Defects Of Knee Research Articles

3D Bioprinted Integrated Osteochondral Scaffold-Mediated Repair of Articular Cartilage Defects in the Rabbit Knee

To demonstrate that a 3D-bioprinted integrated osteochondral scaffold can provide improved repair of articular cartilage defects in the rabbit knee compared to that reported for traditional tissue-engineering methods. Bone marrow mesenchymal stem cells were differentiated into osteoblasts and chondrocytes as seed cells and mixed with the corresponding bone and cartilage scaffold materials. An integrated osteochondral biphasic scaffold was fabricated via 3D-bioprinting technology through successive natural overlays of the printed material and used to repair full-thickness articular cartilage defects in the rabbit knee. Histological and biomechanical assessment of repaired tissue at 6 months post-transplantation showed almost complete repair of injured articular surfaces and presence of hyaline cartilage. A boundary existed between the transition and repair zones. The Wakitani histological score was 5.50 ± 2.07 points; maximum load was 183.11 ± 35.20 N. Repaired cartilage was integrated firmly with the subchondral bone and almost assimilated with surrounding cartilage and bone tissues. The 3D bioprinted integrated osteochondral scaffold achieved double bionic effects on the scaffold composition and structure, and it is expected to offer a new strategy for articular cartilage repair and regeneration.

Icariin-conditioned serum engineered with hyaluronic acid promote repair of articular cartilage defects in rabbit knees

BackgroundOsteochondral defects mostly occur as a result of trauma or articular degeneration. The poor regenerative ability of articular cartilage remains osteochondral defects are a tricky problem to deal with. The modern treatment strategies mainly focus on cartilage tissue engineering with bioactive materials. In this study, we aimed to develop icariin conditioned serum (ICS) together with hyaluronic acid (HA) and determine their ability in reparing osteochondral tissue in a critical-sized defect in rabbit knees.MethodsPrimary chondrocytes were incubated with serum conditioned with icariin at different concentrations, then cell proliferation rates and glycosaminoglycan (GAG) secretion were detected. Rabbits were treated with intra-articular injection of 0.5 mL normal saline (NS), ICS, HA and ICS + HA in the right knee joint, respectively. ICRS scores were used to assess the macroscopic cartilage regeneration. Histological and immunohistochemical analysis including H&E, Safranin O, toluidine blue and collagen II staining were used to determine the repair of cartilage and the regeneration of chondrocytes.ResultsIcariin at a low dose of 0.94 g/kg was identified to have significantly promoted the proliferation of chondrocytes and enhance the secretion of GAG. Femoral condyle from rabbits treated by ICS together with HA was observed to be integrated with native cartilage and more subchondral bone regeneration. ICS together with HA could promote repair of the cartilage defect and increase the neoformation of cartilage.ConclusionsThese results demonstrated the potential of ICS combined with HA to promote reparative response in cartilage defects and the possible application in bioactive material based cartilage regeneration therapies.

MaioRegen Osteochondral Substitute for the Treatment of Knee Defects: A Systematic Review of the Literature.

Background: This study aims to investigate the clinical and radiological efficacy of three-dimensional acellular scaffolds (MaioRegen) in restoring osteochondral knee defects. Methods: MEDLINE, Scopus, CINAHL, Embase, and Cochrane Databases were searched for articles in which patients were treated with MaioRegen for osteochondral knee defects. Results: A total of 471 patients were included in the study (mean age 34.07 ± 5.28 years). The treatment involved 500 lesions divided as follows: 202 (40.4%) medial femoral condyles, 107 (21.4%) lateral femoral condyles, 28 (5.6%) tibial plateaus, 46 (9.2%) trochleas, 74 (14.8%) patellas, and 43 (8.6%) unspecified femoral condyles. Mean lesion size was 3.6 ± 0.85 cm2. Only four studies reported a follow-up longer than 24 months. Significant clinical improvement has been reported in almost all studies with further improvement up to 5 years after surgery. A total of 59 complications were reported of which 52 (11.1%) experienced minor complications and 7 (1.48%) major complications. A total of 16 (3.39%) failures were reported. Conclusion: This systematic review describes the current available evidence for the treatment of osteochondral knee defects with MaioRegen Osteochondral substitute reporting promising satisfactory and reliable results at mid-term follow-up. A low rate of complications and failure was reported, confirming the safety of this scaffold. Considering the low level of evidence of the study included in the review, this data does not support the superiority of the Maioregen in terms of clinical improvement at follow-up compared to conservative treatment or other cartilage techniques.

