Autologous Cartilage Tissue Research Articles

Evaluating the Mechanical Strength of Three Dimensionally (3D) Printed Implants in Septorhinoplasty through Finite Element Analysis (FEA).

Autologous nasoseptal cartilage grafts are used to correct nasal asymmetry and deviation in rhinoplasty, but patients who have undergone multiple surgeries may have limited autologous cartilage tissue available. 3D-printed L-strut implants may address these challenges in the future, but their mechanical strength is understudied. Silk fibroin-gelatin (SFG), polycaprolactone (PCL), and polylactide (PLA) are bio-inks known for their strength. We present Finite Element Analysis (FEA) models comparing the mechanical strength of 3D-printed SFG, PCL, and PLA implants with nasoseptal cartilage grafts when autologous or allografts are not available. FEA models compared the stress and deformation responses of 3D-printed solid and scaffold implant replacements to cartilage. To simulate a daily force from overlying soft tissue, a unidirectional load was applied at the "keystone" region given its structural role and compared with native cartilaginous properties. 3D-printed solid SFG, PCL, and PLA and scaffold PCL and PLA models demonstrated lower deformations compared to cartilage. Solid SFG balanced strength and flexibility. The maximum stress was below all materials' yield stresses suggesting their deformations are unlikely permanent under a daily load. Our FEA models suggest that 3D-printed L-strut implants carry promising mechanical strength. Solid SFG's results mimicked cartilage's mechanical behavior. Thus, scaffold SFG merits further geometric optimization for potential use for cartilage substitution. 3D-printed septal cartilage replacement implants can potentially enhance surgical management of patients who lack available donor cartilage in select settings. Computational simulations can evaluate 3D-printed implant strength and their potential to replace septal cartilage in septorhinoplasty.

Комбинированные матрицы и тканевые инженерные конструкции из биополимеров в реконструктивно-восстановительной хирургии ЛОР-органов

Microtia is a combined congenital malformation with the prevalence of one case per 10,000–15,000 newborns, which accounts for 50% of all congenital malformations. Treatment of microtia is a challenging task. Numerous solutions have been proposed, however, none of these options guarantee good functional and aesthetic outcome. High hopes for solving the problem are placed on advances in reconstructive surgery. The study was aimed to determine the possibility of using advanced biocompatible endoprostheses manufactured using the tissue engineering technologies. Two closely related male 2-year-old minipigs of the Sus salvanius breed underwent implantation of bioengineered implants manufactured by combined 3D bioprinting with application of the collagen solution containing autologous cartilage tissue cells under the temporal fascia. The samples were collected 3 months later. Histological examination and immunohistochemistry showed that the implanted endoprosthesis initiated the development of regenerated connective tissue and its own vasculature in 100% of cases, thereby ensuring cell viability and integrity of biological structures; furthermore, no facts of the endoprosthesis rejection or resorption were reported. We have concluded that the developed implant manufacturing method is promising and can provide the basis for creation of domestic porous ear implants based on biocompatible polymeric materials, hydrogels, and autologous cellular material. It is necessary to further test the auricular implant using biological models.

A Systematic Review of Technique, Satisfaction, and Complications of Acellular Dermal Matrix in Rhinoplasty.

Acellular dermal matrix (ADM) is a new dermal transplant replacement material prepared from allogeneic or xenograft skin through bioengineering technology. This is provided for patients who are unwilling to kill part of their autologous cartilage or autologous dermal tissue and require rhinoplasty and improvement in the appearance of the nasal tip. This systematic review aims to introduce the main techniques of ADM for rhinoplasty and related patient satisfaction and complications to further guide doctors. Systematic reviews were conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses guidelines. The authors searched PubMed, Web of Science, Embase, and Cochrane Library using appropriate keywords. Data collected for each study included patient satisfaction and complications in addition to relevant technology. After full-text screening of inclusion and exclusion criteria, 10 studies were included, with a total of 324 patients receiving ADM with different transplantation methods. Primary rhinoplasty or secondary rhinoplasty study for dorsal ridge augmentation, smooth contour irregularities, autograft camouflage including tip grafts. The incidence of dorsal implant distortion was 0.72% in patients. The incidence of deviation was 2.17% in patients. The incidence of mild edema was 5.17% in patients. The incidence of partial resorption was 10.87% in patients. The incidence of significant resorption was 13.04% in patients. The incidence of seroma was 0.72% in patients. The incidence of partial prolapse was 0.72% in patients. The incidence of overcorrection and reoperation was 0.72% in patients. The incidence of erythema was 0.72% in patients. The incidence of undercorrection was 0.72% in patients. The incidence of infection was 0.72% in patients. The incidence of high-lying implants was 1.45% in patients. The current research results show that ADM is long-term effective in improving nasal dorsum enhancement, nasal contour deformity, and nasal tip appearance, with high patient satisfaction and low overall complication rate. Overcorrection should be considered during surgery to deal with postoperative partial absorption.

