Osteochondral Defects In Knee Research Articles

Mid-term results of impaction bone grafting and autologous matrix-induced chondrogenesis for knee osteochondral defects

Mid-term results of impaction bone grafting and autologous matrix-induced chondrogenesis for knee osteochondral defects

Does AMIC® provide improvements at least two years after surgery for knee osteochondral lesions? A multicentre retrospective study of 101 patients

BackgroundOsteochondral defects of the knee due to trauma or osteochondritis are associated with osteoarthritis in the medium term. Defects 2 to 8cm2 in size can be managed by autologous matrix-induced chondrogenesis (AMIC®), in which sub-chondral micro-fractures are created within the lesion and the defect is then covered by a matrix of type I and type III collagen to induce de novo cartilage formation. Although promising outcomes have been observed in small single-centre cohorts, the medium-term clinical and radiological effectiveness of AMIC® remains to be demonstrated in larger populations. The objective of this study was to evaluate outcomes of patients at least 2 years after AMIC® for knee osteochondral defects. HypothesisAMIC® is associated with clinical and radiological improvements after at least 2 years. Material and methodThis multicentre (16 centres), multisurgeon (18 senior orthopaedic surgeons), retrospective study included consecutive patients who underwent AMIC® with Chondro-Gide® membrane implantation between September 2011 and January 2020. The 36-item Short Form quality-of-life (SF-36) score, Knee Injury and Osteoarthritis Outcome Score (KOOS), and International Knee Documentation Committee (IKDC) score were determined before the procedure and during follow-up. The Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score was assessed by magnetic resonance imaging 2 years after the procedure. ResultsIn total, 101 patients aged 12 to 60 years were included. Mean follow-up was 30 months. Mean defect size was 3.44cm2 (range, 2–8cm2). Significant improvements were documented in the SF-36 score, KOOS, and IKDC score. The mean MOCART score at 2 years was 75% (range, 20–100). DiscussionThe AMIC® procedure was associated with significant improvements at 2.5 years in patients treated for knee osteochondral defects measuring 2 to 8cm2. This method seems to provide similar outcomes to those of other available methods with the advantages of single-step surgery and elimination of osteochondral graft donor-site complications. Level of evidenceIV, retrospective observational cohort study.

Satisfactory patient-reported outcomes in patients treated with impaction bone grafting and autologous matrix-induced chondrogenesis for osteochondral knee defects.

Osteochondral knee defects usually affect young, active patients and may alter knee biomechanics and progressively lead to joint degeneration. Various treatment options exist with autologous, impaction bone grafting in combination with autologous matrix-induced chondrogenesis (BG-AMIC) being a less-expensive, one-step, promising option. The purpose of this study is to evaluate the clinical and radiological mid-term outcomes of large osteochondral lesions treated with BG-AMIC, identify a possible correlation between the two and report postoperative complications and reoperation rate. A retrospective analysis of 25 patients treated with the BG-AMIC technique for knee osteochondral lesions was performed. Patients were assessed using the following PROMs: the IKDC, the KOOS and the Lysholm score, the Tegner activity scale and a patient acceptable symptom state (PASS). TheEQ-5D-5L score was used to assess health-related quality of life. Radiological assessment was performed using the MOCART 2.0 score on a 3T MRI. At a mean of 3.8 (± 0.8)-year follow-up, all functional scores increased significantly (p < 0.005) when compared to the preoperative baseline. IKDC increased from 44.5 (± 15.9) to 81.4 (± 14.7), KOOS from 41.5 (± 16.1) to 91.6 (± 11.6) and Lysholm from 54.4 (± 23) to 95.2 (± 5.5) (p < 0.005). The EQ-5D-5L score also revealed a significant improvement [59.9 (± 25) to 93.4 (± 10.2), p < 0.005]. Mean Tegner score reached pre-injury levels. The PASS was positive in 100% of patients. The minimum clinically important difference was reached in all PROMs except for the KOOS Sports subscale. There were no re-operations. Morphological evaluation of the repair tissue using the MOCART 2.0 score revealed a mean total score of 52.8 (± 30.5). A statistically significant, positive correlation was found between the MOCART 2.0 score and the IKDC score, the KOOS ADL subscale and the EQ-5D-5L (p < 0.05). BG-AMIC is a safe and reliable option for treating deep, knee osteochondral lesions, providing a statistically significant and clinically important improvement in patient-reported outcomes. No complications were noticed, and no re-operations were performed after the procedure. A moderate positive correlation between the MOCART 2.0 score and the IKDC, KOOS ADL and EQ-5D-5L was noticed. However, this correlation is not necessarily clinically relevant, and excellent clinical results can be expected even in patients with low MOCART scores. III.

