Full-thickness Cartilage Defects Research Articles

Save the subchondral bone plate: Debridement versus bone marrow stimulation in acetabular cartilage defects over 60 months of follow-up.

Bone marrow stimulation is a common treatment for full-thickness cartilage defects in the hip joint. However, common procedures may result in poor fibrous repair tissue and changes to the subchondral anatomy. This study investigated the clinical outcome of a cohort of International Cartilage Repair Society (ICRS) grades 3 and 4 cartilage defects treated with bone marrow stimulation compared to those who received simple debridement/chondroplasty. In this retrospective registry study, 236 patients with uni-focal acetabular chondral lesions of the hip up to 400 mm² (mean 177.4 ± 113.4 mm²) and of ICRS grade ≥3 with follow-up of at least 12 months (mean 33.2 ± 15.3 months) were included. Eighty-one patients underwent bone marrow stimulation (microfracture: n = 44, abrasion: n = 37) besides treatment of the underlying pathology, 155 patients underwent defect debridement/chondroplasty. The patient-reported outcome was measured using the International Hip Outcome Tool 33 (iHOT33) score and the Visual Analogue Scale (VAS) for pain. iHOT33 and VAS both improved highly statistically significantly (p < 0.001) in the debridement group after 6, 12, 24, 36 and 60 months compared to the preoperative scores, whereas iHOT33 and VAS after microfracture or abrasion did not show statistically significant changes over time. Twenty-four and sixty months postsurgery the debridement group revealed significant higher scores in the iHOT33 compared to the bone marrow stimulation groups. Patients with chondral lesions of the hip ≤400 mm2 sustainably benefit from arthroscopic debridement under preservation of the subchondral bone plate in terms of functional outcome and pain in contrast to patients treated with bone marrow stimulation. These findings discourage the currently recommended use of microfracture in the hip joint. Level III.

Fresh osteochondral allograft transplantation for knee full-thickness articular cartilage lesions using femoral head of living donors: short-term results.

Fresh osteochondral allograft transplantation is a good treatment option of cartilage defects. However, this treatment option is not available in all countries due to limited graft availability and tissue banks limitations. The purpose of this study is to assess the short term functional and imaging outcomes of fresh osteochondral allograft transplantation in the knee using the femoral head of living donors. Fresh osteochondral allografts from the femoral heads of living donors is a valid graft source for management of distal Femur cartilage defects. This technique can improve functional knee scores with good radiological outcomes. Prospective case series. Fifteen patients with full thickness cartilage defects of the distal femur underwent osteochondral allograft transplantation from the femoral heads of living donors. Grafts were transplanted by both shell and multiple dowels techniques. The average follow up duration was 18.3 months (range, 12-25 months). Patients were evaluated by Lysholm and International Knee Documentation Committee (IKDC) scores, radiography and MR imaging using Osteochondral Allograft MRI Scoring System (OCAMRISS). There was a statistically significant improvement (P < 0.001) in both Lysholm and IKDC average scores at 6 months and 12 months postoperative. Postoperative MRI was done at an average 6.8 months (range, 5-11 months) postoperative. The mean total OCAMRISS score was 3.4 (range, 1-7). A second look arthroscopy was done in four patients and showed intact articular cartilage in all three patients. Femoral head of living donors is a valid new source for fresh osteochondral allograft transplantation of knee osteochondral lesions. Short term results showed improvement in clinical assessment scores. Follow up imaging showed graft incorporation and good MRI scores.

A Systematic Review of Human Amnion Enhanced Cartilage Regeneration in Full-Thickness Cartilage Defects.

Cartilage defects present a significant challenge in orthopedic medicine, often leading to pain and functional impairment. To address this, human amnion, a naturally derived biomaterial, has gained attention for its potential in enhancing cartilage regeneration. This systematic review aims to evaluate the efficacy of human amnion in enhancing cartilage regeneration for full-thickness cartilage defects. An electronic search was conducted on MEDLINE-PubMed, Web of Science (WoS), and the Scopus database up to 27 December 2023 from 2007. A total of 401 articles were identified. After removing 125 duplicates and excluding 271 articles based on predetermined criteria, only 5 articles remained eligible for inclusion in this systematic review. All five eligible articles conducted in vivo studies utilizing rabbits as subjects. Furthermore, analysis of the literature reveals an increasing trend in the frequency of utilizing human amnion for the treatment of cartilage defects. Various forms of human amnion were utilized either alone or seeded with cells prior to implantation. Histological assessments and macroscopic observations indicated usage of human amnion improved cartilage repair outcomes. All studies highlighted the positive results despite using different forms of amnion tissues. This systematic review underscores the promising role of human amnion as a viable option for enhancing cartilage regeneration in full-thickness cartilage defects, thus offering valuable insights for future research and clinical applications in orthopedic tissue engineering.

Outcomes of Particulated Juvenile Articular Cartilage and Association With Defect Fill in Patients With Full-Thickness Patellar Chondral Lesions.

