 cm in the augmented and 2.4 cm in the standard group. There was one adhesive capsulitis in the augmented group, with no other adverse events. Retear was observed in 4/18 (22%) of patients in the augmented and 5/18 (28%) in the standard group. In both groups, functional outcome improved significantly which was clinically meaningful for all scores, with no difference between groups. Retear rate increased with tear size. Future trials are feasible but need a minimum total sample size of 150 patients. CONCLUSION:  Clinically meaningful improved function without adverse effects was found with human acellular dermal patch-augmented cuff repairs. LEVEL OF EVIDENCE: Level II.

Cost-effectiveness of a new ACI technique for the treatment of articular cartilage defects of the knee compared to regularly used ACI technique and microfracture.

AIMS: For patients with cartilage defects of the knee, a new biocompatible and in situ cross-linkable albumin-hyaluronan-based hydrogel has been developed for matrix-associated autologous chondrocyte implantation (M-ACI) - NOVOCART Inject plus (Ninject; TETEC AG, Reutlingen, Germany). We aimed to estimate the potential cost-effectiveness of NInject, that is not available on the market, yet compared to spheroids of human autologous matrix-associated chondrocytes (Spherox; CO.DON GmbH, Leipzig, Germany) and microfracture. MATERIALS AND METHODS: An early Markov model was developed to estimate the cost-effectiveness in the United Kingdom (UK) from the payer perspective. Transition probabilities, response rates, utility values and costs were derived from literature. Since NInject has not yet been launched and no prices are available, its costs were assumed equal to those of Spherox. Cycle length was set at one year and the time horizon chosen was notional patients' remaining lifetime. Model robustness was evaluated with deterministic and probabilistic sensitivity analyses (DSA; PSA) and value of information analysis (VOIA). The Markov model was built using TreeAge Pro Healthcare. RESULTS: NInject was cost-effective compared to microfracture (ICER: £5,147) while Spherox was extendedly dominated. In sensitivity analyses, the ICER exceeded conventional WTP threshold of £20,000 only when the utility value after successful first treatment with NInject was decreased by 20% (ICER: £69,620). PSA corroborated the cost-effectiveness findings of NInject, compared to both alternatives, with probabilities of 60% of NInject undercutting the aforementioned WTP threshold and being the most cost-effective alternative. The VOIA revealed that obtaining additional evidence on the new technology will likely not be cost-effective for the UK National Health Service. LIMITATIONS AND CONCLUSION: This early Markov model showed that NInject is cost-effective for the treatment of articular cartilage defects in the knee, compared to Spherox and microfracture. However, as the final price of NInject has yet to be determined, the cost-effectiveness analysis performed in this study is provisional, assuming equal prices for NInject and Spherox.

A Randomized Trial of Autologous Chondrocyte Implantation Versus Alternative Forms of Surgical Cartilage Management in Patients With a Failed Primary Treatment for Chondral or Osteochondral Defects in the Knee.

BACKGROUND: There are limited randomized controlled trials with long-term outcomes comparing autologous chondrocyte implantation (ACI) versus alternative forms of surgical cartilage management within the knee. PURPOSE: To determine at 5 years after surgery whether ACI was superior to alternative forms of cartilage management in patients after a failed previous treatment for chondral or osteochondral defects in the knee. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: In total, 390 participants were randomly assigned to receive either ACI or alternative management. Patients aged 18 to 55 years with one or two symptomatic cartilage defects who had failed 1 previous therapeutic surgical procedure in excess of 6 months prior were included. Dual primary outcome measures were used: (1) patient-completed Lysholm knee score and (2) time from surgery to cessation of treatment benefit. Secondary outcome measures included International Knee Documentation Committee and Cincinnati Knee Rating System scores, as well as number of serious adverse events. Analysis was performed on an intention-to-treat basis. RESULTS: Lysholm scores were improved by 1 year in both groups (15.4 points [95% CI, 11.9 to 18.8] and 15.2 points [95% CI, 11.6 to 18.9]) for ACI and alternative, with this improvement sustained over the duration of the trial. However, no evidence of a difference was found between the groups at 5 years (2.9 points; 95% CI, -1.8 to 7.5; P = .46). Approximately half of the participants (55%; 95% CI, 47% to 64% with ACI) were still experiencing benefit at 5 years, with time to cessation of treatment benefit similar in both groups (hazard ratio, 0.97; 95% CI, 0.72 to 1.32; P > .99). There was a differential effect on Lysholm scores in patients without previous marrow stimulation compared with those with marrow stimulation (P = .03; 6.4 points in favor of ACI; 95% CI, -0.4 to 13.1). More participants experienced a serious adverse event with ACI (P = .02). CONCLUSION: Over 5 years, there was no evidence of a difference in Lysholm scores between ACI and alternative management in patients who had previously failed treatment. Previous marrow stimulation had a detrimental effect on the outcome of ACI. REGISTRATION: International Standard Randomised Controlled Trial Number: 48911177.