Development of cartilage tissue using a stirred bioreactor and human iPSC-derived limb bud mesenchymal cells

Production of cartilaginous particles for regenerative medicine requires a large supply of chondrocytes and development of suitable production techniques. Previously, we successfully produced human induced pluripotent stem cell (hiPSC)-derived limb bud mesenchymal cells (ExpLBM cells) with a high chondrogenic differentiation potential that stably proliferate. It may be possible to use these cells in combination with a stirred bioreactor to develop a tissue-engineered cell culture technology with potential for scale-up to facilitate production of large amounts of cartilaginous particles. ExpLBM cells derived from 414C2 and Ff-I 14s04 (human leukocyte antigen homozygous) hiPSCs were seeded into a stirred bioreactor containing cartilage induction medium. To characterize the cartilaginous particles produced, we performed real-time quantitative reverse transcription-polymerase chain reaction and histological analyses. Additionally, we transplanted the cartilage tissue into osteochondral defects of immunocompromised rats to assess its functionality, and evaluated engraftment of the grafted tissue. We successfully produced large amounts of cartilaginous particles via cartilage induction culture in a stirred bioreactor. This tissue exhibited significantly increased expression levels of type II collagen (COL2), aggrecan (ACAN), and SRY-box transcription factor 9 (SOX9), as well as positive Safranin O and Toluidine blue staining, indicating that it possesses characteristics of hyaline cartilage. Furthermore, engrafted tissues in osteochondral knee defects of immunodeficient rats were positively stained for human vimentin, COL2, and ACAN as well as with Safranin O. In this study, we successfully generated large amounts of hiPSC-derived cartilaginous particles using a combination of tissue engineering techniques. This method is promising as a cartilage regeneration technology with potential for scale-up.

Decellularized allogeneic cartilage paste with human costal cartilage and crosslinked hyaluronic acid-carboxymethyl cellulose carrier augments microfracture for improved articular cartilage repair

Articular cartilage lacks natural healing abilities and necessitates surgical treatments for injuries. While microfracture (MF) is a primary surgical approach, it often results in the formation of unstable fibrocartilage. Delivering hyaline cartilage directly to defects poses challenges due to the limited availability of autologous cartilage and difficulties associated with allogeneic cartilage delivery. We developed a decellularized allogeneic cartilage paste (DACP) using human costal cartilage mixed with a crosslinked hyaluronic acid (HA)-carboxymethyl cellulose (CMC) carrier. The decellularized allogeneic cartilage preserved the extracellular matrix and the nanostructure of native hyaline cartilage. The crosslinked HA-CMC carrier provided shape retention and moldability. In vitro studies confirmed that DACP did not cause cytotoxicity and promoted migration, proliferation, and chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells. After 6 months of implantation in rabbit knee osteochondral defects, DACP combined with MF outperformed MF alone, demonstrating improved gait performance, defect filling, morphology, extracellular matrix deposition, and biomechanical properties similar to native cartilage. Thus, DACP offers a safe and effective method for articular cartilage repair, representing a promising augmentation to MF. Statement of significanceDirectly delivering hyaline cartilage to repair articular cartilage defects is an ideal treatment. However, current allogeneic cartilage products face delivery challenges. In this study, we developed a decellularized allogeneic cartilage paste (DACP) by mixing human costal cartilage with crosslinked hyaluronic acid (HA)-carboxymethyl cellulose (CMC). DACP preserves extracellular matrix components and nanostructures similar to native cartilage, with HA-CMC ensuring shape retention and moldability. Our study demonstrates improved cartilage repair by combining DACP with microfracture, compared to microfracture alone, in rabbit knee defects over 6 months. This is the first report showing better articular cartilage repair using decellularized allogeneic cartilage with microfracture, without the need for exogenous cells or bioactive substances.

Histomorphological Investigation of Microfracture Location in a Rabbit Osteochondral Defect Model.