Comparative evaluation of low-cost 3D scanning devices for ear acquisition

Autologous ear reconstruction is a surgical procedure performed in the case of defects of the outer ear in which the malformed anatomy is reconstructed with autologous cartilage tissue and often involves the use of surgical guides modelled from a digital reconstruction of the ear anatomy. To obtain such three-dimensional anatomy, traditional imaging methods, which are expensive and invasive, can be replaced by professional 3D scanners or low-cost commercial devices. In this context, this paper focuses on the evaluation of two devices for the acquisition of the outer ear, the Intel® RealSense D405™ (stereo camera) and the TrueDepth camera of the iPhone® 13 (structured light camera), proposing a comparison based on four parameters: accuracy, precision, deviation range and point-to-point distance, in order to assess their usability in the medical field, and in particular in the context of autologous ear reconstruction. The results show that, despite significantly different handling of the raw data, the performance of the two devices is comparable: average accuracy is 0.76 mm for the D405 and 0.95 mm for the iPhone 13, average precision is 0.071 mm for the D405 and 0.065 mm for the iPhone 13, average range of deviation is 3.12 mm for the D405 and 3.64 mm for the iPhone 13.

Experimental Study on the Biological Outcome of Auricular Cartilage and Costal Cartilage at Different Time Periods After Autologous Cartilage Rhinoplasty.

Since autologous cartilage is a good transplant material, it is widely used in various fields of clinical medicine. In this study, we collected clinical specimens obtained at different numbers of years after transplantation and used histologic staining to explore the post-transplantation changes in auricular cartilage and costal cartilage. A retrospective analysis was performed on patients who underwent primary autologous cartilage rhinoplasty and secondary rhinoplasty from 2017 to 2021, and the remaining autologous cartilage tissue after surgery was used for histologic testing. As time progressed after transplantation, the density of costal chondrocytes decreased first and then increased, while the secretion of type II collagen and extracellular matrix both decreased slightly. There was a clear boundary between the cartilage tissue and the surrounding connective tissue, and there was no ingrowth of blood vessels in the cartilage. Auricular cartilage showed a decrease in the integrity of the matrix edge. Moreover, local fibrosis was visible, and vascular ingrowth was observed at the edge of the cartilage. The content of type II collagen first increased and then decreased, and the cell secretion function was lower than that of normal chondrocytes. The results of the study suggest that the histologic outcome of elastic cartilage after transplantation is significantly different from that of hyaline cartilage. Moreover, costal cartilage was more stable than auricular cartilage after transplantation.

A systematic review and meta-analysis of the efficacy and complication rates of augmentation rhinoplasty with autologous cartilage and silicone prosthesis.

Rhinoplasty is one of the most common operations in plastic and aesthetic surgery. Both solid silicone material and autologous cartilage (AC) tissue have their individual advantages and disadvantages. In this meta-analysis, the efficacy, complication rate of rhinoplasty with AC and silicone material were comprehensively analyzed and compared. The databases Medline, Embase, PubMed, China National Knowledge Infrastructure (CNKI) and Wanfang were searched by rapid matching of keywords to obtain randomized controlled trials related to AC rhinoplasty or silicone filled rhinoplasty, which were analyzed using the software Stata 16.0 after screening and quality assessment. A total of 1,233 patients undergoing rhinoplasty from 7 articles were included in the study. Meta-analysis showed that rhinoplasty with AC would gain more satisfaction [risk ratio (RR) =1.11; 95% confidence interval (CI): (1.02, 1.21); Z=2.413; P=0.016]. would reduce the complication rate [RR =0.34; 95% CI: (0.22, 0.52); Z=-5.010; P<0.0001], and resulting in less secondary surgery rate [RR =0.34; 95% CI: (0.18, 0.64); Z=-3.363; P=0.001] comparing to silicone prosthesis (SP) material. In rhinoplasty, the use of AC material gains more satisfaction, has less total complication rate, and results in less secondary surgery rate than silicone material. But based on the heterogeneity and publication bias in the studies, this topic still needs to be further explored by including more high-quality studies.

