Full-thickness Articular Cartilage Defects Research Articles

Catalpol promotes articular cartilage repair by enhancing the recruitment of endogenous mesenchymal stem cells.

Articular cartilage defect is challenged by insufficient regenerative ability of cartilage. Catalpol (CA), the primary active component of Rehmanniae Radix, could exert protective effects against various diseases. However, the impact of CA on the treatment of articular cartilage injuries is still unclear. In this study, full-thickness articular cartilage defect was induced in a mouse model via surgery. The animals were intraperitoneally injected with CA for 4 or 8 weeks. According to the results of macroscopic observation, micro-computed tomography CT (μCT), histological and immunohistochemistry staining, CA treatment could promote mouse cartilage repair, resulting in cartilage regeneration, bone structure improvement and matrix anabolism. Specifically, an increase in the expression of CD90, the marker of mesenchymal stem cells (MSCs), in the cartilage was observed. In addition, we evaluated the migratory and chondrogenic effects of CA on MSCs. Different concentration of CA was added to C3H10 T1/2 cells. The results showed that CA enhanced cell migration and chondrogenesis without affecting proliferation. Collectively, our findings indicate that CA may be effective for the treatment of cartilage defects via stimulation of endogenous MSCs.

All-Arthroscopic Matrix-Associated Autologous Chondrocyte Implantation for a Trochlear Defect

Matrix-associated autologous chondrocyte implantation (MACI) is a 2-step technique designed to treat symptomatic full-thickness articular cartilage defects of the knee. In this technique article, MACI (autologous cultured chondrocytes on porcine collagen membrane) is used to treat a femoral trochlear defect of the knee. Treating a defect with this technique leads to improved clinical outcomes by restoring the native chondral surface architecture and biomechanics of the knee. In addition, it has the potential to prevent or delay further progressive degeneration of the joint. It is a 2-stage procedure consisting of an initial arthroscopic cartilage biopsy, followed by 4 to 6 weeks of in vitro chondrocyte expansion and, finally, re-implantation. We recommend performing the MACI procedure arthroscopically for the second stage to treat a femoral trochlear defect. During the second surgical procedure, we examine and prepare the recipient site, followed by graft introduction in an all-arthroscopic manner via dry scoping, secured by a thin layer of fibrin glue.

Combination of a human articular cartilage-derived extracellular matrix scaffold and microfracture techniques for cartilage regeneration: A proof of concept in a sheep model

BackgroundThe utilization of decellularized extracellular matrix has gained considerable attention across numerous areas in regenerative research. Of particular interest is the human articular cartilage-derived extracellular matrix (hACECM), which presents as a promising facilitator for cartilage regeneration. Concurrently, the microfracture (MF) ​technique, a well-established marrow stimulation method, has proven efficacious in the repair of cartilage defects. However, as of the current literature review, no investigations have explored the potential of a combined application of hACECM and the microfracture technique in the repair of cartilage defects within a sheep model. HypothesisThe combination of hACECM scaffold and microfracture will result in improved repair of full-thickness femoral condyle articular cartilage defects compared to the use of either technique alone. Study designControlled laboratory study. MethodsFull-thickness femoral condyle articular cartilage defect (diameter, 7.0 ​mm; debrided down to the subchondral bone plate) were created in the weight-bearing area of the femoral medial and lateral condyles (n ​= ​24). All of defected sheep were randomly divided into four groups: control, microfracture, hACECM scaffold, and hACECM scaffold ​+ ​microfracture. After 3, 6 and 12 months, the chondral repair was assessed for standardized (semi-) quantitative macroscopic, imaging, histological, immunohistochemical, mechanics, and biochemical analyses in each group. ResultAt 3, 6 and 12 months after implantation, the gross view and pathological staining of regenerative tissues were better in the hACECM scaffold and hACECM scaffold ​+ ​microfracture groups than in the microfracture and control groups; Micro-CT result showed that the parameters about the calcified layer of cartilage and subchondral bone were better in the hACECM scaffold and hACECM scaffold ​+ ​microfracture groups than the others, and excessive subchondral bone proliferation in the microfracture group. The results demonstrate that human cartilage extracellular matrix scaffold alone is an efficient, safe and simple way to repair cartilage defects. ConclusionhACECM scaffolds combined with/without microfracture facilitate chondral defect repair. The translational potential of this articlePreclinical large animal models represent an important adjunct and surrogate for studies on articular cartilage repair, while the sheep stifle joint reflects many key features of the human knee and are therefore optimal experimental model for future clinical application in human. In this study, we developed a human articular cartilage-derived extracellular matrix scaffold and to verify the viability of its use in sheep animal models. Clinical studies are warranted to further quantify the effects of hACECM scaffolds in similar settings.