Microfracture is the most common treatment for cartilage defects of the knee. In microfracture surgery, holes are randomly drilled into the subchondral bone. The effect of the hole's location on its interaction with the cartilage defect site and its influence on the healing process is currently uncertain. To investigate the effects of different microfracture locations on healing in a rabbit knee osteochondral defect model. Controlled laboratory study. A total of 29 adult New Zealand White rabbits were divided into 5 groups. In the healthy cartilage control group (n = 5), no surgical procedure was performed. Cylindrical full-thickness cartilage defects (5 × 3 mm) were created in the patellar groove of the remaining 24 rabbits. In the defect control group (n = 6), only the defect was created. A microfracture was performed at the 12-o'clock position (group peripheral single; n = 6), centrally (group central; n = 6), and at the 12- and 6-o'clock positions (group peripheral double; n = 6) of the defect. The animals were sacrificed after 8 weeks. Cartilage healing was evaluated by International Cartilage Regeneration & Joint Preservation Society (ICRS) score, modified O'Driscoll score, immunohistochemical analysis (type 1 collagen, type 2 collagen, and aggrecan), and scanning electron microscopy analysis. In group peripheral double, better cartilage healing was observed in all parameters compared with the other groups (P < .05). Group peripheral double had the greatest amount of filling, with 79% of the defect area filled with fibrocartilage repair tissue. Group peripheral single demonstrated filling of 73% of the defect area, group central 56%, and the defect control group 45%. The ICRS score was significantly higher in group peripheral single compared with group central and the defect control group. Type 2 collagen and aggrecan immunoreactivity were significantly stronger in group central than group peripheral single and the defect control group (P < .05). Microfracture performed at the peripheral margin of the defect had better filling characteristics in a rabbit model. This study suggests that interaction of pluripotent cells released from the microfracture site with the intact cartilage may enhance the quality of the repair tissue. The location of microfracture holes in relation to the peripheral border of the osteochondral defect (to the intact cartilage) is important in both the quality and the quantity of the newly formed repair tissue.

Engineering exosomes by three-dimensional porous scaffold culture of human umbilical cord mesenchymal stem cells promote osteochondral repair.

Improving the poor microenvironment in the joint cavity has potential for treating cartilage injury, and mesenchymal stem cell (MSC)-derived exosomes (MSC-Exos), which can modulate cellular behavior, are becoming a new cell-free therapy for cartilage repair. Here, we used acellular cartilage extracellular matrix (ACECM) to prepare 3D scaffolds and 2D substrates by low-temperature deposition modeling (LDM) and tape casting. We aimed to investigate whether MSC-Exos cultured on scaffolds of different dimensions could improve the poor joint cavity microenvironment caused by cartilage injury and to explore the related mechanisms. In vitro experiments showed that exosomes derived from MSCs cultured on three-dimensional (3D) scaffolds (3D-Exos) had increased efficiency. In short-term animal experiments, compared with exosomes derived from MSCs cultured in a two-dimensional (2D) environment (2D-Exos), 3D-Exos had a stronger ability to regulate the joint cavity microenvironment. Long-term animal studies confirmed the therapeutic efficacy of 3D-Exos over 2D-Exos. Thus, 3D-Exos were applied in the rat knee osteochondral defect model after adsorption in the micropores of the scaffold and combined with subsequent articular cavity injections, and they showed a stronger cartilage repair ability. These findings provide a new strategy for repairing articular cartilage damage. Furthermore, miRNA sequencing indicated that the function of 3D-Exos may be associated with high expression of miRNAs. Thus, our study provides valuable insights for the design of 3D-Exos to promote cartilage regeneration.

Autologous Conditioned Plasma and Hyaluronic Acid Injection for Isolated Grade 4 Osteochondral Lesions of the Knee in Young Active Adults.