Cost-Effectiveness Analysis of a Medial Meniscus Replacement Prosthesis for the Treatment of Patients with Medial Compartment Pain in the United Kingdom.

BACKGROUND: The most common intra-articular knee injury is a meniscal tear, which commonly occurs secondary to trauma following twisting or hyperflexion. Treatment options for meniscal tears can either be surgical or non-surgical, and range from rest, exercise, bracing and physical therapy to surgical intervention, including meniscal repair and partial meniscectomy. In patients with persistent pain following loss of meniscus tissue, treatment can include partial replacement or meniscal allograft transplantation. The NUsurface® prosthesis has been developed as a treatment option for patients experiencing persistent knee pain post medial meniscus (MM) surgery. OBJECTIVE: The aim of this study was to assess the cost effectiveness of MM replacement using NUsurface for the treatment of patients with medial compartment pain following previous partial medial meniscectomy, from a UK health service perspective. METHODS: An economic decision-analytic model was developed to assess the cost per quality-adjusted life-year (QALY) gained associated with the introduction of MM replacement using NUsurface compared with non-surgical standard of care, over a lifetime time horizon. The model structure was primarily informed by a previous clinical trial (VENUS) and was developed based on the clinical pathways typically followed by patients with this condition, with treatment pathways and probabilities of clinical progression adjusted depending on whether patients were receiving the intervention or undergoing current practice. A hypothetical cohort of adult patients (mean age of 50 years) was modelled, with clinical data sourced from the VENUS study as well as relevant UK literature. Both deterministic and probabilistic sensitivity analyses were carried out to explore uncertainty in the model results. RESULTS: The base-case probabilistic results indicate that MM replacement using NUsurface is likely to be cost effective across a range of willingness-to-pay (WTP) thresholds (95% probability of being cost effective at the National Institute for Health and Care Excellence (NICE)-recommended £20,000 WTP threshold). Although per-patient costs increase, QALYs are also gained, with the incremental cost per QALY (probabilistic value = £5011) being below £20,000. Deterministic sensitivity analyses indicate that the parameters that have the greatest impact on results are the failure rate in the control group (current practice), utility scores, and the cost of undergoing MM replacement using NUsurface. CONCLUSIONS: Based on the analysis presented, MM replacement with the NUsurface prosthetic implant is likely to be a cost-effective use of UK health care service resources compared with current standard care.

A 2021 consensus statement on osteotomies around the knee by the UK Knee Osteotomy consensus Group (KOG).

BACKGROUND: There are significant deficiencies in the evidence base of modern-day osteotomy which result in significant variation in practice between surgeons. The purpose of this statement was to develop a consensus statement on the practice of osteotomy so that a more standardized approach to the indications, surgical technique, and postoperative care could be outlined. The article is also intended to educate and inform the practice of individuals who are early in their experience and/or clinical practice. METHOD: A group of 29 specialist knee surgeons who regularly perform osteotomy was convened to form the Knee Osteotomy consensus Group (KOG). Consensus was determined utilizing the consensus group technique described by List. A total of 37 questions were asked covering all aspects of clinical practice. RESULTS: 20 statements were generated and debated until a criterion level of 70% was met. CONCLUSIONS: Consensus was achieved regarding 20 statements concerning Indications for surgery, decision making, surgical planning, technique, post-operative assessment and recovery.

Cell therapy for cartilage repair.

Regenerative medicine, using cells as therapeutic agents for the repair or regeneration of tissues and organs, offers great hope for the future of medicine. Cell therapy for treating defects in articular cartilage has been an exemplar of translating this technology to the clinic, but it is not without its challenges. These include applying regulations, which were designed for pharmaceutical agents, to living cells. In addition, using autologous cells as the therapeutic agent brings additional costs and logistical challenges compared with using allogeneic cells. The main cell types used in treating chondral or osteochondral defects in joints to date are chondrocytes and mesenchymal stromal cells derived from various sources such as bone marrow, adipose tissue or umbilical cord. This review discusses some of their biology and pre-clinical studies before describing the most pertinent clinical trials in this area.