Tissue adhesive, ROS scavenging and injectable PRP-based 'plasticine' for promoting cartilage repair.

Platelet-rich plasma (PRP) that has various growth factors has been used clinically in cartilage repair. However, the short residence time and release time at the injury site limit its therapeutic effect. The present study fabricated a granular hydrogel that was assembled from gelatin microspheres and tannic acid through their abundant hydrogen bonding. Gelatin microspheres with the gelatin concentration of 10 wt% and the diameter distribution of 1-10 μm were used to assemble by tannic acid to form the granular hydrogel, which exhibited elasticity under low shear strain, but flowability under higher shear strain. The viscosity decreased with the increase in shear rate. Meanwhile, the granular hydrogel exhibited self-healing feature during rheology test. Thus, granular hydrogel carrying PRP not only exhibited well-performed injectability but also performed like a 'plasticine' that possessed good plasticity. The granular hydrogel showed tissue adhesion ability and reactive oxygen species scavenging ability. Granular hydrogel carrying PRP transplanted to full-thickness articular cartilage defects could integrate well with native cartilage, resulting in newly formed cartilage articular fully filled in defects and well-integrated with the native cartilage and subchondral bone. The unique features of the present granular hydrogel, including injectability, plasticity, porous structure, tissue adhesion and reactive oxygen species scavenging provided an ideal PRP carrier toward cartilage tissue engineering.

Construction of ultrasonically treated collagen/silk fibroin composite scaffolds to induce cartilage regeneration

A novel tissue-specific functional tissue engineering scaffold for cartilage repair should have a three-dimensional structure, good biosafety and biological activity, and should be able to promote cartilage tissue regeneration. This study aimed to determine the effect of ultrasound-treated collagen/silk fibroin (Col/SF) composite scaffolds with good mechanical properties and high biological activity on cartilage repair. The characteristics of the scaffolds with different Col/SF ratios (7:3, 8:2, and 9:1) were determined by scanning electron microscopy, Fourier-transform infrared spectroscopy, and porosity, water absorption, and compression tests. In vitro evaluations revealed the biocompatibility of the Col/SF scaffolds. Results suggested that the optimal ratio of Col/SF composite scaffolds was 7:3. The Col/SF scaffolds induced adipose-derived stem cells to undergo chondrogenic differentiation under chondrogenic culture conditions. The efficiency of Col/SF scaffolds for cartilage regeneration applications was further evaluated using an in vivo model of full-thickness articular cartilage defects in New Zealand rabbits. The Col/SF scaffolds effectively promoted osteochondral regeneration as evidenced by macroscopic, histological, and immunohistochemical evaluation. The study demonstrates that ultrasound-treated Col/SF scaffolds show great potential for repairing cartilage defects.

