Orthobiologics: a review.

PURPOSE: The use of biologic materials in orthopaedics (orthobiologics) has gained significant attention over the past years. To enhance the body of the related literature, this review article is aimed at summarizing these novel biologic therapies in orthopaedics and at discussing their multiple clinical implementations and outcomes. METHODS: This review of the literature presents the methods, clinical applications, impact, cost-effectiveness, and outcomes, as well as the current indications and future perspectives of orthobiologics, namely, platelet-rich plasma, mesenchymal stem cells, bone marrow aspirate concentrate, growth factors, and tissue engineering. RESULTS: Currently available studies have used variable methods of research including biologic materials as well as patient populations and outcome measurements, therefore making comparison of studies difficult. Key features for the study and use of orthobiologics include minimal invasiveness, great healing potential, and reasonable cost as a nonoperative treatment option. Their clinical applications have been described for common orthopaedic pathologies such as osteoarthritis, articular cartilage defects, bone defects and fracture nonunions, ligament injuries, and tendinopathies. CONCLUSIONS: Orthobiologics-based therapies have shown noticeable clinical results at the short- and mid-term. It is crucial that these therapies remain effective and stable in the long term. The optimal design for a successful scaffold remains to be further determined.

Mesenchymal Stem Cell Extracellular Vesicles as Adjuvant to Bone Marrow Stimulation in Chondral Defect Repair in a Minipig Model.

OBJECTIVE: This study evaluated the effects of mesenchymal stem cell-extracellular vesicles (MSC-EVs) on chondrocyte proliferation in vitro and on cartilage repair in vivo following bone marrow stimulation (BMS) of focal chondral defects of the knee. METHODS: Six adult Göttingen minipigs received 2 chondral defects in each knee. The pigs were randomized to treatment with either BMS combined with MSC-EVs or BMS combined with phosphate-buffered saline (PBS). Intraarticular injections MSC-EVs or PBS were performed immediately after closure of the surgical incisions, and at 2 and 4 weeks postoperatively. Repair was evaluated after 6 months with gross examination, histology, histomorphometry, immunohistochemistry, and micro-computed tomography (µCT) analysis of the trabecular bone beneath the defect. RESULTS: Defects treated with MSC-EVs had more bone in the cartilage defect area than the PBS-treated defects (7.9% vs. 1.5%, P = 0.02). Less than 1% of the repair tissue in both groups was hyaline cartilage. International Cartilage and Joint Preservation Society II histological scoring showed that defects treated with MSC-EVs scored lower on "matrix staining" (20.8 vs. 50.0, P = 0.03), "cell morphology" (35.4 vs. 53.8, P = 0.04), and "overall assessment" (30.8 vs. 52.9, P = 0.03). Consistently, defects treated with MSC-EVs had lower collagen II and higher collagen I areal deposition. Defects treated with MSC-EVs had subchondral bone with significantly higher tissue mineral densities than PBS-treated defects (860 mg HA/cm3 vs. 838 mg HA/cm3, P = 0.02). CONCLUSION: Intraarticular injections of MSC-EVs in conjunction with BMS led to osseous ingrowth that impaired optimal cartilage repair, while enhancing subchondral bone healing.

Nonoperative and Operative Soft-Tissue, Cartilage, and Bony Regeneration and Orthopaedic Biologics of the Shoulder: An Orthoregeneration Network (ON) Foundation Review.