Repair of Osteochondral Defects in Rabbit Knee Using Menstrual Blood Stem Cells Encapsulated in Fibrin Glue: A Good Stem Cell Candidate for the Treatment of Osteochondral Defects.

In recent years, researchers discovered that menstrual blood-derived stem cells (MenSCs) have the potential to differentiate into a wide range of tissues including the chondrogenic lineage. In this study, we aimed to investigate the effect of MenSCs encapsulated in fibrin glue (FG) on healing of osteochondral defect in rabbit model. We examined the effectiveness of MenSCs encapsulated in FG in comparison with FG alone in the repair of osteochondral defect (OCD) lesions of rabbit knees after 12 and 24weeks. Macroscopical evaluation revealed that the effectiveness of MenSCs incorporation with FG is much higher than FG alone in repair of OCD defects. Indeed, histopathological evaluation of FG + MenSCs group at 12weeks post-transplantation demonstrated that defects were filled with hyaline cartilage-like tissue with proper integration, high content of glycosaminoglycan and the existence of collagen fibers especially collagen type II, as well as by passing time (24weeks post-transplantation), the most regenerated tissue in FG + MenSCs group was similar to hyaline cartilage with relatively good infill and integration. As the same with the result of 12weeks post-implantation, the total point of microscopical examination in FG + MenSCs group was higher than other experimental groups, however, no significant difference was detected between groups at 24weeks (p>0.05). In summary, MenSCs as unique stem cell population, is suitable for in vivo repair of OCD defects and promising for the future clinical application.

Comparison of Undifferentiated Versus Chondrogenic Predifferentiated Mesenchymal Stem Cells Derived From Human Umbilical Cord Blood for Cartilage Repair in a Rat Model

Background: Human umbilical cord blood–derived mesenchymal stem cells (hUCB-MSCs) have gained much interest as a promising cell source for regenerative medicine owing to the noninvasive collection, availability, high expansion capacity, and low immunogenicity. However, few in vivo studies have reported the use of hUCB-MSCs on cartilage repair. Moreover, little study has been conducted on the effects of chondrogenic predifferentiation of hUCB-MSCs on cartilage repair. Purpose: To compare the effectiveness of transplanting undifferentiated versus chondrogenic predifferentiated mesenchymal stem cells (MSCs) for treating osteochondral defects. Study Design: Controlled laboratory study. Methods: Critical-sized osteochondral defects were created in the trochlear grooves of rat femurs. In 20 rats, a composite of chondrogenic predifferentiated hUCB-MSCs (chondro-MSCs) and 4% hyaluronic acid (HA) hydrogel was transplanted into defects in the right knees, whereas undifferentiated hUCB-MSCs (undiff-MSCs) and 4% HA hydrogel were transplanted into the left knees. In the control groups, 4% HA hydrogel without MSCs was transplanted into defects in the right knees, and the defects in the left knees were left untreated in 20 rats. The cartilage repair was evaluated at 8 and 16 weeks after surgery. Results: Transplanting undiff-MSCs resulted in overall superior cartilage repair as compared with chondro-MSCs, HA alone, or no treatment. The articular surfaces of the defect sites in the undiff-MSC group were relatively smoother than those of the other treatments. The undiff-MSC group showed cellular morphology and arrangement similar to surrounding normal articular cartilage tissue at 16 weeks, both of which were also better than those of the other groups. In addition, the undiff-MSC group showed coloration similar to surrounding normal articular cartilage tissue at 16 weeks in safranin O and type II collagen immunohistochemical staining. The histological scores also revealed that cartilage repair with undiff-MSCs was better than that with chondro-MSCs, HA alone, or no treatment (P < .05 in all). Conclusion: This study demonstrated that treatment with undiff-MSCs resulted in more favorable cartilage repair than that with chondro-MSCs in a rat model. These findings indicate that chondrogenic predifferentiation of MSCs before transplantation does not enhance cartilage repair. Clinical Relevance: The results of this study support the use of undifferentiated MSCs, rather than chondrogenic predifferentiated MSCs, as a stem cell therapy strategy for cartilage repair.