Repair of full-thickness articular cartilage defects with a 3DP-anchored three-phase complex

IntroductionTo repair cartilage defect as well as the calcified cartilage layer (CCL) and bone tissue, there is need to fabricate a three-phase complex that mimics the natural cartilage tissue. Materials and methodsSF/Col-Ⅱ/HA scaffolds were constructed by low-temperature 3D printing, and to prepare a three-phase complex. The microstructure were showed using a SEM image analysis program. To observe collagen and glycosaminoglycan expression and analyze morphometric parameters, HE staining was performed to reveal new cartilage. Immunohistochemical were performed to investigate the collagen content and defect repair status in the new cartilage group in vitro and vivo. ResultsPhysical and biochemical properties and biocompatibility of three-phase complex met the requirements of constructing tissue-engineered cartilage. The OD values increased gradually at different time points. With increasing culture time, the OD values showed an upward trend. The HE and immunohistochemical staining results showed that new cartilage had formed at the defect and new cartilage formation occurred during in vivo repair. Conclusion3DP-anchored three-phase complexes have good physical and biochemical properties and biocompatibility and thus represent an alternative cartilage tissue engineering material.

Construction of 3D-Bioprinted cartilage-mimicking substitute based on photo-crosslinkable Wharton's jelly bioinks for full-thickness articular cartilage defect repair.

Three-dimensional (3D) bioprinted cartilage-mimicking substitutes for full-thickness articular cartilage defect repair have emerged as alternatives to in situ defect repair models. However, there has been very limited breakthrough in cartilage regeneration based on 3D bioprinting owing to the lack of ideal bioinks with printability, biocompatibility, bioactivity, and suitable physicochemical properties. In contrast to animal-derived natural polymers or acellular matrices, human-derived Wharton's jelly is biocompatible and hypoimmunogenic with an abundant source. Although acellular Wharton's jelly can mimic the chondrogenic microenvironment, it remains challenging to prepare both printable and biologically active bioinks from this material. Here, we firstly prepared methacryloyl-modified acellular Wharton's jelly (AWJMA) using a previously established photo-crosslinking strategy. Subsequently, we combined methacryloyl-modified gelatin with AWJMA to obtain a hybrid hydrogel that exhibited both physicochemical properties and biological activities that were suitable for 3D bioprinting. Moreover, bone marrow mesenchymal stem cell-loaded 3D-bioprinted cartilage-mimicking substitutes had superior advantages for the survival, proliferation, spreading, and chondrogenic differentiation of bone marrow mesenchymal stem cells, which enabled satisfactory repair of a model of full-thickness articular cartilage defect in the rabbit knee joint. The current study provides a novel strategy based on 3D bioprinting of cartilage-mimicking substitutes for full-thickness articular cartilage defect repair.

Demonstration of the Medial Subvastus Knee Exposure for MACI Implantation

Background: There are several techniques for knee exposure in treating chondral defects with restorative procedures. The medial subvastus knee exposure is often overlooked when choosing the surgical approach. When properly performed, the medial subvastus approach can allow for the treatment of a wide range of pathology while preserving the extensor mechanism. Indications: We present a case of an active 40-year-old man with persistent left knee pain noted to have a full-thickness medial femoral condylar articular cartilage defect in an otherwise healthy appearing knee. Technique Description: The rationale and considerations for the medial subvastus knee exposure in treating a chondral defect with an autologous chondrocyte implant are discussed. Careful consideration of the approach, intra-articular exposure, and closure are emphasized to achieve optimal outcomes. Results: At 18 months postoperative, the patient reported no knee pain with improvements made in Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm, and International Knee Documentation Committee (IKDC) scores. These results are consistent with our institutions larger cohort of 26 patients undergoing matrix-induced autologous chondrocyte implantation (MACI) using the subvastus approach. These improvements in patient-reported outcomes are maintained at 2 years postoperative and are consistent with other published outcomes of the MACI procedure. Discussion/Conclusion: Excellent results in addressing chondral pathology about the knee can be achieved by selecting the appropriate surgical access. The subvastus approach has several advantages such as preserving the quadriceps mechanism, improving postoperative quadriceps muscle strength, conservation of the patellar genicular blood supply and possibly reducing postoperative pain that can result in a faster rehabilitation. When performed systematically and carefully, complete exposure of the knee can be achieved to facilitate a wide variety of surgical interventions. In patients undergoing cartilage restoration procedures, the medial subvastus approach should be considered in the surgeon’s armamentarium. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Exploring the Mechanism of Microfracture in the Treatment of Porcine Full-Thickness Cartilage Defect