Orthoregeneration is defined as a solution for orthopaedic conditions that harnesses the benefits of biology to improve healing, reduce pain, improve function, and optimally, provide an environment for tissue regeneration. Options include drugs, surgical intervention, scaffolds, biologics as a product of cells, and physical and electro-magnetic stimuli. The goal of regenerative medicine is to enhance the healing of tissue after musculoskeletal injuries as both isolated treatment and adjunct to surgical management, using novel therapies to improve recovery and outcomes. Various orthopaedic biologics (orthobiologics) have been investigated for the treatment of pathology involving the shoulder including the rotator cuff tendons, glenohumeral articular cartilage, glenoid labrum, the joint capsule, and bone. Promising and established treatment modalities include hyaluronic acid (HA); platelet-rich plasma (PRP) and platelet rich concentrates (PRC); bone marrow aspirate (BMA) comprising mesenchymal stromal cells (MSCs alternatively termed medicinal signaling cells and frequently, misleadingly labelled "mesenchymal stem cells"); MSC harvested from adipose, umbilical, or placental sources; factors including vascular endothelial growth factors (VEGF), basic fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), transforming growth factor-beta (TGFß), bone morphogenic protein (BMP), and matrix metalloproteinases (MMPs); prolotherapy; pulsed electromagnetic field therapy; microfracture and other marrow-stimulation techniques; biologic resurfacing using acellular dermal allografts, allograft Achilles tendons, allograft lateral menisci, fascia lata autografts, and porcine xenografts; osteochondral autograft or allograft); and autologous chondrocyte implantation (ACI). Studies involving hyaluronic acid, platelet rich plasma, and medicinal signaling cells of various origin tissues have shown mixed results to-date as isolated treatments and as surgical adjuncts. Despite varied results thus far, there is great potential for improved efficacy with refinement of current techniques and translation of burgeoning preclinical work. LEVEL OF EVIDENCE: Level V, expert opinion.

Five-Year Outcome of 1-Stage Cell-Based Cartilage Repair Using Recycled Autologous Chondrons and Allogenic Mesenchymal Stromal Cells: A First-in-Human Clinical Trial.

BACKGROUND: Long-term clinical evaluation of patient outcomes can steer treatment choices and further research for cartilage repair. Using mesenchymal stromal cells (MSCs) as signaling cells instead of stem cells is a novel approach in the field. PURPOSE: To report the 5-year follow-up of safety, clinical efficacy, and durability after treatment of symptomatic cartilage defects in the knee with allogenic MSCs mixed with recycled autologous chondrons in first-in-human study of 1-stage cartilage repair. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: This study is an investigator-driven study aiming at the feasibility and safety of this innovative cartilage repair procedure. Between 2013 and 2014, a total of 35 patients (mean ± SD age, 36 ± 8 years) were treated with a 1-stage cartilage repair procedure called IMPACT (Instant MSC Product Accompanying Autologous Chondron Transplantation) for a symptomatic cartilage defect on the femoral condyle or trochlear groove. Subsequent follow-up after initial publication was performed annually using online patient-reported outcome measures with a mean follow-up of 61 months (range, 56-71 months). Patient-reported outcome measures included the KOOS (Knee injury and Osteoarthritis Outcome Score), visual analog scale for pain, and EuroQol-5 Dimensions. All clinical data and serious adverse events, including additional treatment received after IMPACT, were recorded. A failure of IMPACT was defined as a chondral defect of at least 20% of the index lesion with a need for a reintervention including a surgical procedure or an intra-articular injection. RESULTS: Using allogenic MSCs, no signs of a foreign body response or serious adverse reactions were recorded after 5 years. The majority of patients showed statistically significant and clinically relevant improvement in the KOOS and all its subscales from baseline to 60 months: overall, 57.9 ± 16.3 to 78.9 ± 17.7 (P < .001); Pain, 62.3 ± 18.9 to 79.9 ± 20.0 (P = .03); Function, 61.6 ± 16.5 to 79.4 ± 17.3 (P = .01); Activities of Daily Living, 69.0 ± 19.0 to 89.9 ± 14.9 (P < .001); Sports and Recreation, 32.3 ± 22.6 to 57.5 ± 30.0 (P = .02); and Quality of Life, 25.9 ± 12.9 to 55.8 ± 26.8 (P < .001). The visual analog scale score for pain improved significantly from baseline (45.3 ± 23.6) to 60 months (15.4 ± 13.4) (P < .001). Five cases required reintervention. CONCLUSION: This is the first study showing the midterm safety and efficacy of the proof of concept that allogenic MSCs augment 1-stage articular cartilage repair. The absence of serious adverse events and the clinical outcome support the longevity of this unique concept. These data support MSC-augmented chondron transplantation (IMPACT) as a safe 1-stage surgical solution that is considerably more cost-effective and a logistically advantageous alternative to conventional 2-stage cell-based therapy for articular chondral defects in the knee.