Objectives: To compare the short-term benefits and results of autologous conditioned plasma (ACP) and hyaluronic acid (HA) injection in osteochondral defects in the knee of young adults. The effectiveness of intra-articular platelet-rich plasma (PRP) injections has been evaluated in osteoarthritis. However, few studies investigated its efficacy in knee osteochondral defects.Methods: This is a retrospective analysis of prospectively collected data. A matched cohort of 30 patients in each group was studied. Group 1 received three HA injections at weekly intervals, and group 2 received three ACP injections at two weekly intervals. We measured Kujala, Lysholm, Oxford, and visual analog scale (VAS) scores at baseline, six, 12, and 36 months to assess function and pain.Results: Most lesions were in the medial femoral condyles in both groups, followed by lateral femoral condyle and patellofemoral regions. In group 1 (HA), the mean pre-injection scores for Kujala, Lysholm, and Oxford improved significantly at six and 12 months. The scores decreased at 36 months, however, they remained significantly better than the baselines (P < 0.05). The pre-injection VAS scores continued to improve significantly from 6.06±0.785 to 3.40±0.912 at 36 weeks. In group 2 (ACP), VAS and the outcome scores showed a consistent and statistically significant improvement from pre-injection to 36 months. Conclusions: Our study confirms the short-term clinical benefits of using ACP for symptomatic osteochondral defects of the knee. Further high-quality comparative studies with longer follow-ups are needed to ascertain whether ACP is beneficial in the long term.

Mimicking osteochondral interface using pre-differentiated BMSCs/fibrous mesh complexes to promote tissue regeneration

The heterogeneous nature of osteochondral tissue requires the construction of implant with biomimetic gradients. Electrospun fibrous meshes with different designs provide the feasibility in arranging such a kind of gradient structure via layer-by-layer stacking. In this study, a kind of triphasic implant was constructed by layering pre-differentiated cell sheets, which were hold by electrospun poly(L-lactide)/gelatin (PLLA/Gel) fibrous meshes containing hyaluronic acid and chondroitin sulfate for the cartilage layer or hydroxyapatite for the bone layer. As for the calcified interlayer, the bone marrow mesenchymal stromal cells (BMSCs) seeded on PLLA/Gel fibrous mesh was pre-differentiated with a mixed osteoinductive/chondroinductive (1:1) medium. With this gradient construct being implanted in rabbit knee osteochondral defect, it was found that both the cartilage and subchondral bone were regenerated effectively with reproduced tidal line structure. The importance of implants with biomimetic gradients for osteochondral defect repair was confirmed, and cell sheets on electrospun fibrous meshes were flexible for gradient structure construction via the layer-by-layer stacking technology. Highlights Composite fibrous meshes with tissue-specific components are electrospun. Confluent BMSCs on fibrous meshes are chondrogenically or osteogenically induced. BMSCs hypertrophy is induced with the mixture of chondroinductive and osteoinductive medium. The pre-differentiated cell/mesh complexes are stacked layer-by-layer to form gradient construct. The gradient construct efficiently promotes osteochondral regeneration in rabbit joint.

Biologic Augmentation for the Operative Treatment of Osteochondral Defects of the Knee: A Systematic Review.

Background:Various surgical treatment options exist for repairing, replacing, or regenerating tissue to fill osteochondral defects. Biologic augmentation has been increasingly studied as an adjunct in the surgical treatment of osteochondral defects of the knee in animal and human models.Purpose/Hypothesis:The purpose of the study was to systematically review use of platelet-rich plasma (PRP) and bone marrow concentrate (BMC) augmentation in the surgical treatment of osteochondral knee defects and to describe the outcomes. It was hypothesized that both PRP and BMC augmentation will result in improved outcomes in osteochondral knee surgery in both animal and human models.Study Design:Systematic review.Methods:PubMed, MEDLINE, and Embase were searched for studies relating to PRP or BMC and treatment of osteochondral defects of the knee, from database inception to February 1, 2020. Included were articles that (1) studied PRP or BMC augmentation; (2) used osteochondral autograft, allograft, or biologic scaffold; and (3) treated osteochondral defects in the knee. Data on use of PRP or BMC, outcomes assessed, and results were recorded for each publication.Results:Of the 541 articles identified initially, 17 were included in the final review. Five articles studied osteochondral grafts in animals, 5 studied biologic scaffolds in animals, and 7 studied scaffolds or allografts in humans; the combined sample size was 202 patients. Of 4 histologic scaffold studies, 3 PRP-augmented scaffold studies identified histologic improvements in regenerated cartilage in animal models, while 1 BMC study demonstrated similar improvement in histologic scores of BMC-augmented scaffolds compared with controls. Three studies associated greater collagen type 2 and glycosaminoglycan content with PRP treatment. Comparative studies found that both augments increase osteogenic proteins, including bone morphogenetic protein–2 and osteoprotegerin. Two of 3 studies on BMC-augmented osteochondral allografts reported no difference in radiographic features postoperatively. Long-term improvement in clinical and radiographic outcomes of PRP-augmented scaffolds was demonstrated in 1 human study.Conclusion:Animal studies suggest that biologics possess potential as adjuncts to surgical treatment of osteochondral knee defects; however, clinical data remain limited.