Similar regeneration of articular cartilage defects with autologous & allogenic chondrocytes in a rabbit model.

Background & objectives:Articular cartilage defects in the knee have a very poor capacity for repair due to avascularity. Autologous chondrocyte transplantation (ACT) is an established treatment for articular cartilage defects. Animal studies have shown promising results with allogenic chondrocyte transplantation since articular cartilage is non-immunogenic. In addition to being economical, allogenic transplantation has less morbidity compared to ACT. This study was undertaken to compare ACT with allogenic chondrocyte transplantation in the treatment of experimentally created articular cartilage defects in rabbit knee joints.Methods:Cartilage was harvested from the left knee joints of six New Zealand white rabbits (R1-R6). The harvested chondrocytes were cultured to confluence and transplanted onto a 3.5 mm chondral defect in the right knees of 12 rabbits [autologous in 6 rabbits (R1-R6) and allogenic in 6 rabbits (R7-R12)]. After 12 wk, the rabbits were euthanized and histological evaluation of the right knee joints were done with hematoxylin and eosin and safranin O staining. Quality of the repair tissue was assessed by the modified Wakitani histological grading scale.Results:Both autologous and allogenic chondrocyte transplantation resulted in the regeneration of hyaline/mixed hyaline cartilage. The total histological scores between the two groups showed no significant difference.Interpretation & conclusions:Allogenic chondrocyte transplantation seems to be as effective as ACT in cartilage regeneration, with the added advantages of increased cell availability and reduced morbidity of a single surgery.

Arthroscopic treatment of osteochondral knee defects with resorbable biphasic synthetic scaffold: clinical and radiological results and long-term survival analysis.

The aim of our study is to evaluate the long-term results in patients treated with a fully arthroscopic TruFit system for osteochondral lesions of the femoral condyle, analyzing the clinical and radiological outcomes, survival rate, complications, and correlations. The study included all patients treated with the TruFit system with a full-thickness focal lesion of the knee cartilage (grade IV according to the ICRS classification), entirely arthroscopically with a minimum follow-up of fiveyears. All patients were evaluated clinically prior to surgery (T0) and at two consecutive follow-ups (T1 36.4 ± 17.03months and T2 101.63 ± 19.02months), using the Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Hospital for Special Surgery Score (HSS). At the final follow-up, the magnetic resonance imaging (MRI) was evaluated by two orthopaedists using the magnetic resonance observation of cartilage repair tissue (MOCART) score. The sample was formed of 21 patients, of which 14 were males (67%) and 7 females (33%), with a mean age of 51.29 ± 10.70. Of the 21 patients, two underwent prosthetic knee replacement at 24 and 65months, respectively. At T0, the HSS and the KOOS score were, respectively, 60.71 ± 11.62 and 57.71 ± 6.11. For both clinical values, a significant improvement was noted between T0 and T1 (p < 0.05) and between T0 and T2 (p < 0.05). At the final follow-up, the MOCART value was found to be 45.78 ± 5.27. The study results highlighted the safety and potential of the arthroscopic TruFit system procedure, which offered a good clinical outcome with stable results at long-term follow-up although we found no correlations between the MRI and clinical results.

Sizable Scaffold-Free Tissue-Engineered Articular Cartilage Construct for Cartilage Defect Repair.