Editorial Commentary: No Longer a Salvage Procedure: Allograft Labral Reconstruction of the Hip Rivals the Results of Labral Repair.

In the past 5 years, arthroscopic labral reconstruction of the hip has rapidly evolved from a salvage procedure used primarily in the setting of multiple failed prior hip surgical procedures to an alternative, and even preferable, primary treatment option for labral pathology and femoroacetabular impingement. As opposed to labral repair, labral reconstruction allows for complete removal of all damaged, pain-generating tissue; optimal correction of underlying bony impingement; and consistent creation of a graft that appropriately restores the fluid hip seal, improves pressurization and stabilization, and decreases contact pressure. Allograft tissue, in particular, allows for accurate and reliable graft length creation and does not rely on native tissue quality. Hips that undergo labral reconstruction have been shown to have positive outcomes at minimum 2-year follow-up, despite the fact that in many cases, these hips have more damage and a poorer preoperative prognosis. Patients report decreased pain, increased function, and greater quality of life after labral reconstruction, and this new evidence suggests that they can resume high-level physical activity as well. Circumferential labral reconstruction is no longer a salvage procedure and is an important tool for the hip arthroscopist; however, it requires high proficiency in hip arthroscopy to perform.

Histomorphometric evaluation of the effects of mandibular advancement appliance and low level laser therapy (LLLT) with different doses on condylar cartilage and subchondral bone in rats / Evaluación histomorfométrica de los efectos del aparato de avance mandibular y la terapia con láser de bajo nivel (TLBN) con diferentes dosis en cartílago condilar y hueso subcondral en ratas

The aim of this study was to evaluate the effects of mandibular advancement appliance and low level laser therapy (LLLT) with different doses on cellular hypertrophic changes in the mandibular condyle of rats. Forty-eight 8-week-old male Wistar albino rats weighing between 260 and 280 g were randomly divided into four experimental and control groups. Group I was the control group; group II was the mandibular advancement appliance group; group III was the 8 J/cm2 (0.25 W, 20 s) laser irradiation with mandibular advancement appliance group; and group IV was the 10 J/cm2 (0.25 W, 25 s) laser irradiation with mandibular advancement appliance group. Mandibular condyle cartilage and subchondral bone changes with different LLLT dose and mandibular advancement appliance were evaluated by histomorphometrical analysis. Subchondral bone fraction results showed that there were no significant differences between groups (p<0.05). The statistically significant differences found between control group and experimental groups in anterior and posterior cartilage layers thickness (p<0.05) and (p<0.01). Posterior and anterior condylar cartilage layers of rats react differentially to LLLT and mandibular advancement application. Maximum changes in condylar cartilage layers were found in 8 J/cm2 laser irradiation with mandibular appliance group.

El objetivo de este estudio fue evaluar los efectos del aparato de avance mandibular y la terapia con láser de bajo nivel (TLBN) con diferentes dosis sobre los cambios hipertróficos celulares, en el cóndilo mandibular de ratas. Cuarenta y ocho ratas albinas macho Wistar de 8 semanas de edad con un peso de 260 y 280 g se dividieron aleatoriamente en cuatro grupos experimentales y control. El grupo I control; grupo II, dispositivos de avance mandibular; grupo III de irradiación con láser de 8 J / cm2 (0.25 W, 20 s) con el grupo dispositivos de avance mandibular; y grupo IV con irradiación láser de 10 J / cm2 (0,25 W, 25 s) con el grupo de dispositivos de avance mandibular. El cartílago del cóndilo mandibular y los cambios en el hueso subcondral con diferentes dosis de TLBN y dispositivo de avance mandibular, se evaluaron mediante análisis histomorfométrico. Los resultados de la fracción ósea subcondral indicaron que no hubo diferencias significativas entre los grupos (p <0,05). Las diferencias estadísticamente significativas encontradas entre el grupo control y los grupos experimentales, en el grosor del cartílago anterior y posterior (p<0,05) y (p<0,01). Las capas de cartílago condilar posterior y anterior de las ratas reaccionan de manera diferencial a la aplicación de TLBN y avance mandibular. Se encontraron cambios significativos en las capas de cartílago condilar con irradiación láser de 8 J /cm2 con el grupo de dispositivos mandibulares.