Chitosan coatings with distinct innate immune bioactivities differentially stimulate angiogenesis, osteogenesis and chondrogenesis in poly-caprolactone scaffolds with controlled interconnecting pore size

This study tested whether osseous integration into poly (ε-caprolactone) (PCL) bioplastic scaffolds with fully-interconnecting 155 ± 8 μm pores is enhanced by an adhesive, non-inflammatory 99% degree of deacetylation (DDA) chitosan coating (99-PCL), or further incorporation of pro-inflammatory 83% DDA chitosan microparticles (83-99-PCL) to accelerate angiogenesis. New Zealand White rabbit osteochondral knee defects were press-fit with PCL, 99-PCL, 83-99-PCL, or allowed to bleed (drill-only). Between day 1 and 6 weeks of repair, drill-only defects repaired by endochondral ossification, with an 8-fold higher bone volume fraction (BVF) versus initial defects, compared to a 2-fold (99-PCL), 1.1-fold (PCL), or 0.4-fold (83-99-PCL) change in BVF. Hematoma innate immune cells swarmed to 83-99-PCL, elicited angiogenesis throughout the pores and induced slight bone resorption. PCL and 99-PCL pores were variably filled with cartilage or avascular mesenchyme near the bone plate, or angiogenic mesenchyme into which repairing trabecular bone infiltrated up to 1 mm deep. More repair cartilage covered the 99-PCL scaffold (65%) than PCL (18%) or 83-99-PCL (0%) (p < 0.005). We report the novel finding that non-inflammatory chitosan coatings promoted cartilage infiltration into and over a bioplastic scaffold, and were compatible with trabecular bone integration. This study also revealed that in vitro osteogenesis assays have limited ability to predict osseous integration into porous scaffolds, because (1) in vivo, woven bone integrates from the leading edge of regenerating trabecular bone and not from mesenchymal cells adhering to scaffold surfaces, and (2) bioactive coatings that attract inflammatory cells induce bone resorption.

The use of a novel deer antler decellularized cartilage-derived matrix scaffold for repair of osteochondral defects

BackgroundThe physiologic regenerative capacity of cartilage is severely limited. Current studies on the repair of osteochondral defects (OCDs) have mainly focused on the regeneration of cartilage tissues. The antler cartilage is a unique regenerative cartilage that has the potential for cartilage repair.MethodsAntler decellularized cartilage-derived matrix scaffolds (adCDMs) were prepared by combining freezing-thawing and enzymatic degradation. Their DNA, glycosaminoglycans (GAGs), and collagen content were then detected. Biosafety and biocompatibility were evaluated by pyrogen detection, hemolysis analysis, cytotoxicity evaluation, and subcutaneous implantation experiments. adCDMs were implanted into rabbit articular cartilage defects for 2 months to evaluate their therapeutic effects.ResultsAdCDMs were observed to be rich in collagen and GAGs and devoid of cells. AdCDMs were also determined to have good biosafety and biocompatibility. Both four- and eight-week treatments of OCDs showed a flat and smooth surface of the healing cartilage at the adCDMs filled site. The international cartilage repair society scores (ICRS) of adCDMs were significantly higher than those of controls (porcine dCDMs and normal saline) (p < 0.05). The repaired tissue in the adCDM group was fibrotic with high collagen, specifically, type II collagen.ConclusionsWe concluded that adCDMs could achieve excellent cartilage regeneration repair in a rabbit knee OCDs model. Our study stresses the importance and benefits of adCDMs in bone formation and overall anatomical reconstitution, and it provides a novel source for developing cartilage-regenerating repair materials.