This study introduces an implantable scaffold-free cartilage tissue construct (SF) that is composed of chondrocytes and their self-produced extracellular matrix (ECM). Chondrocytes were grown in vitro for up to 5 weeks and subjected to various assays at different time points (1, 7, 21, and 35 days). For in vivo implantation, full-thickness defects (n = 5) were manually created on the trochlear groove of the both knees of rabbits (16-week old) and 3 week-cultured SF construct was implanted as an allograft for a month. The left knee defects were implanted with 1, 7, and 21 days in vitro cultured scaffold-free engineered cartilages. (group 2, 3, and 4, respectively). The maturity of the engineered cartilages was evaluated by histological, chemical and mechanical assays. The repair of damaged cartilages was also evaluated by gross images and histological observations at 4, 8, and 12 weeks postsurgery. Although defect of groups 1, 2, and 3 were repaired with fibrocartilage tissues, group 4 (21 days) showed hyaline cartilage in the histological observation. In particular, mature matrix and columnar organization of chondrocytes and highly expressed type II collagen were observed only in 21 days in vitro cultured SF cartilage (group 4) at 12 weeks. As a conclusion, cartilage repair with maturation was recapitulated when implanted the 21 day in vitro cultured scaffold-free engineered cartilage. When implanting tissue-engineered cartilage, the maturity of the cartilage tissue along with the cultivation period can affect the cartilage repair.

Surgical treatment of chondral knee defects using a collagen membrane – autologus matrix-induced chondrogenesis

ObjectivesTo evaluate the clinical and functional results of patients diagnosed with full-thickness chondral defects on symptomatic knees who underwent a biological repair technique using autologous matrix-induced chondrogenesis. MethodsSeven patients who underwent surgical treatment due to chondral lesions in the knee by autologous matrix-induced chondrogenesis were evaluated. The Lysholm, Kujala and visual analog scale of pain questionnaires were applied before and 12 months after the surgery. Nuclear magnetic resonance images were evaluated 12 months after surgery according to MOCART (magnetic resonance observation of cartilage repair tissue) cartilage repair tissue score. ResultsOf the seven patients evaluated, three presented defects classified as grade III and four as grade IV according to the International Cartilage Repair Society classification. Chondral defects were located in the medial femoral condyle (n=2), patella (n=2), and trochlea (n=3). The mean age of the patients (six men and one woman) was 37.2 years (24–54 years). The mean chondral defect size was 2.11cm2 (1.0–4.6cm2). After 12 months, post-operative nuclear magnetic resonance showed resurfacing of the lesion site with scar tissue less thick than normal cartilage in all patients. The mean MOCART score was 66.42 points. A significant decrease in pain and an improvement in the Lysholm and Kujala scores were observed. ConclusionThe use of the collagen I/III porcine membrane was favorable for the treatment of chondral and osteochondral lesions of the knee when assessing the results using the VAS, Lysholm, and Kujala scores 1 year after surgery, as well as when assessing the magnetic resonance image of the lesion 6 months after surgery.

Injectable gellan-gum/hydroxyapatite-based bilayered hydrogel composites for osteochondral tissue regeneration

Multilayer systems capable of simultaneous dual tissue formation are crucial for regeneration of the osteochondral (OC) unit. Despite the tremendous effort in the field there is still no widely accepted system that stands out in terms of superior OC regeneration. Herein, we developed bilayered hydrogel composites (BHC) combining two structurally stratified layers fabricated from naturally derived and synthetic polymers, gellan-gum (GG) and hydroxyapatite (HAp), respectively. Two formulations were made from either low acyl GG (LAGG) alone or in combination with high acyl GG (HAGG) for the cartilage-like layer. Four bone-like layers were made of LAGG incorporating different ratios of hydroxyapatite (HAp). BHC were assembled in one single construct resulting in eight distinct bilayered constructs. Architectural observations by stereomicroscope and micro-CT (μ-CT) demonstrated a connected stratified structure with good ceramic dispersion within the bone-like layer. Swelling and degradation tests as well mechanical analyse showed a stable viscoelastic construct under dynamic forces. In-vitro studies by encapsulating rabbit's chondrocytes and osteoblasts in the respective layers showed the cytocompatibility of the BHC. Further studies comprising subcutaneous implantation in mice displayed a weak immune response after four weeks. OC orthotopic defects in the rabbit's knee were created and injected with the acellular BHC. OC tissue was regenerated four weeks after implantation as confirmed by cartilaginous and bony tissue formation assessed by histologic staining and μ-CT analysis. The successful fabrication of injectable BHC and their in-vitro and in-vivo performance may be seen as advanced engineered platforms to treat the challenging OC defects.