Biological resurfacing of grade IV articular cartilage ulcers in knee joint with Hyalofast.

INTRODUCTION: Hyalofast grafting with microfracture is a new minimally invasive treatment method being proposed for joint cartilage defects. This study was done to measure the clinical efficacy of Hyalofast grafting after microfractures. METHODS: Forty-six patients were assessed for knee function using knee injury and osteoarthritis outcome score (KOOS) after undergoing microfracture and Hyalofast grafting surgery. We further divided the 46 patients into a group of 10 patients who had no associated procedures done with the microfracture and Hyalofast grafting surgery. All patients had magnetic resonance imaging (MRI) of the affected knee pre-surgery and two patients had MRI done post-surgery. Due to another unrelated injury, we were also able to obtain further arthroscopic findings of another patient's knee 18 months after microfracture and Hyalofast grafting. RESULTS: There was a statistically significant improvement in all categories of the KOOS (symptoms, pain, daily living, sports and quality of life) compared between years 1, 2 and 3 against pre-surgery. For the subgroup of Hyalofast only, there was a statistically significant improvement in symptoms, pain and daily living categories of the KOOS compared between years 1, 2 and 3 against pre-surgery. CONCLUSIONS: Our study shows that Hyalofast grafting after microfracture is a viable alternative to treatment for patients with grade 4 cartilage ulcers.

Tracking Stem Cell Implants in Cartilage Defects of Minipigs by Using Ferumoxytol-enhanced MRI.

Background Cartilage repair outcomes of matrix-associated stem cell implants (MASIs) in patients have been highly variable. Conventional MRI cannot help distinguish between grafts that will and grafts that will not repair the underlying cartilage defect until many months after the repair. Purpose To determine if ferumoxytol nanoparticle labeling could be used to depict successful or failed MASIs compared with conventional MRI in a large-animal model. Materials and Methods Between January 2016 and December 2017, 10 Göttingen minipigs (n = 5 male; n = 5 female; mean age, 6 months ± 5.1; age range, 4-20 months) received implants of unlabeled (n = 12) or ferumoxytol-labeled (n = 20) viable and apoptotic MASIs in cartilage defects of the distal femur. All MASIs were serially imaged with MRI on a 3.0-T imaging unit at week 1 and weeks 2, 4, 8, 12, and 24, with calculation of T2 relaxation times. Cartilage regeneration outcomes were assessed by using the MR observation of cartilage repair tissue (MOCART) score (scale, 0-100), the Pineda score, and histopathologic quantification of collagen 2 production in the cartilage defect. Findings were compared by using the unpaired Wilcoxon rank sum test, a linear regression model, the Fisher exact test, and Pearson correlation. Results Ferumoxytol-labeled MASIs showed significant T2 shortening (22.2 msec ± 3.2 vs 27.9 msec ± 1.8; P < .001) and no difference in cartilage repair outcomes compared with unlabeled control MASIs (P > .05). At week 2 after implantation, ferumoxytol-labeled apoptotic MASIs showed a loss of iron signal and higher T2 relaxation times compared with ferumoxytol-labeled viable MASIs (26.6 msec ± 4.9 vs 20.8 msec ± 5.3; P = .001). Standard MRI showed incomplete cartilage defect repair of apoptotic MASIs at 24 weeks. Iron signal loss at 2 weeks correlated with incomplete cartilage repair, diagnosed at histopathologic examination at 12-24 weeks. Conclusion Ferumoxytol nanoparticle labeling can accelerate the diagnosis of successful and failed matrix-associated stem cell implants at MRI in a large-animal model. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Sneag and Potter in this issue.