Background: Microfracture has the most extensive clinical application because of its advantages of a single operation, unified process, and low operation cost. Because research on the repair mechanism of microfractures in the treatment of cartilage defects is not in-depth, this study aimed to elucidate the mechanism. Purpose: To identify the characteristic cell subsets at different repair stages after microfracture, systematically analyze the repair process of the defect area after microfracture, and investigate the mechanism of fibrocartilage repair. Study Design: Descriptive laboratory study. Methods: Full-thickness articular cartilage defects and microfractures was established in the right knee of Bama miniature pigs. Single-cell transcriptional assays were used to identify the characteristics of cells isolated from healthy articular cartilage and regenerated tissues. Results: Microfractures induced mature fibrous repair in the full-thickness cartilage defect six months after surgery, while early stages of repair occurred within six weeks. Based on single-cell sequencing results, eight subsets and specific marker genes were identified. Two processes may occur after microfracture: normal hyaline cartilage regeneration and abnormal fibrocartilage repair. Regulatory chondrocytes, proliferative chondrocytes and cartilage progenitor cells (CPCs) may play important roles in the normal regeneration process. During abnormal repair, CPCs and skeletal stem cells may have different functions, and macrophages and endothelial cells may play important regulatory roles in the formation of fibrochondrocytes. Conclusions: Using single-cell transcriptome sequencing, this study investigated the tissue regeneration process and identified key cell subsets after microfracture. Clinical Relevance: These results provide future targets for optimizing the repair effect of microfracture.

Direct Reprogramming of Mouse Subchondral Bone Osteoblasts into Chondrocyte-like Cells.

Treatment of full-thickness articular cartilage defects with exposure of subchondral bone often seen in osteoarthritic conditions has long been a great challenge, especially with a focus on the feasibility of in situ cartilage regeneration through minimally invasive procedures. Osteoblasts that situate in the subchondral bone plate may be considered a potentially vital endogenous source of cells for cartilage resurfacing through direct reprogramming into chondrocytes. Microarray-based gene expression profiles were generated to compare tissue-specific transcripts between subchondral bone and cartilage of mice and to assess age-dependent differences of chondrocytes as well. On osteoblast cell lines established from mouse proximal tibial subchondral bone, sequential screening by co-transduction of transcription factor (TF) genes that distinguish chondrocytes from osteoblasts reveals a shortlist of potential reprogramming factors exhibiting combined effects in inducing chondrogenesis of subchondral bone osteoblasts. A further combinatorial approach unexpectedly identified two 3-TF combinations containing Sox9 and Sox5 that exhibit differences in reprogramming propensity with the third TF c-Myc or Plagl1, which appeared to direct the converted chondrocytes toward either a superficial or a deeper zone phenotype. Thus, our approach demonstrates the possibility of converting osteoblasts into two major chondrocyte subpopulations with two combinations of three genes (Sox9, Sox5, and c-Myc or Plagl1). The findings may have important implications for developing novel in situ regeneration strategies for the reconstruction of full-thickness cartilage defects.

Effect of platelet-rich plasma scaffolding combined with osteochondral autograft transfer for full-thickness articular cartilage defects of the femoral condyle