Effects of press-fit biphasic (collagen and HA/βTCP) scaffold with cell-based therapy on cartilage and subchondral bone repair knee defect in rabbits.

Human spontaneous osteonecrosis of the knee (SPONK) is still challenging as the current treatments do not allow the production of hyaline cartilage tissue. The aim of the present study was to explore the therapeutic potential of cartilage regeneration using a new biphasic scaffold (type I collagen/hydroxyapatite) previously loaded or not with concentrated bone marrow cells. Female rabbits were operated of one knee to create articular lesions of the trochlea (three holes of 4 × 4mm). The holes were left empty in the control group or were filled with the scaffold alone or the scaffold previously loaded with concentrated bone marrow cells. After twomonths, rabbits were sacrificed and the structure of the newly formed tissues were evaluated by macroscopic, MRI, and immunohistochemistry analyses. Macroscopic and MRI evaluation of the knees did not show differences between the three groups (p > 0.05). However, histological analysis demonstrated that a higher O'Driscoll score was obtained in the two groups treated with the scaffold, as compared to the control group (p < 0.05). The number of cells in treated area was higher in scaffold groups compared to the control group (p < 0.05). There was no difference for intensity of collagen type II between the groups (p > 0.05) but subchondral bone repair was significantly thicker in scaffold-treated groups than in the control group (1mm for the control group vs 2.1 and 2.6mm for scaffold groups). Furthermore, we observed that scaffolds previously loaded with concentrated bone marrow were more reabsorbed (p < 0.05). The use of a biphasic scaffold previously loaded with concentrated bone marrow significantly improves cartilage lesion healing.

Reconstruction of Knee Defects Using Pedicled Gastrocnemius Muscle Flap with Split-Thickness Skin Grafting: A Single Surgeon's Experience with 21 Patients.

Generally, reconstruction of knee defects with exposed bone, joint, tendon, and/or hardware requires a vascularized muscle flap for coverage. Although there are several surgical options for a knee defect reconstruction, the pedicled gastrocnemius muscle still remains the workhorse flap. Although this flap is commonly used for knee defect reconstruction and the technique is described very well, there is an absence of information in the literature detailing the technique of harvesting and insetting of the gastrocnemius flap step by step with illustrations. The purpose of this article is to describe in detail the technique to reconstruct defects of the knee with pedicled gastrocnemius muscle flap as well as to present demographics and surgical results of 21 patients who had knee reconstruction with a pedicled gastrocnemius muscle flap and split-thickness skin grafting.

Healing of Osteochondral Defects Implanted with Biomimetic Scaffolds of Poly(ε-Caprolactone)/Hydroxyapatite and Glycidyl-Methacrylate-Modified Hyaluronic Acid in a Minipig.