The partial femoral condyle focal resurfacing (HemiCAP-UniCAP) for treatment of full-thickness cartilage defects, systematic review and meta-analysis

Knee osteochondral defects are a common problem among people, especially young and active patients. So effective joint preserving surgeries is essential to prevent or even delay the onset of osteoarthritis for these group of patients. This study aims to critically appraise and evaluate the evidence for the results and effectiveness of femoral condyle resurfacing (HemiCAP/ UniCAP) in treatment of patients with focal femoral condyle cartilage defect. Using the search terms : HemiCAP, UniCAP, Episurf, focal, femoral, condyle, inlay and resur-facing, we reviewed the PubMed and EMBASE and the Cochrane Database of Systematic Reviews (CDSR) to find any articles published up to March 2020. The short term follow-up of the HemiCAP shows (6.74 %) revision rate. However, 29.13 % loss of follow up let us consider these results with caution especially if the revision rate progressively increased with time to 19.3 % in 5-7 years with no enough evidence for the long term results except the data from the Australian Joint Registry 2018, where the cumulative revision rate was 40.6 % (33.5, 48.4) at ten years. The UniCAP that used for defect more than 4 cm 2 has a high revision rate (53.66 %) which is considered unacceptable revision rate in com-parison to another similar prosthesis such as Uni-Knee Arthroplasty (UKA). The evidence from published studies and our meta- analysis suggests that partial resurfacing of the femoral condyle (HemiCAP) doesn't support its usage as a tool to treat the focal cartilage defect in middle- aged patients. The UniCAP as femoral condyle resurfacing has very high revision rate at 5-7 years (53.66 %) which make us recommend against its usage.

Cell-free decellularized cartilage extracellular matrix scaffolds combined with interleukin 4 promote osteochondral repair through immunomodulatory macrophages: In vitro and in vivo preclinical study

Cartilage regeneration is a complex physiological process. Synovial macrophages play a critical immunomodulatory role in the acute inflammatory response surrounding joint injury. Due to the contrasting differences and heterogeneity of macrophage, the phenotype of macrophages are the key determinants of the healing response after cartilage injury. Biomaterials derived from extracellular matrix have been used for the repair and reconstruction of a variety of tissues by modulating the host macrophage response. However, the immunomodulatory effect of decellularized cartilage extracellular matrix (ECM) on macrophages has not been elucidated. It is necessary to clarify the immunomodulatory properties of decellularized cartilage matrix (DCM) to guide the design of cartilage regeneration materials. Here, we prepared porcine articular cartilage derived DCM and determined the response of mouse bone marrow-derived macrophages (BMDMs) to the pepsin-solubilized DCM (PDCM) in vitro. Macrophages activated by the PDCM could promote bone marrow-derived mesenchymal stem cells (BMSCs) invasion, migration, proliferation, and chondrogenic differentiation. Then, we verified that early optimization of the immunomodulatory effects of the cell-free DCM scaffold using IL-4 in vivo could achieve good cartilage regeneration in a rat knee osteochondral defect model. Therefore, this decellularized cartilage ECM scaffold combined with accurate and active immunomodulatory strategies provides a new approach for the development of cartilage regeneration materials. Statement of significanceThis work reports a decellularized cartilage extracellular matrix (DCM) scaffold combined with an accurate and active immunomodulatory strategy to improve cartilage regeneration. Our findings demonstrated that the pepsin-solubilized DCM (PDCM) activated bone marrow-derived macrophages to polarize to a constructive macrophage phenotype. These polarized macrophages promoted bone marrow-derived mesenchymal stem cell invasion, migration, proliferation, and chondrogenic differentiation. DCM scaffolds combined with early-stage intra-articular injection of IL-4 created a wound-healing microenvironment and improved cartilage regeneration in a rat knee osteochondral defect model.

Enhancement of acellular cartilage matrix scaffold by Wharton's jelly mesenchymal stem cell-derived exosomes to promote osteochondral regeneration