Matrix-associated stem cell transplantation is successful in treating talar osteochondral lesions.

PURPOSE: Osteochondral lesions (OCLs) of the talus are a challenging and increasingly recognized problem in chronic ankle pain. Many novel techniques exist to try and treat this challenging entity. Difficulties associated with treating OCLs include lesion location, size, chronicity, and problems associated with potential graft harvest sites. Matrix-associated stem cell transplantation (MAST) is one such treatment described for larger lesions > 15 mm2 or failed alternative therapies. This cohort study describes a 3 year review of the outcomes of talar lesions treated with MAST. METHODS: A review of all patients treated with MAST by a single surgeon was conducted. Pre-operative radiographs, MRIs, and FAOS outcome questionnaire scores were reviewed. Intraoperative classification was undertaken to correlate with imaging. Post-operative outcomes included FAOS scores, return to sport, revision surgery/failure of treatment, and progression to ankle fusion. RESULTS: In this study, 38 OCLs in 32 patients were identified. Median patient age was 35 years of which (68.8%) were male. Median length of follow-up was 36.7 months (range 12-64 months). (83%) returned to playing sport. Twenty-three patients underwent MAST in the setting of a failed previous operative attempt, with just nine having MAST as a first option. Nine patients out of 32 had a further procedure. Improvements were seen in all domains of the FAOS (p < 0.05). CONCLUSION: MAST has demonstrated encouraging results in lesions which prove challenging to treat, even in a "failed microfracture" cohort. LEVEL OF EVIDENCE: IV.

Clinical and radiographic outcomes of chitosan-glycerol phosphate/blood implant are similar with hyaluronic acid-based cell-free scaffold in the treatment of focal osteochondral lesions of the knee joint.

PURPOSE: To determine the clinical and radiographic efficacy of chitosan-glycerol phosphate/blood implant versus hyaluronic acid-based cell-free scaffold in patients with focal osteochondral lesion of the knee joint. METHODS: Clinical data of 46 patients surgically treated using either chitosan-glycerol phosphate/blood implant (25 patients, Group 1) or hyaluronic acid-based cell-free scaffold (21 patients, Group 2) in combination with microfracture were retrospectively evaluated. All lesions were Outerbridge grade III or IV with a mean lesion size of 3.3 ± 0.7 cm2. The mean follow-up time was 24.4 months. Visual analogue scale (VAS), Lysholm knee score, and Tegner activity scale were the instruments to evaluate the clinical status. Magnetic resonance observation of cartilage repair tissue (MOCART) system was used to analyze the characteristics of repair tissue. RESULTS: No significant differences were detected between the groups regarding VAS, Lysholm, and Tegner scores at any time interval during the whole follow-up. The mean post-operative VAS and Lysholm scores at the latest follow-up was significantly better in cases with the lesion size ≤ 3 cm2 in Group 1 (p = 0.001, p < 0.001, respectively). However, no significant differences according to the lesion size were detected in Group 2 (n.s.). Complete repair with the filling of the defect was achieved in 7 (28%) of the knees in Group 1 and it was 7 (33.3%) of the knees in Group 2 according to MOCART system at the latest follow-up. CONCLUSION: Single-stage regenerative cartilage surgery using chitosan-glycerol phosphate/blood implant combined to microfracture for focal osteochondral lesions of the knee revealed similar clinical and radiographic outcomes with hyaluronic acid-based cell-free scaffold at short-term follow-up. However, clinical outcomes of hyaluronan scaffold were less sensitive to defect size than chitosan. With the advantages of no hypertrophic repair tissue formation as well as no need to arthrotomy during surgery, chitosan is an effective choice especially in patients with the lesion size ≤ 3 cm2. LEVEL OF EVIDENCE: III.

[Subchondral drilling method combined with gum-bletilla complex to repair articular cartilage defects].