Articular cartilage is a structure lack of vascular distribution. Once the cartilage is injured or diseased, it is unable to regenerate by itself. Surgical treatments do not effectively heal defects in articular cartilage. Tissue engineering is the most potential solution to this problem. In this study, methoxy poly(ethylene glycol)-block-poly(ε-caprolactone) (mPEG-PCL) and hydroxyapatite at a weight ratio of 2:1 were mixed via fused deposition modeling (FDM) layer by layer to form a solid scaffold. The scaffolds were further infiltrated with glycidyl methacrylate hyaluronic acid loading with 10 ng/mL of Transforming Growth Factor-β1 and photo cross-linked on top of the scaffolds. An in vivo test was performed on the knees of Lanyu miniature pigs for a period of 12 months. The healing process of the osteochondral defects was followed by computer tomography (CT). The defect was fully covered with regenerated tissues in the control pig, while different tissues were grown in the defect of knee of the experimental pig. In the gross anatomy of the cross section, the scaffold remained in the subchondral location, while surface cartilage was regenerated. The cross section of the knees of both the control and experimental pigs were subjected to hematoxylin and eosin staining. The cartilage of the knee in the experimental pig was partially matured, e.g., few chondrocyte cells were enclosed in the lacunae. In the knee of the control pig, the defect was fully grown with fibrocartilage. In another in vivo experiment in a rabbit and a pig, the composite of the TGF-β1-loaded hydrogel and scaffolds was found to regenerate hyaline cartilage. However, scaffolds that remain in the subchondral lesion potentially delay the healing process. Therefore, the structural design of the scaffold should be reconsidered to match the regeneration process of both cartilage and subchondral bone.

Matrix-Applied Characterized Autologous Cultured Chondrocytes Versus Microfracture: Five-Year Follow-up of a Prospective Randomized Trial

Background: Matrix-based cell therapy improves surgical handling, increases patient comfort, and allows for expanded indications with better reliability within the knee joint. Five-year efficacy and safety of autologous cultured chondrocytes on porcine collagen membrane (MACI) versus microfracture for treating cartilage defects have not yet been reported from any randomized controlled clinical trial. Purpose: To examine the clinical efficacy and safety results at 5 years after treatment with MACI and compare these with the efficacy and safety of microfracture treatment for symptomatic cartilage defects of the knee. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: This article describes the 5-year follow-up of the SUMMIT (Superiority of MACI Implant Versus Microfracture Treatment) clinical trial conducted at 14 study sites in Europe. All 144 patients who participated in SUMMIT were eligible to enroll; analyses of the 5-year data were performed with data from patients who signed informed consent and continued in the Extension study. Results: Of the 144 patients randomized in the SUMMIT trial, 128 signed informed consent and continued observation in the Extension study: 65 MACI (90.3%) and 63 microfracture (87.5%). The improvements in Knee injury and Osteoarthritis Outcome Score (KOOS) Pain and Function domains previously described were maintained over the 5-year follow-up. Five years after treatment, the improvement in MACI over microfracture in the co-primary endpoint of KOOS pain and function was maintained and was clinically and statistically significant (P = .022). Improvements in activities of daily living remained statistically significantly better (P = .007) in MACI patients, with quality of life and other symptoms remaining numerically higher in MACI patients but losing statistical significance relative to the results of the SUMMIT 2-year analysis. Magnetic resonance imaging (MRI) evaluation of structural repair was performed in 120 patients at year 5. As in the 2-year SUMMIT (MACI00206) results, the MRI evaluation showed improvement in defect filling for both treatments; however, no statistically significant differences were noted between treatment groups. Conclusion: Symptomatic cartilage knee defects 3 cm2 or larger treated with MACI were clinically and statistically significantly improved at 5 years compared with microfracture treatment. No remarkable adverse events or safety issues were noted in this heterogeneous patient population.

Transplantation of dedifferentiated fat cell-derived micromass pellets contributed to cartilage repair in the rat osteochondral defect model