Articular cartilage defect repair is a problem that has long plagued clinicians. Although mesenchymal stem cells (MSCs) have the potential to regenerate articular cartilage, they also have many limitations. Recent studies have found that MSC-derived exosomes (MSC-Exos) play an important role in tissue regeneration. The purpose of this study was to verify whether MSC-Exos can enhance the reparative effect of the acellular cartilage extracellular matrix (ACECM) scaffold and to explore the underlying mechanism. The results of in vitro experiments show that human umbilical cord Wharton's jelly MSC-Exos (hWJMSC-Exos) can promote the migration and proliferation of bone marrow-derived MSCs (BMSCs) and the proliferation of chondrocytes. We also found that hWJMSC-Exos can promote the polarization of macrophages toward the M2 phenotype. The results of a rabbit knee osteochondral defect repair model confirmed that hWJMSC-Exos can enhance the effect of the ACECM scaffold and promote osteochondral regeneration. We demonstrated that hWJMSC-Exos can regulate the microenvironment of the articular cavity using a rat knee joint osteochondral defect model. This effect was mainly manifested in promoting the polarization of macrophages toward the M2 phenotype and inhibiting the inflammatory response, which may be a promoting factor for osteochondral regeneration. In addition, microRNA (miRNA) sequencing confirmed that hWJMSC-Exos contain many miRNAs that can promote the regeneration of hyaline cartilage. We further clarified the role of hWJMSC-Exos in osteochondral regeneration through target gene prediction and pathway enrichment analysis. In summary, this study confirms that hWJMSC-Exos can enhance the effect of the ACECM scaffold and promote osteochondral regeneration.

Characterization of Properties, In Vitro and In Vivo Evaluation of Calcium Phosphate/Amino Acid Cements for Treatment of Osteochondral Defects.

Novel calcium phosphate cements containing a mixture of four amino acids, glycine, proline, hydroxyproline and either lysine or arginine (CAL, CAK) were characterized and used for treatment of artificial osteochondral defects in knee. It was hypothesized that an enhanced concentration of extracellular collagen amino acids (in complex mixture), in connection with bone cement in defect sites, would support the healing of osteochondral defects with successful formation of hyaline cartilage and subchondral bone. Calcium phosphate cement mixtures were prepared by in situ reaction in a planetary ball mill at aseptic conditions and characterized. It was verified that about 30–60% of amino acids remained adsorbed on hydroxyapatite particles in cements and the addition of amino acids caused around 60% reduction in compressive strength and refinement of hydroxyapatite particles in their microstructure. The significant over-expression of osteogenic genes after the culture of osteoblasts was demonstrated in the cement extracts containing lysine and compared with other cements. The cement pastes were inserted into artificial osteochondral defects in the medial femoral condyle of pigs and, after 3 months post-surgery, tissues were analyzed macroscopically, histologically, immunohistochemically using MRI and X-ray methods. Analysis clearly showed the excellent healing process of artificial osteochondral defects in pigs after treatment with CAL and CAK cements without any inflammation, as well as formation of subchondral bone and hyaline cartilage morphologically and structurally identical to the original tissues. Good integration of the hyaline neocartilage with the surrounding tissue, as well as perfect interconnection between the neocartilage and new subchondral bone tissue, was demonstrated. Tissues were stable after 12 months’ healing.

Repair of large condylar osteochondral defects of the knee by collagen scaffold. Minimum two-year outcomes

IntroductionCollagen scaffolds are a good surgical option for covering large focal osteochondral defects in the knee. In the recent literature there is a wide range of patient profiles and chondral defect treatments (chondral and osteochondral defects, associated procedures, etc.). The aim of the present study was to evaluate clinical and imaging outcomes with collagen scaffolds and to assess any correlation between medium-term clinical outcome and MRI features. The hypothesis was that there is no correlation between clinical outcome and MRI after 2 years postoperatively. Material and methodsA single-center retrospective observational study included all patients receiving a MaioRegen® scaffold for large painful focal osteochondral defect of the femoral condyle. There were 17 patients, with a mean age of 28±9 years. Defect locations comprised 12 medial femoral condyles, 4 lateral femoral condyles and 1 lateral tibial plateau. Mean defect area was 4.5±1.4cm2. All patients were evaluated clinically and on KOOS and objective and subjective IKDC scales, with MRI at last follow-up. ResultsAt a mean follow-up of 46±17 months, mean subjective IKDC was 67.8±23; KOOS scores were: symptoms, 78±22; pain, 78±23; function, 85±20; sports, 66±27; and activities of daily living, 59±25. MRI MOCART score revealed incomplete scaffold healing in 21.4% of cases, with variable signal intensity within regenerated tissue. Functional scores did not correlate with reconstruction aspect on MRI. Discussion/Conclusion3D collagen scaffolds yield good medium-term clinical outcomes in large osteochondral defects of the knee. There is, however, a discrepancy between MRI features of the recipient site and objective and subjective clinical scores. These scaffolds may be a good option for treating large focal osteochondral defects in knees of young patients, but MRI does not provide satisfactory medium-term assessment.