Facial Cartilaginous Reconstruction-A Historical Perspective, State-of-the-Art, and Future Directions.

Importance: Reconstruction of facial deformity poses a significant surgical challenge due to the psychological, functional, and aesthetic importance of this anatomical area. There is a need to provide not only an excellent colour and contour match for skin defects, but also a durable cartilaginous structural replacement for nasal or auricular defects. The purpose of this review is to describe the history of, and state-of-the-art techniques within, facial cartilaginous surgery, whilst highlighting recent advances and future directions for this continually advancing specialty.Observations: Limitations of synthetic implants for nasal and auricular reconstruction, such as silicone and porous polyethylene, have meant that autologous cartilage tissue for such cases remains the current gold standard. Similarly, tissue engineering approaches using unrelated cells and synthetic scaffolds have shown limited in vivo success. There is increasing recognition that both the intrinsic and extrinsic microenvironment are important for tissue engineering and synthetic scaffolds fail to provide the necessary cues for cartilage matrix secretion.Conclusions and Relevance: We discuss the first-in-man studies in the context of biomimetic and developmental approaches to engineering durable cartilage for clinical translation. Implementation of engineered autologous tissue into clinical practise could eliminate donor site morbidity and represent the next phase of the facial reconstruction evolution.

Extracellular matrix derived by human umbilical cord-deposited mesenchymal stem cells accelerates chondrocyte proliferation and differentiation potential in vitro.

The extracellular matrix (ECM) is a dynamic and intricate three-dimensional (3D) microenvironment with excellent biophysical, biomechanical, and biochemical properties that may directly or indirectly regulate cell behavior, including proliferation, adhesion, migration, and differentiation. Compared with tissue-derived ECM, cell-derived ECM potentially has more advantages, including less potential for pathogen transfer, fewer inflammatory or anti-host immune responses, and a closer resemblance to the native ECM microenvironment. Different types of cell-derived ECM, such as adipose stem cells, synovium-derived stem cells and bone marrow stromal cells, their effects on articular chondrocytes which have been researched. In this study, we aimed to develop a 3D cell culture substrate using decellularized ECM derived from human umbilical cord-derived mesenchymal stem cells (hUCMSCs), and evaluated the effects on articular chondrocytes. We evaluated the morphology and components of hUCMSC-derived ECM using physical and chemical methods. Morphological, histological, immunohistochemical, biochemical, and real-time PCR analyses demonstrated that proliferation and differentiation capacity of chondrocytes using the 3D hUCMSC-derived ECM culture substrate was superior to that using non-coated two-dimensional plastic culture plates. In conclusion, 3D decellularized ECM derived from hUCMSCs offers a tissue-specific microenvironment for in vitro culture of chondrocytes, which not only markedly promoted chondrocyte proliferation but also preserved the differentiation capacity of chondrocytes. Therefore, our findings suggest that a 3D cell-derived ECM microenvironment represents a promising prospect for autologous chondrocyte-based cartilage tissue engineering and regeneration. The hUCMSC-derived ECM as a biomaterial is used for the preparation of scaffold or hybrid scaffold products which need to further study in the future.