We aimed to investigate the local application methods of platelet-rich plasma (PRP) and the effect and safety of PRP scaffolding combined with osteochondral autograft transfer (OAT) in the treatment of full-thickness articular cartilage defects of the femoral condyle. Patients with cartilage defects of the femoral condyle were treated with OAT combined with PRP scaffolding between July 2017 and December 2020. Preoperative magnetic resonance imaging (MRI) and computed tomography were utilized to assess the size, location, and severity of the osteochondral defects. X-ray and MRI images of the knee were obtained at the final follow-up to assess the osseointegration and integrity of the implanted articular cartilage. Osteoarthritic changes in the knee joint were evaluated using the Kellgren–Lawrence grading system. Clinical status was assessed using the visual analog scale (VAS), International Knee Documentation Committee (IKDC), and Lysholm scores before the treatment and at the final follow-up. Complications and patient satisfaction were recorded to assess the safety of this combination therapy. Twenty-one patients were recruited, with a mean follow-up duration of 18.23 ± 6.84 months. The mean lesion size was 2.3 ± 0.59 cm2. The mean platelet concentration in PRP at baseline was 6.27 ± 0.63 times greater than that in the peripheral blood. The VAS, IKDC, and Lysholm scores had improved significantly at the final follow-up (P < 0.001). No serious complications such as joint infection, deep venous thrombosis, or hematoma were observed. Eighteen patients (85.72%) were satisfied with their knee function and quality of life at the final follow-up. Three patients (14.28%) complained of mild anterior knee pain, which was relieved by oral administration of nonsteroidal anti-inflammatory drugs. MRI examinations of all patients showed bony consolidation and the defect surface was covered with cartilage-like tissue. X-ray evaluations indicated that osteoarthritis in two knees (9.5%) had progressed from grade 1 to grade 2 at the final follow-up. The preliminary results showed that OAT combined with PRP may be a safe and effective technique for the treatment of full-thickness articular cartilage defects in the knee.

Оценка синовита голеностопного сустава при диабетической нейроостеоартропатии в зависимости от воспалительной фазы хронического остеомиелита

Diabetic neuroosteoarthropathy complicated by osteomyelitis is one of the severe conditions of the ankle joint in patients with diabetes. The role of the synovium in the pathogenesis of this disease remains poorly understood. Purpose To identify structural changes in the synovium of the Charcot ankle depending on the inflammatory phase of chronic osteomyelitis. Material and methods The synovium and osteochondral fragments of the ankle were studied in 33 patients. Paraffin sections stained according to the three-color Masson method, hematoxylin and eosin, and semi-thin sections stained with methylene blue and basic fuchsin were studied using an AxioScope. A1 microscope with an AxioCam digital camera (Carl Zeiss MicroImaging GmbH, Germany) and Zenblue software (Carl Zeiss MicroImaging GmbH, Germany). The phase of the inflammatory process of chronic osteomyelitis was assessed according to the HOES of Tiemann et al (2014) and synovitis according to Krenn et al (2006). Results Full-thickness articular cartilage defects, synovial pannus, foci of osteonecrosis in the subchondral zone, bone microsequesters, osteoclastic resorption of the subchondral bone plate, replacement of bone marrow structures with granulation tissue, the severity which depended on the inflammatory stage of chronic osteomyelitis, were recorded in the process of studying osteochondral fragments. In 82 % of patients, the inflammatory phase of chronic osteomyelitis was characterized as active and subacute. In all the cases, hyperplasia, hypervascularization and hyperemia of the synovium with the presence of bone and cartilage fragments were observed, as well as inflammatory infiltrate, synovial pannus invading the articular cartilage. The vessels featured a pronounced narrowing of the lumens or their complete closure. The severity of synovitis correlated positively with the inflammatory phase of chronic osteomyelitis; Spearman's correlation coefficient of 0.76 indicated high relationship. Conclusions In diabetic osteoarthropathy of the ankle joint complicated by chronic osteomyelitis, the irreversible structural changes revealed in the synovium contribute to the formation of synovial pannus and the progression of destruction of the articular cartilage and subchondral bone. The severity of synovitis positively correlates with the inflammatory phase of chronic osteomyelitis.