Two types(A model and B model) of articular cartilage defect models were prepared by using adult New Zealand white rabbits. A model group was applied by drilling without through subchondral bone, whose right joint was repaired by composite scaffolds made by seed cell, gum-bletilla as well as Pluronic F-127, and left side was blank control. B model group was applied by subchondral drilling method, whose right joint was repaired by using composite scaffolds made by gum-bletilla and Pluronic F-127 without seed cells, and left side was blank control. Autogenous contrast was used in both model types. In addition, another group was applied with B model type rabbits, which was repaired with artificial complex material of Pluronic F-127 in both joint sides. 4, 12 and 24 weeks after operation, the animals were sacrificed and the samples were collected from repaired area for staining with HE, typeⅡcollagen immunohistochemical method, Alcian blue, and toluidine blue, and then were observed with optical microscope. Semi-quantitative scores were graded by referring to Wakitanis histological scoring standard to investigate the histomorphology of repaired tissue. Hyaline cartilage repairing was achieved in both Group A and Group B, with satisfactory results. There were no significant differences on repairing effects for articular cartilage defects between composite scaffolds made by seed cell, gum-bletilla and Pluronic F-127, and the composite scaffolds made by gum-bletilla and Pluronic F-127 without seed cell. Better repairing effects for articular cartilage defects were observed in groups with use of gum-bletilla, indicating that gum-bletilla is a vital part in composite scaffolds material.

Outcomes of cartilage repair techniques for chondral injury in the hip-a systematic review.

OBJECTIVE/PURPOSE: The aim of the study was to assess the options of treatment and their related outcomes for chondral injuries in the hip based on the available evidence whilst highlighting new and innovative techniques. METHODS: A systematic review of the literature from PubMed (Medline), EMBASE, Google Scholar, British Nursing Index (BNI), Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Allied and Complementary Medicine Database (AMED) was undertaken from their inception to March 2017 using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Clinical outcome studies, prospective/retrospective case series and case reports that described the outcome of cartilage repair technique for the chondral injury in the hip were included. Studies on total hip replacement, animal studies, basic studies, trial protocols and review articles were excluded. RESULTS: The systematic review found 21 relevant papers with 596 hips. Over 80% of the included studies were published in or after 2010. Most studies were case series or case reports (18 studies, 85.7%). Arthroscopy was used in 11 studies (52.4%). The minimum follow-up period was six months. Mean age of the participants was 37.2 years; 93.5% of patients had cartilage injuries of the acetabulum and 6.5% of them had injuries of the femoral head. Amongst the 11 techniques described in the systematic review, autologous matrix-induced chondrogenesis, osteochondral autograft transplantation and microfracture were the three frequently reported techniques. CONCLUSION: Over ten different techniques are available for cartilage repair in the hip, and most of them have good short- to medium-term outcomes. However, there are no robust comparative studies to assess superiority of one technique over another, and further research is required in this arena.

Biophysical stimulation improves clinical results of matrix-assisted autologous chondrocyte implantation in the treatment of chondral lesions of the knee.

PURPOSE: The purpose of the present study was to evaluate the effects of pulsed electromagnetic fields (PEMFs) on clinical outcome in patients who underwent arthroscopic matrix-assisted autologous chondrocyte implantation (MACI) for chondral lesions of the knee. METHODS: Thirty patients affected by grade III and IV International Cartilage Repair Society chondral lesions of the knee underwent MACI. After surgery, patients were randomly assigned to either experimental group (PEMFs 4 h per day for 60 days) or control group . Clinical outcome was evaluated through International Knee Documentation Committee (IKDC) subjective knee evaluation form, Visual Analog Scale, Short Form-36 (SF-36) and EuroQoL before surgery and 1, 2, 6, and 60 months postoperative. RESULTS: Mean size of chondral lesion was 2.4 ± 0.6 cm2 in the PEMFs group and 2.5 ± 0.5 cm2 in the control one. No differences were found between groups at baseline. IKDC score increased in both groups till 6 months, but afterward improvement was observed only in the experimental group with a significant difference between groups at 60 months (p = 0.001). A significant difference between groups was recorded at 60 months for SF-36 (p = 0.006) and EuroQol (p = 0.020). A significant pain reduction was observed in the experimental group at 1-, 2- and 60-month follow-up. CONCLUSION: Biophysical stimulation with PEMFs improves clinical outcome after arthroscopic MACI for chondral lesions of the knee in the short- and long-term follow-up. Biophysical stimulation should be considered as an effective tool in order to ameliorate clinical results of regenerative medicine. The use of PEMFs represents an innovative therapeutic approach for the survival of cartilage-engineered constructs and consequently the success of orthopaedic surgery. LEVEL OF EVIDENCE: II.