Review of an exploratory phase II FDA regulated clinical trial of a novel surgical innovation: completion of a prospective, randomized, controlled trial to compare NeoCart with the standard-of-care, microfracture, for articular cartilage repair

Background: Full thickness articular cartilage lesions cause significant morbidity, and surgical intervention is frequently applied to restore the joint surface. Current approaches of cartilage restoration have not proven to produce hyaline cartilage and have limited clinical longevity. The objective of the current study was to evaluate a novel autologous cartilage tissue implant, NeoCart, at the conclusion of the FDA-regulated exploratory phase II randomized, prospective clinical trial. The primary surgical standard-of-care, microfracture, was set by the FDA as the control. Objectives included parameter setting for the phase III trial while conducting a preliminary long-term evaluation of safety and efficacy. Methods: Patients were randomized 2:1 to NeoCart (n=21) or microfracture (n=9) surgical intervention at time of arthroscopy. Baseline demographics and patient-reported outcomes were established including: International Knee Documentation Committee (IKDC); Knee Injury and Osteoarthritis Outcome Score (KOOS) components including Pain, Activity of Daily Living, Quality of Life, Symptoms, Sports & Recreation; Short Form 36; and Visual Analog Scale Pain. Adverse events (AEs), range of motion, and patient reported outcomes were assessed annually for 5 years. Results: The treatment and control groups did not significantly differ in age, gender distribution, symptom duration, lesion size, or baseline patient reported outcomes aside from pre-surgical Visual Analog Scale Pain scores and KOOS Sports and Recreation. AE rates did not differ between treatments. The control group had greater loss to follow-up over a 5-year period. Change from baseline was significantly greater for NeoCart than for microfracture for primary end points; IKDC (1, 2 years) and KOOS Pain (1, 3, 4 years), and secondary end points; KOOS Quality of Life, Symptoms, and Sports & Recreation until 4 years. At 5 years, IKDC, KOOS Pain, Activities of Daily Living, and Quality of Life, and Short Form 36 Physical scores for both treatments improved significantly (P<0.05). Improvements for NeoCart were sustained earlier and throughout the entire study period. Conclusions: NeoCart implantation has a safety and efficacy profile supporting further consideration of this therapy in a confirmatory phase III trial for establishment as a primary cartilage injury treatment. While clinical trials for surgical interventions depend on comparison with a standard-of-care, the favorability of the control procedure, microfracture, varied over the study duration. The known short duration of microfracture’s therapeutic effect was likely associated with high loss to follow-up in the small control group. Although adequate for setting phase III parameters, this study is under-powered to clearly attribute differences in longer term efficacy. Nonetheless, preliminary results demonstrate that NeoCart may provide an alternative primary surgical option for cartilage injury with a more rapid onset of action than microfracture.

From Tissue Engineering to Regenerative Surgery

From Tissue Engineering to Regenerative Surgery

Magnetic Resonance Imaging Characterization and Clinical Outcomes After NeoCart Surgical Therapy as a Primary Reparative Treatment for Knee Cartilage Injuries