Functionalized Hydrogels for Articular Cartilage Tissue Engineering

Articular cartilage (AC) is an avascular and flexible connective tissue located on the bone surface in the diarthrodial joints. AC defects are common in the knees of young and physically active individuals. Because of the lack of suitable tissue-engineered artificial matrices, current therapies for AC defects, especially full-thickness AC defects and osteochondral interfaces, fail to replace or regenerate damaged cartilage adequately. With rapid research and development advancements in AC tissue engineering (ACTE), functionalized hydrogels have emerged as promising cartilage matrix substitutes because of their favorable biomechanical properties, water content, swelling ability, cytocompatibility, biodegradability, and lubricating behaviors. They can be rationally designed and conveniently tuned to simulate the extracellular matrix of cartilage. This article briefly introduces the composition, structure, and function of AC and its defects, followed by a comprehensive review of the exquisite (bio)design and (bio)fabrication of functionalized hydrogels for AC repair. Finally, we summarize the challenges encountered in functionalized hydrogel-based strategies for ACTE both in vivo and in vitro and the future directions for clinical translation.

Induction of chondrogenesis with a RANKL-binding peptide, WP9QY, in vitro and in vivo in a rabbit model

WP9QY (W9) is a receptor activator of nuclear factor-κB ligand (RANKL)-binding peptide that inhibits osteoclastogenesis by blunting the RANKL-RANK interaction, and also increases osteoblastogenesis via RANKL reverse signaling. W9 has dual effects on osteoclasts and osteoblasts; however, it is unknown whether the peptide has an effect on chondrocytes. Here, we report that W9 induces proliferation and differentiation of chondrocytes in vitro and repairs full-thickness articular cartilage defects in vivo. W9 stimulated chondrocyte differentiation in a two-dimensional (2D) culture of human mesenchymal stem cells (hMSCs), and transforming growth factor β3 (TGF-β3) showed synergistic effects with W9 on chondrogenesis. W9 enlarged the size of 3D pellet cultures of hMSCs and produced chondrocyte-specific matrices, especially in combined treatment with TGF-β3. The peptide also stimulated proliferation of hMSCs with induction of expression of chondrogenesis-related genes. Several RANKL inhibitors had no effect on chondrocytic differentiation. RANKL-knockdown experiments showed that W9 did not induce chondrogenesis through RANKL, but did induce osteoblastogenesis through RANKL. Intraarticular injection of W9 resulted in significant repair of full-thickness articular cartilage defects in rabbits. Taken together, these results suggest that W9 ameliorates the articular cartilage defects by increasing the volume of cartilaginous matrices with accompanying induction of proliferation and differentiation of chondrocytes via mechanisms independent of RANKL inhibition and RANKL reverse signaling. Since no pharmaceuticals are clinically available for treatment of cartilage damage such as osteoarthritis, our findings demonstrate the potential of W9 to address the unmet medical needs.

Generation of hybrid tissue engineered construct through embedding autologous chondrocyte loaded platelet rich plasma/alginate based hydrogel in porous scaffold for cartilage regeneration

Over the past decades, various attempts have been made to develop suitable tissue-engineered constructs to repair or regenerate the damaged or diseased articular cartilage. In the present study, we embedded Platelet rich plasma (PRP)/Sodium Alginate (SA) based hydrogel in porous 3D scaffold of chitosan (CH)/chondroitin sulfate (CS)/silk fibroin (SF) to develop hybrid scaffold for cartilage tissue construct generation with abilities to support shape recovery potential, facilitate uniform cells distribution and mimic gel like cartilage tissue extracellular matrix.The developed hybrid matrix shows suitable pore size (55–261 μm), porosity (77 ± 4.3%) and compressive strength (0.13 ± 0.04 MPa) for cartilage tissue construct generation and its applications. The developed SA/PRP-based cartilage construct exhibits higher metabolic activity, glycosaminoglycan deposition, expression of collagen type II, and aggrecan in comparison to SA based cell-scaffold construct. In-vivo animal study was also performed to investigate the biocompatibility and cartilage tissue regeneration potential of the developed construct. The obtained gross analysis of knee sample, micro-computed tomography, and histological analysis suggest that implanted tissue construct possess the superior potential to regenerate hyaline cartilage defect of thickness around 1.10 ± 0.36 mm and integrate with surrounding tissue at the defect site. Thus, the proposed strategy for the development of cartilage tissue constructs might be beneficial for the repair of full-thickness knee articular cartilage defects.