Mature adipocyte-derived dedifferentiated fat (DFAT) cells possesses the ability to proliferate effectively and the potential to differentiate into multiple linages of mesenchymal tissue; similar to adipose-derived stem cells (ASCs). The purpose of this study is to examine the effects of DFAT cell transplantation on cartilage repair in a rat model of osteochondral defects. Full-thickness osteochondral defects were created in the knees of Sprague-Dawley rats bilaterally. Cartilage-like micromass pellets were prepared from green fluorescent protein (GFP)-labeled rat DFAT cells and subsequently transplanted into the affected right knee of these rats. Defects in the left knee were used as a control. Macroscopic and microscopic changes of treated and control defects were evaluated up to 12 weeks post-treatment with DFAT cells. To observe the transplanted cells, sectioned femurs were immunostained for GFP and type II collagen. DFAT cells formed micromass pellets expressing characteristics of immature cartilage invitro. In the DFAT cell-transplanted limbs, the defects were completely filled with white micromass pellets as early as 2 weeks post-treatment. These limbs became smooth at 4 weeks. Conversely, the defects in the control limbs were still not repaired by 4 weeks. Macroscopic ICRS scores at 2 and 4 weeks were significantly higher in the DFAT cells-transplanted limbs compared to those of the control limbs. The modified O'Driscol histological scores for the DFAT cell-transplanted limbs were significantly higher than those of the control limbs at corresponding time points. GFP-positive DAFT cells were detected in the transplanted area at 2 weeks but hardly visible at 12 weeks post-operation. Transplantation of DFAT cell-derived micromass pellets contribute to cartilage repair in a rat osteochondral defect model. DFAT cell transplantation may be a viable therapeutic strategy for the repair of osteochondral injuries.

Osteochondral tissue engineering based on biomimetic osteochondral scaffold contained calcified cartilage layer com-pounding with ADSCs in vivo

Objective The biomimetic osteochondral scaffold contained calcified cartilage layer(CCL) was fabricated us-ing slik fibroin (SF) and hydroxyapatite (HA) for materials. To investigate effects of biomimetic osteochondral scaffold contained CCL compounding with ADSCs on regeneration of the osteochondral defect on the rabbit knee, explore the feasibility of this design as a concept of osteochondral tissue engineering. Methods We fabricated a novel biomimetic osteochondral scaffold with CCL using SF and HA by the combination of paraffin-sphere leaching and modified temperature gradient-guided thermal-induced phase separation (TIPS) technique. The pore size, porosity, and compressive modulus of elasticity of the scaffold cartilage layer and the osteogenic layer were measured by scanning electron microscopy and microscopy CT. The osteochondral defect model on rabbit bi-lateral knees were established, and implanted with the non-CCL group (non-CCL scaffold compounding with ADSCs) and CCL group (CCL scaffold compounding with ADSCs). At 4, 8 and 12 weeks after implantation, the rabbits were euthanized, respectively.Gross observation score, histological and immunohistochemical assessment, biochemical quantitative of new osteochondral tissue, micro-CT scans for new bone, were executed. We evaluated the regeneration of osteochondral defects in each group, and verified the role of CCL in vivo. Results The biomimetic osteochondral scaffold with CCL had a consecutively overlapping trilayer struc-ture with different densities and pore structures, including a chondral layer (top layer), intermediate layer and bony layer (bottom layer). The cartilage layer had a well-oriented microporous structure with a uniform distribution with a pore size of (112.43±12.65) μm and a porosity of 90.25%±2.05%. The subchondral bone layer had a good three-dimensional macroporous structure, good con-nectivity, pore size (362.23±26.52) μm, porosity of osteogenic layer was 85.30%±1.80%. The cartilage regeneration in CCL+AD-SCs group was better than non-CCL+ADSCs group. The content of GAG and type II collagen in new cartilage tissue in CCL+AD-SCs group was much more than non-CCL+ADSCs group. The new bone tissue analysis and biomechanical testing had no signifi-cant differences between the two groups. Conclusion The biomimetic osteochondral SF/HA scaffold contained CCL mimics the structure of normal osteochondral tissue with good 3-dimensional pore structure and biocompatibility. The scaffold complex autolo-gous ADSCs successfully repair osteochondral defects in rabbit knee, and the presence of CCL accelerates the growth of cartilage. Key words: Tissue engineering; Cartilage; Tissue scaffolds; Slik; Hydroxyapatites

Microfractures and hydrogel scaffolds in the treatment of osteochondral knee defects: A clinical and histological evaluation