Use of biologics in rotator cuff disorders: Current concept review.

Poor tendon to bone healing following rotator cuff repair has led to the continued interest and investigation into biological augmentation. The biology of tendinopathy is not fully understood and consequently the availability of disease modifying therapeutic targets is limited. A ceiling of benefit has been reached by mechanical optimisation of rotator cuff repair and thus, in order to improve healing rates, a biological solution is required. This review focuses on the strategies to biologically augment rotator cuff disorders with an emphasis on rotator cuff repair. Leucocyte rich platelet rich plasma has been shown to improve healing rates without clinically relevant improvements in outcome scores. Similarly, improved healing rates have also been reported with bone marrow stimulation and in long-term follow-up with bone marrow concentrate. Extracellular matrix (ECM) and synthetic scaffolds can increase healing through mechanical and or biological augmentation. A potential third category of scaffold is bio-inductive and has no mechanical support. Studies involving various scaffolds have shown promising results for augmentation of large to massive tears and is likely to be most beneficial when tendon quality is poor, however level I evidence is limited.

Does statin-treated hyperlipidemia affect rotator cuff healing or muscle fatty infiltration after rotator cuff repair?

BACKGROUND: Hyperlipidemia is linked to poor tendon-to-bone healing and progression of fatty infiltration after rotator cuff repair. Statins effectively treat hyperlipidemia, but it is unknown if they have any potential detrimental effects following rotator cuff repair. The aim of this study was to evaluate the effect of statins on rotator cuff healing and fatty infiltration following repair. METHODS: A total of 77 patients undergoing arthroscopic rotator cuff repair were recruited prospectively, 38 patients who were prescribed a statin for hyperlipidemia (statin group) and 39 patients who were not taking a statin (control group). Patients who did not have both preoperative and 1-year postoperative magnetic resonance imaging (MRI) scans were excluded from the study. Patient-reported outcome measures, namely the Western Ontario Rotator Cuff (WORC) index, Constant-Murley score, American Shoulder and Elbow Surgeons (ASES) score, and Disabilities of the Arm, Shoulder and Hand (DASH) score, were collected preoperatively and at 1 year. Fatty infiltration was assessed on MRI according to the Goutallier grade preoperatively and at 12 months; rotator cuff healing was assessed at 12 months according to the Sugaya classification. Following propensity score weighting to adjust for baseline imbalances, 12-month outcomes were compared between the 2 groups. RESULTS: At 12 months, all patient-reported outcome measures had improved significantly compared with baseline (WORC score, 85.9 vs. 32.5, P < .001; ASES score, 87.3 vs. 37.5, P < .001; Constant-Murley score, 77 vs. 31, P < .001; and DASH score, 13.6 vs. 61.4, P < .001). There was no significant difference in postoperative scores in the statin group vs. the control group (WORC score, 84.9 vs. 89.6, P = .94; ASES score, 87.5 vs. 86.6, P = .40; Constant-Murley score, 77 vs. 81, P = .90; and DASH score, 14.4 vs. 11.4, P = .14), and for 3 of these scores, the 95% confidence intervals excluded a clinically meaningful difference. Similarly, rotator cuff healing at 12 months and Goutallier fatty infiltration grades were comparable between the 2 groups. Retears were seen in 6 patients (15.8%) in the statin group and 8 (20.5%) in the control group. Progression of fatty infiltration was seen in 4 patients (10.5%) in the statin and 4 (10.3%) in the control group. Statin use did not demonstrate a significant association with either retear risk (P = .41) or progression of fatty atrophy (P = .69). CONCLUSION: Patient-reported outcomes, rotator cuff retear rate, and fatty infiltration on MRI at 12 months after rotator cuff repair in patients with hyperlipidemia treated with statins are similar to those in a control group.

Pro-angiogenic and osteogenic composite scaffolds of fibrin, alginate and calcium phosphate for bone tissue engineering.