Background: Autologous cartilage tissue implants, including the NeoCart implant, are intended to repair focal articular cartilage lesions. Short-term results from United States Food and Drug Administration (FDA) phase I and phase II clinical trials indicated that the NeoCart implant was safe when surgically applied as a cell-based therapy and efficacious compared with microfracture. Hypothesis: Quantitative magnetic resonance imaging (MRI) analysis would reveal NeoCart tissue maturation through to 60-month follow-up. Study Design: Case series; Level of evidence, 4. Methods: Patients with symptomatic full-thickness cartilage lesions of the distal femoral condyle were treated with NeoCart in FDA clinical trials. Safety and efficacy were evaluated prospectively by MRI and clinical patient-reported outcomes (PROs) through to 60-month follow-up. Qualitative MRI metrics were quantified according to modified MOCART (magnetic resonance observation of cartilage repair tissue) criteria, with an independent evaluation of repair tissue signal intensity. Subjective PROs and objective range of motion (ROM) were obtained at baseline and through to 60 months. Results: Twenty-nine patients treated with NeoCart were observed over a mean of 52.0 ± 15.5 months (median, 60 months). MOCART analyses indicated significant improvement (P < .001) in cartilage quality from 3 to 24 months, with stabilization from 24 to 60 months. Signal intensity of the repair tissue evolved from hyperintense at early follow-up to isointense after 6 months and to hypointense after 24 months. The temporal progression toward hypointense T2 signals at later time points observed here indicated a further reorganization of the repair tissue toward a dense tissue that was less similar to the surrounding native tissue. However, 80% of patients showed evidence of subchondral bone changes on MRI at all time points; 4 patients (14%) showed no improvement of MRI criteria. Compared with baseline values, significant improvement (P < .001) was seen in PROs (mean [±SD] baseline to mean [±SD] final follow-up), including the International Knee Documentation Committee score (47.9 ± 17.4 to 75.5 ± 22.1), physical component summary of the Short Form–36 (40.5 ± 7.2 to 51.4 ± 8.1), and all 5 domains of the Knee injury and Osteoarthritis Outcome Score (Pain: 64.8 ± 12.1 to 86.1 ± 17.3; Activities of Daily Living: 75.5 ± 14.8 to 91.6 ± 13.8; Quality of Life: 28.6 ± 15.5 to 69.4 ± 28.0; Symptoms: 65.8 ± 13.8 to 86.6 ± 13.4; Sports and Recreation: 41.4 ± 24.3 to 72.4 ± 28.8). Significant (P < .0001) decreases from baseline scores for the visual analog scale for pain (34.6 ± 22.5) were seen by 6 months and sustained at final follow-up (14.3 ± 18.4). ROM significantly (P < .0001) improved from baseline (131.5° ± 7.9°) to final follow-up (140.7° ± 6.3°). Conclusion: Longitudinal MRI analysis demonstrated that NeoCart-based repair tissue is durable and evolves over time. For a majority of patients, this progression trended from an initial hyperintense signal to a hypointense signal at later follow-ups. Changes in radiographic measures over time corresponded with improvement in clinical measures, with maximum benefits experienced at 24-month follow-up. Similarly, clinical efficacy for the total cohort, determined by clinical outcome scores, reached a maximum at 24 months without decline to 60 months. Results from safety and exploratory clinical trials indicate that NeoCart is a safe and effective treatment for articular cartilage lesions through to 5-year follow-up. Registration: NCT00548119 (ClinicalTrials.gov identifier).

Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: an observational first-in-human trial

Articular cartilage injuries have poor repair capacity, leading to progressive joint damage, and cannot be restored predictably by either conventional treatments or advanced therapies based on implantation of articular chondrocytes. Compared with articular chondrocytes, chondrocytes derived from the nasal septum have superior and more reproducible capacity to generate hyaline-like cartilage tissues, with the plasticity to adapt to a joint environment. We aimed to assess whether engineered autologous nasal chondrocyte-based cartilage grafts allow safe and functional restoration of knee cartilage defects. In a first-in-human trial, ten patients with symptomatic, post-traumatic, full-thickness cartilage lesions (2-6 cm2) on the femoral condyle or trochlea were treated at University Hospital Basel in Switzerland. Chondrocytes isolated from a 6 mm nasal septum biopsy specimen were expanded and cultured onto collagen membranes to engineer cartilage grafts (30 × 40 × 2 mm). The engineered tissues were implanted into the femoral defects via mini-arthrotomy and assessed up to 24 months after surgery. Primary outcomes were feasibility and safety of the procedure. Secondary outcomes included self-assessed clinical scores and MRI-based estimation of morphological and compositional quality of the repair tissue. This study is registered with ClinicalTrials.gov, number NCT01605201. The study is ongoing, with an approved extension to 25 patients. For every patient, it was feasible to manufacture cartilaginous grafts with nasal chondrocytes embedded in an extracellular matrix rich in glycosaminoglycan and type II collagen. Engineered tissues were stable through handling with forceps and could be secured in the injured joints. No adverse reactions were recorded and self-assessed clinical scores for pain, knee function, and quality of life were improved significantly from before surgery to 24 months after surgery. Radiological assessments indicated variable degrees of defect filling and development of repair tissue approaching the composition of native cartilage. Hyaline-like cartilage tissues, engineered from autologous nasal chondrocytes, can be used clinically for repair of articular cartilage defects in the knee. Future studies are warranted to assess efficacy in large controlled trials and to investigate an extension of indications to early degenerative states or to other joints. Deutsche Arthrose-Hilfe.