BackgroundOsteochondral knee defects (OCD) are often symptomatic, causing pain and functional impairment even in young and active patients. Regenerative surgical options, aiming to stimulate natural cartilage healing, have been recently used as a first line treatment. In this study, a new hydrogel is investigated in its capacity to regenerate the ultra-structural quality of hyaline cartilage when combined with a classical microfracture technique. Material and methodsForty-six patients, affected by grade III and IV knee chondropathies, were consecutively treated between 2013 and 2015 with microfractures followed by application of a modern hydrogel in the lesion site. All patients underwent clinical evaluation (WOMAC) pre-operatively, at 6,12 and at 24 months postoperatively: the results were compared with a subsequent, consecutive, matched, control group of 23 patients treated with microfractures alone. In a parallel and separate in-vitro histological study, adipose derived mesenchymal stem cells (ADMSCs) were encapsulated in the hydrogel scaffold, induced to differentiation into chondrocytes, and observed for a 3 weeks period. ResultsThe initial WOMAC score of 58.6 ± 11.0 in the study group was reduced by 88% at 6 months (7.1 ± 9.2) and 95% at 24 months (2.9 ± 5.9). The “in-vitro” study revealed a histological characterization typical of hyaline cartilage in study group. Separate biopsies performed at 12 months post-op in the study group also revealed type 2 collagen and hyaline-like cartilage in the regenerated tissue. ConclusionOur study demonstrated high patient satisfaction rates after microfractures combined with a modern hydrogel scaffold; histologic evaluation supported the hypothesis of creating an enhanced chondrogenic environment. Microfracture “augmentation” using modern acellular biomaterials, like hydrogels, might improve the clinical outcomes of this classical bone marrow stimulating procedure.

Impact of broad regulatory regions on Gdf5 expression and function in knee development and susceptibility to osteoarthritis

ObjectivesGiven the role of growth and differentiation factor 5 (GDF5) in knee development and osteoarthritis risk, we sought to characterise knee defects resulting from Gdf5 loss of function and how...

Ostrvasti miokutani medijalni gastroknemijus režanj u rekonstrukciji kolena i proksimalnog dela potkolenice

Ostrvasti miokutani medijalni gastroknemijus režanj u rekonstrukciji kolena i proksimalnog dela potkolenice

PP08 Health Technology Assessment Of Autologous Chondrocyte Implantation

Introduction:Microfracture (MF) has been the main intervention in symptomatic articular cartilage knee defects. Autologous chondrocyte implantation (ACI) has looked promising, but was not recommended by the UK National Institute for Health and Care Excellence (NICE) in 2015 due to the short-term follow-up data from trials.Methods:Most long-term data comes from observational studies. We provided new unpublished analyses to NICE based on survival data of these studies, with appropriate caveats. They included: a large ACI study by Nawaz with useful subgroup data by osteoarthritis Kellgren-Lawrence stage and previous repair attempts; a very large MF study by Layton, and a small RCT by Knutsen indicating MF was as ‘good’ as ACI. A Markov model explored the cost-effectiveness of ACI vs. MF. Different scenarios were explored: ACI or MF as a first procedure, followed by ACI or MF in those needing a second repair. A NHS England perspective was adopted. Health outcomes were expressed as quality-adjusted life-years (QALYs).Results:The revised base-case analysis, used a list price of £16,000 (EUR 17,380 in 2013 prices) for cells, used ACI failure data from Nawaz with no previous procedures for ACI, and pooled MF failure data from two studies-Saris and Knutsen. ACI was more expensive but provided more QALYs. The incremental cost-effectiveness ratio comparing ACI then MF with MF then ACI was £8,000 (EUR 8,690) per QALY. Various sensitivity analyses were conducted assuming a threshold of £20,000 (EUR 21,730) per QALY: previous repair attempts reduced success of ACI (£22,000 (EUR 23,900) per QALY); reducing cell costs, ACI improved its cost-effectiveness; and limiting intervention to patients with higher Kellgren-Lawrence score did not appear cost-effectiveness.Conclusions:The final NICE guidance published in October 2017 approved the use of ACI for patients who had no previous knee repairs, for people with minimal osteoarthritic damage to the knee, and for people with articular defects of over 2cm2.