Patellar MACI With Tibial Tubercle Osteotomy

Background: Chondral pathology is frequently encountered during knee arthroscopies with a prevalence rate of 63% to 66%. Prior studies have demonstrated that unaddressed or excised fragments result in poor knee function and arthritis. As a result, chondral-related procedures have increased in popularity, and now more than 200,000 procedures are performed annually. Indications: We present a case of an active 32-year-old woman, prior collegiate basketball player, with persistent left knee pain noted to have a full-thickness patellar articular cartilage defect and maltracking. Technique: A patellar autologous matrix-induced chondrocyte is implanted with a concomitant tibial tubercle osteotomy (TTO) and lateral retinacular lengthening. Results: At 9 weeks, the patient had no knee pain with full range of motion symmetric to the contralateral side while slowly progressing with quadriceps strengthening. Discussion/Conclusion: Successful outcomes addressing large patellar chondral defects and maltracking can be achieved with matrix autologous chondrocyte implantation and concomitant TTO with lateral retinacular lengthening.

Zonal-Layered Chondrocyte Sheets for Repairment of Full-Thickness Articular Cartilage Defect: A Mini-Pig Model

The cell sheet technique is a promising approach for tissue engineering, and the present study is aimed to determine a better configuration of cell sheets for cartilage repair. For stratified chondrocyte sheets (S-CS), articular chondrocytes isolated from superficial, middle, and deep zones were stacked accordingly. Heterogeneous chondrocyte sheets (H-CS) were obtained by mixing zonal chondrocytes. The expressions of chondrocytes, cytokine markers, and glycosaminoglycan (GAG) production were assessed in an in vitro assay. The curative effect was investigated in an in vivo porcine osteochondral defect model. The S-CS showed a higher cell viability, proliferation rate, expression of chondrogenic markers, secretion of tissue inhibitor of metalloproteinase, and GAG production level than the H-CS group. The expressions of ECM destruction enzyme and proinflammatory cytokines were lower in the S-CS group. In the mini-pigs articular cartilage defect model, the S-CS group had a higher International Cartilage Repair Society (ICRS) macroscopic score and displayed a zonal structure that more closely resembled the native cartilage than those implanted with the H-CS. Our study demonstrated that the application of the S-CS increased the hyaline cartilage formation and improved the surgical outcome of chondrocyte implication, offering a better tissue engineering strategy for treating articular cartilage defects.

Rat perichondrium transplanted to articular cartilage defects forms articular-like, hyaline cartilage.

Perichondrium autotransplants have been used to reconstruct articular surfaces destroyed by infection or trauma. However, the role of the transplanted perichondrium in the healing of resurfaced joints has not been investigated. Perichondrial and periosteal tissues were harvested from rats hemizygous for a ubiquitously expressed enhanced green fluorescent protein (EGFP) transgene and transplanted into full-thickness articular cartilage defects at the trochlear groove of distal femur in wild-type littermates. As an additional control, cartilage defects were left without a transplant (no transplant control). Distal femurs were collected 3, 14, 56, 112days after surgery. Tracing of transplanted cells showed that both perichondrium and periosteum transplant-derived cells made up the large majority of the cells in the regenerated joint surfaces. Perichondrium transplants contained SOX9 positive cells and with time differentiated into a hyaline cartilage that expanded and filled out the defects with Col2a1-positive and Col1a1-negative chondrocytes and a matrix rich in proteoglycans. At later timepoints the cartilaginous perichondrium transplants were actively remodeled into bone at the transplant-bone interface and at post-surgery day 112 EGFP-positive perichondrium cells at the articular surface were positive for Prg4. Periosteum transplants initially lacked SOX9 expression and despite a transient increase in SOX9 expression and chondrogenic differentiation, remained Col1a1 positive, and were continuously thinning as periosteum-derived cells were incorporated into the subchondral compartment. Perichondrium and periosteum transplanted to articular cartilage defects did not just stimulate regeneration but were themselves transformed into cartilaginous articular surfaces. Perichondrium transplants developed into an articular-like, hyaline cartilage, whereas periosteum transplants appeared to produce a less resilient fibro-cartilage.