An Autologous Tissue Implant, NeoCart, for Treatment of Hyaline Cartilage Injury in the Knee

NeoCart is an autologous cartilage tissue–engineered implant designed for use in repair of articular cartilage injuries. It uniquely combines a type I bovine-derived collagen scaffold with autogenous chondrocytes and bioreactor treatment. It is currently in the third phase of an investigational study in the United States for treatment of symptomatic articular cartilage lesions of the distal femur. This multicenter, prospective, randomized controlled trial directly compares changes of multiple patient-reported outcome measures over 3 years with a control group undergoing microfracture surgery. This article describes the study design and indications for enrollment in the phase III trial. The technical elements of NeoCart culture and production process, surgical implantation procedure, and rehabilitation guidelines are outlined. In addition, we review previously published findings from the completed phase I safety and phase II exploratory trials.

Engineered autologous cartilage tissue for nasal reconstruction after tumour resection: an observational first-in-human trial

Autologous native cartilage from the nasal septum, ear, or rib is the standard material for surgical reconstruction of the nasal alar lobule after two-layer excision of non-melanoma skin cancer. We assessed whether engineered autologous cartilage grafts allow safe and functional alar lobule restoration. In a first-in-human trial, we recruited five patients at the University Hospital Basel (Basel, Switzerland). To be eligible, patients had to be aged at least 18 years and have a two-layer defect (≥50% size of alar subunit) after excision of non-melanoma skin cancer on the alar lobule. Chondrocytes (isolated from a 6 mm cartilage biopsy sample from the nasal septum harvested under local anaesthesia during collection of tumour biopsy sample) were expanded, seeded, and cultured with autologous serum onto collagen type I and type III membranes in the course of 4 weeks. The resulting engineered cartilage grafts (25 mm × 25 mm × 2 mm) were shaped intra-operatively and implanted after tumour excision under paramedian forehead or nasolabial flaps, as in standard reconstruction with native cartilage. During flap refinement after 6 months, we took biopsy samples of repair tissues and histologically analysed them. The primary outcomes were safety and feasibility of the procedure, assessed 12 months after reconstruction. At least 1 year after implantation, when reconstruction is typically stabilised, we assessed patient satisfaction and functional outcomes (alar cutaneous sensibility, structural stability, and respiratory flow rate). Between Dec 13, 2010, and Feb 6, 2012, we enrolled two women and three men aged 76-88 years. All engineered grafts contained a mixed hyaline and fibrous cartilage matrix. 6 months after implantation, reconstructed tissues displayed fibromuscular fatty structures typical of the alar lobule. After 1 year, all patients were satisfied with the aesthetic and functional outcomes and no adverse events had been recorded. Cutaneous sensibility and structural stability of the reconstructed area were clinically satisfactory, with adequate respiratory function. Autologous nasal cartilage tissues can be engineered and clinically used for functional restoration of alar lobules. Engineered cartilage should now be assessed for other challenging facial reconstructions. Foundation of the Department of Surgery, University Hospital Basel; and Krebsliga beider Basel.

NeoCart, an Autologous Cartilage Tissue Implant, Compared with Microfracture for Treatment of Distal Femoral Cartilage Lesions