Due to the limitations of bone autografts, we aimed to develop new composite biomaterials with pro-angiogenic and osteogenic properties to be used as scaffolds in bone tissue engineering applications. We used a porous, cross-linked and slowly biodegradable fibrin/alginate scaffold originally developed in our laboratory for wound healing, throughout which deposits of calcium phosphate (CaP) were evenly incorporated using an established biomimetic method. Material characterisation revealed the porous nature and confirmed the deposition of CaP precursor phases throughout the scaffolds. MC3T3-E1 cells adhered to the scaffolds, proliferated, migrated and differentiated down the osteogenic pathway during the culture period. Chick chorioallantoic membrane (CAM) assay results showed that the scaffolds were pro-angiogenic and biocompatible. The work presented here gave useful insights into the potential of these pro-angiogenic and osteogenic scaffolds for bone tissue engineering and merits further research in a pre-clinical model prior to its clinical translation.

Single-Stage Arthroscopic Cartilage Repair With Injectable Scaffold and BMAC.

Injectable scaffold augmentation is a promising modality for single-stage cartilage repair. According to published studies, cartilage repair with scaffold augmentation has improved clinical outcomes, radiological fill, and histological repair compared with microfracture alone. Injectable scaffolds have the versatility to be used in large and irregularly shaped lesions. With correct preparation, they can be applied to lesions on the femoral condyle that may be vertical, or even inverted lesions such as those in the patella. They can be combined with bone marrow aspirate concentrate (BMAC) to provide mesenchymal stem cells (MSCs), thereby avoiding the need for microfracture. This protects the subchondral plate, preventing biomechanical alteration and potentially resulting in improved long-term outcomes. In this article, we demonstrate the utility of injectable scaffolds and their combination with BMAC.

Tibial Torsion and Patellofemoral Pain and Instability in the Adult Population: Current Concept Review.

PURPOSE OF REVIEW: Tibial torsion is a recognized cause of patellofemoral pain and instability in the paediatric population; however, it is commonly overlooked in the adult population. The aim of this review article is to summarize the current best evidence on tibial torsion for the adult orthopaedic surgeon. RECENT FINDINGS: The true incidence of tibial torsion in the adult population is unknown, with significant geographical variations making assessment very difficult. CT currently remains the gold standard for quantitatively assessing the level of tibial torsion and allows assessment of any associated femoral and knee joint rotational anomalies. Surgical correction should only be considered after completion of a course of physiotherapy aimed at addressing the associated proximal and gluteal weakness. Tibial torsion greater than 30° is used as the main indicator for tibial de-rotation osteotomy by the majority of authors. In patients with associated abnormal femoral rotation, current evidence would suggest that a single-level correction of the tibia (if considered to be a dominant deformity) is sufficient in the majority of cases. Proximal de-rotational osteotomy has been more commonly reported in the adult population and confers the advantage of allowing simultaneous correction of patella alta or excessive tubercle lateralization. Previous surgery prior to de-rotational osteotomy is common; however, in patients with persistent symptoms surgical correction still provides significant benefit. Tibial torsion persists into adulthood and can play a significant role in patellofemoral pathology. A high index of suspicion is required in order to identify torsion clinically. Surgical correction is effective for both pain and instability, but results are inferior in patients with very high pain levels pre-surgery and multiple previous surgeries.

An In Vitro Study to Determine the Feasibility of Combining Bone Marrow Concentrate with BST-CarGel as a Treatment for Cartilage Repair.

OBJECTIVE: The study aims were to determine whether BST-CarGel, a chitosan scaffold for cartilage repair, can be mixed with bone marrow aspirate concentrate (BMAC) to create a cell seeded implant with comparative properties to standard BST-CarGel mixed with blood. DESIGN: Whole blood and bone marrow were harvested from 12 patients who underwent cartilage repair surgery using BMAC after informed consent. A validated in vitro testing model was used to assess the following 6 conditions: (1) BST-CarGel mixed with whole blood (CG-WB), (2) BST-CarGel mixed with bone marrow (CG-BM), (3) BST-CarGel mixed with bone marrow concentrate (CG-BMAC), (4) whole blood (WB), (5) bone marrow (BM), and (6) bone marrow concentrate and batroxobin (BMAC-BTX). Cell retention and viability within the BST-CarGel/BMAC clots were investigated. RESULTS: In our study, BM and BMAC (processed using the Harvest, SmartPrep2 system and reactivated with batroxibin) when combined with BST-CarGel produced a product that had similar clot contraction, macroscopic properties, and histological appearance to standard BSTCarGel mixed with blood. Mononucleated cells from the BMAC were retained within the scaffold and remained viable until clot dissolution in vitro. CONCLUSIONS: By combining BST-CarGel with BMAC in the manner described, bone marrow-derived mononucleated cells can be retained within the chondral defect potentially negating the need for microfracture. Further in vivo work is required to confirm these potential benefits and determine if this combination will result in more durable cartilage repair and improved clinical outcomes.