Injectable Microannealed Porous Scaffold for Articular Cartilage Regeneration.

The purpose of this study is to assess the feasibility of a novel microporous annealed particle (MAP) scaffolding hydrogel to enable both articular cartilage and subchondral bone biointegration and chondrocyte regeneration in a rat knee osteochondral defect model. An injectable, microporous scaffold was engineered and modified to match the mechanical properties of articular cartilage. Two experimental groups were utilized-negative saline control and MAP gel treatment group. Saline and MAP gel were injected into osteochondral defects created in the knees of Sprague-Dawley rats. Photo-annealing of the MAP gel was performed. Qualitative histologic and immunohistochemical analysis was performed of the treated defects at 2, 4, and 8 weeks postsurgery. The injectable MAP gel successfully annealed and was sustained within the osteochondral defect at each timepoint. Treatment with MAP gel resulted in maintained size of the osteochondral defect with evidence of tissue ingrowth and increased glycosaminoglycan production, whereas the control defects presented with evidence of disorganized scar tissue. Additionally, there was no significant inflammatory response to the MAP gel noted on histology. We have demonstrated the successful delivery of an injectable, flowable MAP gel scaffold into a rat knee osteochondral defect with subsequent annealing and stable integration into the healing wound. The flowable nature of this scaffold allows for minimally invasive application, for example, via an arthroscopic approach for management of wrist arthritis. The MAP gel was noted to fill the osteochondral defect and maintain the defect dimensions and provide a continuous and smooth surface for cartilage regeneration, suggesting its ability to provide a stable scaffold for tissue ingrowth. Future chemical, mechanical, and biological gel modifications may improve objective evidence of cartilage regeneration.

Allogeneic mesenchymal stem cells and growth factors in gel scaffold repair osteochondral defect in rabbit.

Aim: An attempt was made to improve osteochondral healing with allogeneic mesenchymal stem cells (MSCs) along with certain growth factors. Materials & methods: Induced knee osteochondral defects were filled as: phosphate buffer saline (group A); MSCs in collagen gel (group B); group B plus insulin like growth factor-1 (group C); group C plus transforming growth factor β-1 (group D). Results: Gross and scanning electron microscopy showed superior morphology and surface architecture of the healed tissue in groups D and C. Histologically, group D revealed hyaline cartilage characteristic features followed in order by group C and group B. In all treatment groups, chondrogenic matrix, collagen II2B (col II 2B) and aggrecan were secreted. Conclusion: Combined use of MSCs and growth factors could accelerate osteochondral healing.

Scaffolds for Knee Chondral and Osteochondral Defects: Indications for Different Clinical Scenarios. A Consensus Statement.

To develop patient-focused consensus guidelines on the indications for the use of scaffolds to address chondral and osteochondral femoral condyle lesions. The RAND/UCLA Appropriateness Method (RAM) was used to develop patient-specific recommendations by combining the best available scientific evidence with the collective judgement of a panel of experts guided by a core panel and multidisciplinary discussers. A list of specific clinical scenarios was produced regarding adult patients with symptomatic lesions without instability, malalignment, or meniscal deficiency. Each scenario underwent discussion and a 2-round vote on a 9-point Likert-type scale (range 1-3 "inappropriate," 4-6 "uncertain," 7-9 "appropriate"). Scores were pooled to generate expert recommendations. Scaffold (chondral vs. osteochondral), patient characteristics (age and sport activity level), and lesion characteristics (etiology, size, and the presence of osteoarthritis [OA]) were considered to define 144 scenarios. The use of scaffold-based procedures was considered appropriate in all cases of chondral or osteochondral lesions when joints are not affected by OA, while OA joints presented more controversial results. The analysis of the evaluated factors showed a different weight in influencing treatment appropriateness: the presence of OA influenced 58.3% of the indications, while etiology, size, and age were discriminating factors in 54.2%, 29.2%, and 16.7% of recommendations, respectively. The consensus identified indications still requiring investigation, but also the convergence of the experts in several scenarios defined appropriate or inappropriate, which could support decision making in the daily clinical practice, guiding the use of scaffold-based procedures for the treatment of chondral and osteochondral knee defects.