Despite introduction of autologous chondrocyte therapy for repair of hyaline articular cartilage injury in 1994, microfracture remains a primary standard of care. NeoCart, an autologous cartilage tissue implant, was compared with microfracture in a multisite prospective, randomized trial of a tissue-engineered bioimplant for treating articular cartilage injuries in the knee. Thirty patients were randomized at a ratio of two to one (two were treated with an autologous cartilage tissue implant [NeoCart] for each patient treated with microfracture) at the time of arthroscopic confirmation of an International Cartilage Repair Society (ICRS) grade-III lesion(s). Microfracture or cartilage biopsy was performed. NeoCart, produced by seeding a type-I collagen matrix scaffold with autogenous chondrocytes and bioreactor treatment, was implanted six weeks following arthroscopic cartilage biopsy. Standard evaluations were performed with validated clinical outcomes measures. Three, six, twelve, and twenty-four-month data are reported. The mean duration of follow-up (and standard deviation) was 26 ± 2 months. There were twenty-one patients in the NeoCart group and nine in the microfracture group. The mean age (40 ± 9 years), body mass index (BMI) (28 ± 4 kg/m2), duration between the first symptoms and treatment (3 ± 5 years), and lesion size (287 ± 138 mm2 in the NeoCart group and 252 ± 135 mm2 in the microfracture group) were similar between the groups. Adverse event rates per procedure did not differ between the treatment arms. The scores on the Short Form-36 (SF-36), Knee Injury and Osteoarthritis Outcome Score (KOOS) activities of daily living (ADL) scale, and International Knee Documentation Committee (IKDC) form improved from baseline (p < 0.05) to two years postoperatively in both treatment groups. In the NeoCart group, improvement, compared with baseline, was significant (p < 0.05) for all measures at six, twelve, and twenty-four months. Improvement in the NeoCart group was significantly greater (p < 0.05) than that in the microfracture group for the KOOS pain score at six, twelve, and twenty-four months; the KOOS symptom score at six months; the IKDC, KOOS sports, and visual analog scale (VAS) pain scores at twelve and twenty-four months; and the KOOS quality of life (QOL) score at twenty-four months. Analysis of covariance (ANCOVA) at one year indicated that the change in the KOOS pain (p = 0.016) and IKDC (p = 0.028) scores from pretreatment levels favored the NeoCart group. Significantly more NeoCart-treated patients (p = 0.0125) had responded to therapy (were therapeutic responders) at six months (43% versus 25% in the microfracture group) and twelve months (76% versus 22% in the microfracture group). This trend continued, as the proportion of NeoCart-treated patients (fifteen of nineteen) who were therapeutic responders at twenty-four months was greater than the proportion of microfracture-treated participants (four of nine) who were therapeutic responders at that time. This randomized study suggests that the safety of autologous cartilage tissue implantation, with use of the NeoCart technique, is similar to that of microfracture surgery and is associated with greater clinical efficacy at two years after treatment.

An Autologous Cartilage Tissue Implant NeoCart for Treatment of Grade III Chondral Injury to the Distal Femur

Background The healing potential of damaged articular cartilage is limited. The NeoCart is a tissue-engineered collagen matrix seeded with autogenous chondrocytes designed for the repair of hyaline articular cartilage. Hypothesis The NeoCart implant is well tolerated in the human knee. Study Design Case series; Level of evidence, 4. Methods Eight patients (treatment group) with full-thickness cartilage injury were treated with the NeoCart and evaluated prospectively. Autogenous chondrocytes provided by arthroscopic biopsy were seeded into a 3-dimensional type I collagen scaffold. The seeded scaffold was subjected to a tissue-engineering protocol including treatment with a bioreactor. Implantation of the prepared cartilage tissue patch was performed via miniarthrotomy and secured with a collagen bioadhesive. Evaluations through 24 months postoperatively included the subjective International Knee Documentation Committee questionnaire, visual analog scale, range of motion, and cartilage-sensitive magnetic resonance imaging (MRI), including quantitative T2 mapping. Results Pain scores after NeoCart implantation were significantly lower than baseline at 12 and 24 months after the procedure (P < .05). Improved function and motion were also noted at 24 months. Six patients had 67% to 100% defect fill at 24 months with MRI evaluation. One patient had moderate (33%-66%) defect fill, and another patient had poor (less than 33%) defect fill. Partial stratification of T2 values was observed for 2 patients at 12 months and 4 patients at 24 months. No patients experienced arthrofibrosis or implant hypertrophy. Conclusion Pain was significantly reduced 12 and 24 months after NeoCart treatment. Trends toward improved function and motion were observed 24 months after implantation. The MRI indicated implant stability and peripheral integration, defect fill without overgrowth, progressive maturation, and more organized cartilage formation.

Cartilage-like Tissue Engineering Using Silk Scaffolds and Mesenchymal Stem Cells

Silk fibroin scaffolds were studied as a new biomaterial option for tissue-engineered cartilage-like tissue. Human bone marrow-derived mesenchymal stem cells (MSCs) were seeded on silk, collagen, and crosslinked collagen scaffolds and cultured for 21 days in serum-free chondrogenic medium. Cells proliferated more rapidly on the silk fibroin scaffolds than on the collagen matrices. The total content of glycosaminoglycan deposition was three times higher on silk as compared to collagen scaffolds. Glycosaminoglycan deposition coincided with overexpression of collagen type II and aggrecan genes. Cartilage-like tissue was homogeneously distributed throughout the entire silk scaffolds, while on the collagen and crosslinked collagen systems tissue formation was restricted to the outer rim, leaving a doughnut appearance. Round or angular-shaped cells resided in deep lacunae in the silk systems and stained positively for collagen type II. The aggregate modulus of the tissue-engineered cartilage constructs was more than 2-fold higher than that of the unseeded silk scaffold controls. These results suggest that silk fibroin scaffolds are suitable biomaterial substrates for autologous cartilage tissue engineering in serum-free medium and enable mechanical improvements along with compositional features suitable for durable implants to generate or regenerate cartilage.