Use of Particulated Juvenile Articular Cartilage Allograft for Osteochondral Lesions of the Wrist.

BACKGROUND: Articular cartilage injuries are a common injury among young, active patients, and the most appropriate treatment for these injuries remains controversial. A promising new technology in the treatment of high-grade cartilage injuries is particulated juvenile articular cartilage (PJAC) allograft (DeNovo NT, Zimmer, Warsaw, Indiana). This has been shown to be successful in multiple joints including the knee, talus, and elbow. No studies or case reports exist in supporting or discouraging its use in injuries of the wrist, in specific, the scaphoid. METHODS: The use of PJAC allograft is described for the treatment of an active 21-year-old male with an Outerbridge Grade IV chondral lesion on the proximal pole of his right scaphoid and right distal radius scaphoid facet who had failed conservative management. The patient was followed clinically and radiographically for 21 months. RESULTS: The patient had return to full sport (jujutsu) and full range-of-motion, both of which represented an improvement from his preoperative exam. Radiographically, the chondral lucency seen had decreased in size and was almost completely absent on radiographs after 21 months. CONCLUSIONS: The results of this case suggest that PJAC can be used safely and effectively in the wrist thereby potentially broadening the indications for its use.

Restorative Tissue Transplantation Options for Osteochondral Lesions of the Talus: A Review.

Symptomatic osteochondral lesions of the talus remain a challenging problem due to inability for cartilage lesions to heal. Numerous treatment options exist, including nonoperative management, marrow stimulating techniques, and autograft-allograft. Arthroscopic marrow stimulation forms fibrocartilage that has been shown to be biomechanically weaker than hyaline cartilage. Restorative tissue transplantation options are being used more for larger and cystic lesions. Newer biologics and particulated juvenile cartilage are currently under investigation for possible clinical efficacy. This article provides an evidenced-based summary of available literature on the use of biologics for treatment of osteochondral lesions of the talus.

Serum and synovial fluid lipidomic profiles predict obesity-associated osteoarthritis, synovitis, and wound repair.

High-fat diet-induced obesity is a major risk factor for osteoarthritis (OA) and diminished wound healing. The objective of this study was to determine the associations among serum and synovial fluid lipid levels with OA, synovitis, adipokine levels, and wound healing in a pre-clinical obese mouse model of OA. Male C57BL/6 J mice were fed either a low-fat (10% kcal) or one of three high-fat (HF, 60% kcal) diets rich in saturated fatty acids (SFAs), ω-6 or ω-3 polyunsaturated FAs (PUFAs). OA was induced by destabilization of the medial meniscus. Mice also received an ear punch for evaluating wound healing. Serum and synovial fluid were collected for lipidomic and adipokine analyses. We demonstrated that the serum levels of ω-3 PUFAs were negatively correlated with OA and wound size, but positively correlated with adiponectin levels. In contrast, most ω-6 PUFAs exhibited positive correlations with OA, impaired healing, and inflammatory adipokines. Interestingly, levels of pentadecylic acid (C15:0, an odd-chain SFA) and palmitoleic acid were inversely correlated with joint degradation. This study extends our understanding of the links of FAs with OA, synovitis and wound healing, and reports newly identified serum and synovial fluid FAs as predictive biomarkers of OA in obesity.

Mechanical Stimulation Protocols of Human Derived Cells in Articular Cartilage Tissue Engineering - A Systematic Review.