Combined bezafibrate, medroxyprogesterone acetate and valproic acid treatment inhibits osteosarcoma cell growth without adversely affecting normal mesenchymal stem cells.

Drug repurposing is a cost-effective means of targeting new therapies for cancer. We have examined the effects of the repurposed drugs, bezafibrate, medroxyprogesterone acetate and valproic acid on human osteosarcoma cells, i.e., SAOS2 and MG63 compared with their normal cell counterparts, i.e. mesenchymal stem/stromal cells (MSCs). Cell growth, viability and migration were measured by biochemical assay and live cell imaging, whilst levels of lipid-synthesising enzymes were measured by immunoblotting cell extracts. These drug treatments inhibited the growth and survival of SAOS2 and MG63 cells most effectively when used in combination (termed V-BAP). In contrast, V-BAP treated MSCs remained viable with only moderately reduced cell proliferation. V-BAP treatment also inhibited migratory cell phenotypes. MG63 and SAOS2 cells expressed much greater levels of fatty acid synthase and stearoyl CoA desaturase 1 than MSCs, but these elevated enzyme levels significantly decreased in the V-BAP treated osteosarcoma cells prior to cell death. Hence, we have identified a repurposed drug combination that selectively inhibits the growth and survival of human osteosarcoma cells in association with altered lipid metabolism without adversely affecting their non-transformed cell counterparts.

An In Vitro Comparison of the Neurotrophic and Angiogenic Activity of Human and Canine Adipose-Derived Mesenchymal Stem Cells (MSCs): Translating MSC-Based Therapies for Spinal Cord Injury.

The majority of research into the effects of mesenchymal stem cell (MSC) transplants on spinal cord injury (SCI) is performed in rodent models, which may help inform on mechanisms of action, but does not represent the scale and wound heterogeneity seen in human SCI. In contrast, SCI in dogs occurs naturally, is more akin to human SCI, and can be used to help address important aspects of the development of human MSC-based therapies. To enable translation to the clinic and comparison across species, we have examined the paracrine, regenerative capacity of human and canine adipose-derived MSCs in vitro. MSCs were initially phenotyped according to tissue culture plastic adherence, cluster of differentiation (CD) immunoprofiling and tri-lineage differentiation potential. Conditioned medium (CM) from MSC cultures was then assessed for its neurotrophic and angiogenic activity using established cell-based assays. MSC CM significantly increased neuronal cell proliferation, neurite outgrowth, and ßIII tubulin immunopositivity. In addition, MSC CM significantly increased endothelial cell migration, cell proliferation and the formation of tubule-like structures in Matrigel assays. There were no marked or significant differences in the capacity of human or canine MSC CM to stimulate neuronal cell or endothelial cell activity. Hence, this study supports the use of MSC transplants for canine SCI; furthermore, it increases understanding of how this may subsequently provide useful information and translate to MSC transplants for human SCI.

Single-Stage Autologous Chondrocyte-Based Treatment for the Repair of Knee Cartilage Lesions: Two-Year Follow-up of a Prospective Single-Arm Multicenter Study.