Good healing potential of patellar chondral defects after all-arthroscopic autologous chondrocyte implantation with spheroids: a second-look arthroscopic assessment.

To report second-look arthroscopic assessment after all-arthroscopic autologous chondrocyte implantation (ACI) for articular cartilage defects at the patella. A second-look arthroscopy after all-arthroscopic ACI using chondrospheres® (ACT3D) was performed in 30 patients with 30 full-thickness retropatellar cartilage defects. The mean time from ACI to second-look arthroscopy was 14.9 ± 16.3 (6-71) months. The quality of cartilage regeneration was evaluated by the International Cartilage-Repair Score (ICRS)-Cartilage Repair Assessment (CRA). Eleven lesions (36.7%) were classified as CRA grade I (normal) and 19 lesions (63.3%) as grade II (nearly normal). Concerning the degree of defect repair, 25 lesions (83.3%) were repaired up to the height of the surrounding articular retropatellar cartilage. Five lesions (16.7%) showed 75% repair of defect depth. The border zone was completely integrated into the surrounding articular cartilage shoulder in 28 lesions (93.3%) and demarcated within 1mm in 2 lesions (6.7%). Macroscopically and by probing, 12 lesions (40%) had intact smooth surface, 17 lesions (56.7%) had fibrillated surface and 1 lesion (3.3%) had small, scattered fissures. A negative correlation was found between the overall repair assessment score and the defect size (r2 = -0.430, p = 0.046) and between integration into border zone and defect size (r2 = -0.340, p = 0.045). A positive correlation was found between macroscopic appearance and age (r2 = + 0.384, p = 0.036). All-arthroscopic ACI using chondrospheres® (ACT3D) for full-thickness retropatellar articular cartilage defects proved to be reproducible and reliable. The advantage of the procedure is that it is minimal invasive. Arthroscopic second-look demonstrated a high grade of normal or nearly normal cartilage regeneration. Although statistically significant differences were not observed, larger defect size and younger age may compromise the result of overall repair. III.

Rat perichondrium transplanted to articular cartilage defects forms articular-like, hyaline cartilage

Abstract Objective Perichondrium autotransplants have been used to reconstruct articular surfaces destroyed by infection or trauma. However, the role of the transplanted perichondrium in the healing of resurfaced joints has not been investigated. Design Perichondrial and periosteal tissues were harvested from rats hemizygous for a ubiquitously expressed enhanced green fluorescent protein (EGFP) transgene and transplanted into full-thickness articular cartilage defects at the trochlear groove of distal femur in wild-type littermates. As an additional control, cartilage defects were left without a transplant (no transplant control). Distal femurs were collected 3, 14, 56, 112 days after surgery. Results Tracing of transplanted cells showed that both perichondrium and periosteum transplant-derived cells made up the large majority of the cells in the regenerated joint surfaces. Perichondrium transplants contained SOX9 positive cells and with time differentiated into a hyaline cartilage that expanded and filled out the defects with Col2a1-positive and Col1a1-negative chondrocytes and a matrix rich in proteoglycans. At later timepoints the cartilaginous perichondrium transplants were actively remodeled into bone at the transplant-bone interface and at post-surgery day 112 EGFP-positive perichondrium cells at the articular surface were positive for Prg4. Periosteum transplants initially lacked SOX9 expression and despite a transient increase in SOX9 expression and chondrogenic differentiation, remained Col1a1 positive, and were continuously thinning as periosteum-derived cells were incorporated into the subchondral compartment. Conclusions Perichondrium and periosteum transplanted to articular cartilage defects did not just stimulate regeneration but were themselves transformed into cartilaginous articular surfaces. Perichondrium transplants developed into an articular-like, hyaline cartilage, whereas periosteum transplants appeared to produce a less resilient fibro-cartilage.