Mechanical stimulation is a key factor in articular cartilage generation and maintenance. Bioreactor systems have been designed and built in order to deliver specific types of mechanical stimulation. The focus has been twofold, applying a type of preconditioning in order to stimulate cell differentiation, and to simulate in vivo conditions in order to gain further insight into how cells respond to different stimulatory patterns. Due to the complex forces at work within joints, it is difficult to simulate mechanical conditions using a bioreactor. The aim of this review is to gain a deeper understanding of the complexities of mechanical stimulation protocols by comparing those employed in bioreactors in the context of tissue engineering for articular cartilage, and to consider their effects on cultured cells. Allied and Complementary Medicine 1985 to 2016, Ovid MEDLINE[R] 1946 to 2016, and Embase 1974 to 2016 were searched using key terms. Results were subject to inclusion and exclusion criteria, key findings summarised into a table and subsequently discussed. Based on this review it is overwhelmingly clear that mechanical stimulation leads to increased chondrogenic properties in the context of bioreactor articular cartilage tissue engineering using human cells. However, given the variability and lack of controlled factors between research articles, results are difficult to compare, and a standardised method of evaluating stimulation protocols proved challenging. With improved standardisation in mechanical stimulation protocol reporting, bioreactor design and building processes, along with a better understanding of joint behaviours, we hope to perform a meta-analysis on stimulation protocols and methods.

Biological Therapies for Cartilage Lesions in the Hip: A New Horizon.

Treatment of hip cartilage disease is challenging, and there is no clear algorithm to address this entity. Biomarkers are arising as promising diagnostic tools because they could play a role in the early assessment of the prearthritic joint and as a prognostic factor before and after treatment. The potential effect of biomarkers may be used to categorize individuals at risk of evolving to severe osteoarthritis, to develop new measures for clinical progression of the disease, and to develop new treatment options for the prevention of osteoarthritis progression. A trend toward a less invasive biological treatment will usher in a new treatment era. With the growth of surgical skills in hip arthroscopy, cartilage restoration techniques are evolving in a fast and exponential manner. Biological and surgical treatments have been proposed to treat these pathologies. Biological treatments include platelet-rich plasma, stem cells or bone marrow aspirate concentration, hyaluronic acid, losartan, and fish oil. Surgical treatments include microfracture alone or augmented, direct repair, autologous chondrocyte implantation, matrix-induced chondrocyte implantation, autologous matrix-induced chondrogenesis, mosaicplasty, osteochondral allograft transplantation, and stem cells implanted in matrix (stem cells in membranes/expanded stem cells). This article reviews new evidence available on treatment options for chondral lesions and early osteoarthritis of the hip. [Orthopedics. 2016; 39(4):e715-e723.].

Effect of highly purified capsaicin on articular cartilage and rotator cuff tendon healing: An in vivo rabbit study.

Highly purified capsaicin has emerged as a promising injectable compound capable of providing sustained pain relief following a single localized treatment during orthopedic surgical procedures. To further assess its reliability for clinical use, the potential effect of highly purified capsaicin on articular cartilage metabolism as well as tendon structure and function warrants clarification. In the current study, rabbits received unilateral supraspinatus transection and repair with a single 1 ml injection of capsaicin (R+C), PEG-only placebo (R+P), or saline (R+S) into the glenohumeral joint (GHJ). An additional group received 1 ml capsaicin onto an intact rotator cuff (I+C). At 18 weeks post-op, cartilage proteoglycan (PG) synthesis and content as well as cell viability were similar (p>0.05) across treatment groups. Biomechanical testing revealed no differences (p>0.05) among tendon repair treatment groups. Similarly, histologic features of both cartilage and repaired tendons showed minimal differences across groups. Hence, in this rabbit model, a single injection of highly purified capsaicin into the GHJ does not induce a deleterious response with regard to cartilage matrix metabolism and cell viability, or rotator cuff healing. These data provide further evidence supporting the use of injectable, highly purified capsaicin as a safe alternative for management of postoperative pain following GHJ surgery.