Gene expression profiling of human articular cartilage grafts generated by tissue engineering

Cartilage tissue engineering is applied clinically to cover and regenerate articular cartilage defects. In this study autologous human cartilage tissue engineering grafts based on bioresorbable polyglactin/polydioxanone scaffolds were analyzed on the broad molecular level. RNA from freshly isolated, primary and expanded adult articular chondrocytes and from three-dimensional cartilage grafts were used for gene expression profiling using oligonucleotide microarrays. The capacity of cartilage grafts to form cartilage matrix was evaluated after subcutaneous transplantation into nude mice. Gene expression profiling showed reproducibly the regulation of 905 genes and documented that chondrocytes undergo fundamental changes during cartilage tissue engineering regarding chondrocyte metabolism, growth, and differentiation. Three-dimensional assembly of expanded, dedifferentiated chondrocytes initiated the re-differentiation of cells that was accompanied by the reversal of the expression profile of multiple players of the transforming growth factor (TGF) signaling pathway including growth and differentiation factor-5 and inhibitor of differentiation-1 as well as by the induction of typical cartilage-related matrix genes such as type II collagen and cartilage oligomeric matrix protein. Cartilage grafts formed a cartilaginous matrix after transplantation into nude mice. Three-dimensional tissue culture of expanded articular chondrocytes initiates chondrocyte re-differentiation in vitro and leads to the maturation of cartilage grafts towards hyaline cartilage in vivo.

Treatment of articular cartilage defects in horses with polymer-based cartilage tissue engineering grafts

The objective of our study was to evaluate the integration of autologous cartilage tissue engineering transplants based on resorbable polyglactin/polydioxanone scaffolds into full-thickness cartilage defects of horses. Cartilage biopsies were taken from the non-load-bearing area of the lateral talus of the left tibiotarsal joint of eight healthy Haflinger horses. Tissue engineering cartilage transplants were generated by three-dimensional arrangement of autologous chondrocytes in biocompatible and resorbable polymer scaffolds. Full-thickness cartilage defects of 8 mm in diameter were created in the tubular bone condyle of the fetlock joint and cartilage grafts were fixed using an anchor system, while defects without grafting served as controls. After 6 and 12 months the repair tissue was evaluated histologically and showed formation of a cartilaginous tissue and good integration into the surrounding host tissue with firm bonding of the graft to the adjacent cartilage and the underlying subchondral bone. Biochemical analysis demonstrated that the content of glycosaminoglycans and hydroxyproline is comparable in repair tissue derived from treated and control defects. The use of three-dimensional autologous cartilage transplants based on resorbable polymer scaffolds ensures secure fixation, good integration of the graft into cartilage lesions, and is therefore suggested as a promising therapeutic option for the treatment of cartilage defects.

Synthesis of human cartilage using organotypic cell culture.

The limited supply of fresh autologous cartilage tissue for use in reconstructive surgery necessitates the use of vital banked allografts. A feasible in vitro production of cartilage tissue composed of living cells requires the use of modern tissue culture techniques retaining the phenotypic characteristics of chondrocytes. With this purpose in mind, human chondrocytes were isolated and cultured using different culture procedures: monolayer, suspension and agar gel. The differentiation state of chondrocytes as well as proteoglycan and collagen syntheses were assessed by histochemical and immunohistochemical methods. Whereas chondrocytes in monolayer displayed an unstable phenotype and tended to dedifferentiate, in three-dimensional culture the chondrocytes remained morphologically, phenotypically and functionally differentiated. Furthermore, an accumulation of matrix products pericellularly was observed in the agar gel. The results suggest that three-dimensional cultures in agar gel may allow the in vitro production of bioartificial cartilage for transplantation.