BACKGROUND: There is an unmet need for a single-stage cartilage repair treatment that is cost-effective and chondrocyte-based. PURPOSE: To evaluate the safety and preliminary efficacy of autologous freshly isolated primary chondrocytes and bone marrow mononucleated cells (MNCs) seeded into a PolyActive scaffold in patients with symptomatic cartilage lesions of the knee. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 40 patients with symptomatic knee cartilage lesions were treated with freshly isolated autologous chondrocytes combined with bone marrow MNCs delivered in a biodegradable load-bearing scaffold. The treatment requires only 1 surgical intervention and is potentially a cost-effective alternative to autologous chondrocyte implantation. The primary chondrocytes and bone marrow MNCs were isolated, washed, counted, mixed, and seeded into a load-bearing scaffold in the operating room. Patients were followed up at 3, 6, 12, 18, and 24 months. Primary endpoints were treatment-related adverse events up to 3 months, adverse implant effects between 3 and 24 months, and the implant success rate at 3 months as measured by lesion filling. RESULTS: Successful lesion filling (≥67% on magnetic resonance imaging) was found in 40 patients at 3 months and in 32 of the 32 patients analyzed at 24 months. Significant improvement over baseline was found for visual analog scale for pain from 3 months onward; Knee injury and Osteoarthritis Outcome Score (KOOS)-Pain and KOOS-Activities of Daily Living from 6 months onward; for KOOS-Symptoms and Stiffness, KOOS-Quality of Life and International Knee Documentation Committee from 12 months onward; and for KOOS-Sport and Recreation from 18 months onward. Hyaline-like repair tissue was found in 22 of 31 patients available for biopsy. Arthralgia and joint effusion were the most common adverse events. Scaffold delamination and adhesions led to removal of the implant in 2 patients. CONCLUSION: The treatment of knee cartilage lesions with autologous primary chondrocytes and bone marrow MNCs, both isolated and seeded into a load-bearing PolyActive scaffold within a single surgical intervention, is safe and clinically effective. Good lesion fill and sustained clinically important and statistically significant improvement in all patient-reported outcome scores were found throughout the 24-month study. Hyaline-like cartilage was observed on biopsy specimen in at least 22 of the 40 patients. REGISTRATION: NCT01041885 (ClinicalTrials.gov identifier).

Pre-screening the intrinsic angiogenic capacity of biomaterials in an optimised ex ovo chorioallantoic membrane model.

Biomaterial development for clinical applications is currently on the rise. This necessitates adequate in vitro testing, where the structure and composition of biomaterials must be specifically tailored to withstand in situ repair and regeneration responses for a successful clinical outcome. The chorioallantoic membrane of chicken embryos has been previously used to study angiogenesis, a prerequisite for most tissue repair and regeneration. In this study, we report an optimised ex ovo method using a glass-cling film set-up that yields increased embryo survival rates and has an improved protocol for harvesting biomaterials. Furthermore, we used this method to examine the intrinsic angiogenic capacity of a variety of biomaterials categorised as natural, synthetic, natural/synthetic and natural/natural composites with varying porosities. We detected significant differences in biomaterials' angiogenesis with natural polymers and polymers with a high overall porosity showing a greater vascularisation compared to synthetic polymers. Therefore, our proposed ex ovo chorioallantoic membrane method can be effectively used to pre-screen biomaterials intended for clinical application.

The Effect of Delayed Injection of Leukocyte-Rich Platelet-Rich Plasma Following Rotator Cuff Repair on Patient Function: A Randomized Double-Blind Controlled Trial.

PURPOSE: To investigate the effect of delayed application of leukocyte-rich platelet-rich plasma (PRP) on rotator cuff repair results as assessed by outcome scores and imaging at one year. METHODS: Patients with a symptomatic rotator cuff tear awaiting arthroscopic repair were approached to take part in the study. Final eligibility for the study was confirmed at the time of surgery. A total of 97 patients were randomized to an ultrasound guided injection of leukocyte-rich PRP or normal saline between 10 and 14 days postsurgery. A total of 87 patients completed clinical evaluation and underwent magnetic resonance imaging imaging at 1 year. Outcome scores included the American Shoulder and Elbow Score, Constant score, Western Ontario Rotator Cuff Index, and the Disabilities of the Arm, Shoulder and Hand Score. Structural integrity of the repair was assessed according to the Sugaya grading. Muscle fatty infiltration was assessed on magnetic resonance imaging using the Goutallier classification. RESULTS: At 1 year postsurgery, there was no significant difference between the treatment groups on any of the patient-reported outcome measures or Constant score. On postoperative imaging analysis, there was no difference in the retear rates (Sugaya 4 and 5) between the groups (21% in control group vs 15.3% in PRP group). Fatty infiltration on postoperative imaging was found to be significantly higher in the normal saline group compared with the PRP group (Kendall's tau-b P = .032). CONCLUSIONS: The delayed application of PRP postrotator cuff repair did not improve function as measured by patient-reported outcome measures and Constant score at 1 year postoperatively. LEVEL OF EVIDENCE: Level II, prospective randomized therapeutic trial.