Cartilage restoration procedures for patellar cartilage defects have produced inconsistent results, and optimal management remains controversial. Particulated juvenile articular cartilage (PJAC) allograft tissue is an increasingly utilized treatment option for chondral defects, with previous studies demonstrating favorable short-term outcomes for patellar chondral defects. To identify whether there is an association between defect fill on magnetic resonance imaging (MRI) with functional outcomes in patients with full-thickness patellar cartilage lesions treated with PJAC. Case series; Level of evidence, 4. A retrospective review of prospectively collected data was conducted on patients treated with PJAC for a full-thickness symptomatic patellar cartilage lesion between March 2014 and August 2019. MRI was performed for all patients at 6, 12, and 24 months postoperatively. Patient-reported outcome measures (PROMs) were obtained preoperatively and at 1, 2, and >2 years postoperatively. Clinical outcome scores-including the International Knee Documentation Committee (IKDC) score, the Kujala, the Knee injury and Osteoarthritis Outcome Score-Physical Function Short Form (KOOS-PS), the Knee Injury and Osteoarthritis Outcome Score-Quality of Life (KOOS-QoL), and the Hospital for Special Surgery Pediatric Functional Activity Brief Scale (HSS Pedi-FABS)-were analyzed and evaluated for a relationship with tissue fill on MRI. A total of 70 knees in 65 patients (mean age, 26.6 ± 8.1 years) were identified, of which 68 knees (97%) underwent a concomitant patellar stabilization or offloading procedure. Significant improvements were observed on all postoperative PROM scores at the 1-, 2-, and >2-year follow-up except for the Pedi-FABS, which showed no significant difference from baseline. From baseline to the 2-year follow-up, the KOOS-QoL improved from 24.7 to 62.1, the IKDC improved from 41.1 to 73.5, the KOOS-PS improved from 35.6 to 15, and the Kujala improved from 52 to 86.3. Imaging demonstrated no difference in the rate of cartilage defect fill between the 3-month (66%), 6-month (72%), 1-year (74%), and ≥2-year (69%) follow-ups. No association was observed between PROM scores and the percent fill of cartilage defect on MRI at the 1- and 2-year follow-up. PROM scores were significantly improved at the 2-year follow-up in patients who underwent PJAC for full-thickness patellar cartilage defects. On MRI, a cartilage defect fill of >66% was achieved by 3 months in most patients. In our sample, PROM scores were not significantly associated with the defect fill percentage at the short-term follow-up.

The Synovial Sealant Variant for Minced Cartilage Repair: A Technical Note and Retrospective Study

PurposeCartilage defects are a common pathology in active people and affect quality of life. A common treatment option is treatment with minced cartilage (MC). As conservative therapy has a limited effect, surgical treatments vary in terms of procedure and results. A modified technique for autologous cartilage repair is presented here.MethodMC was modified by adding a synovial sealant. This improves the stability of the graft, allowing the cartilage to proliferate. The synovial tissue has the potential to stimulate the implanted cartilage, which promotes healing and regeneration. The clinical and functional results of the modified technique were examined in a retrospective case series.ResultsThe technique has proven to be reproducible for retropatellar cartilage defects and is both efficient and cost effective. MC with synovial sealing was performed in ten patients with retropatellar cartilage damage. In the conducted cases serious, 10 patients were available for follow-up after 18 ± 3 months. Patients showed good clinical results in terms of pain (VAS = 1.9, KOOS Pain = 89.7), symptoms (KOOS Symptoms = 83.6), and daily activity (KOOS Activity = 96.6).ConclusionThe procedure combines the advantages of autologous cartilage repair with a one-stage surgical approach. It utilizes the regenerative potential of synovial tissue while providing improved mechanical stability. This technique offers a cost-effective, autologous solution for full-thickness cartilage defects, and shows promising clinical results in the medium term.

Hydrogel-based and spheroid-based autologous chondrocyte implantation of the knee show similar 2-year functional outcomes: An analysis based on the German Cartilage Registry (KnorpelRegister DGOU).

To compare short-term patient-reported outcomes (PRO) of two contemporary matrix-associated autologous chondrocyte implantation (M-ACI) products for the treatment of large articular cartilage defects of the knee. A retrospective, registry-based, matched-pair analysis was performed, comparing PRO ofpatients undergoing isolated M-ACI with either Spherox™, a spheroid-based ACI (Sb-ACI), or NOVOCART™Inject, a hydrogel-based ACI product (Hb-ACI), for a focal full-thickness cartilage defect of the knee ≥4 cm2. Matching parameters included age, sex, body mass index, defect size, defect localization, symptom duration and previous surgeries. The Knee Injury and Osteoarthritis Outcome Score (KOOS) and the International Knee Documentation Committee (IKDC) score were obtained up to the 24-month follow-up. The total KOOS response rate and percentage of patients attaining a substantial clinical benefit (SCB) in KOOS subscores were calculated. A total of 45 patients per group were matched. The response rate after 24 months was not significantly different between the groups (Sb-ACI 64.4% vs. Hb-ACI 82.2%, p = 0.057). The number of patients with a SCB at 24 months was not significantly different in any KOOS subscore, despite significantly higher improvement of the total KOOS (14.8 ± 16.2 vs. 21.5 ± 15.4, p = 0.047) and KOOS pain in the Hb-ACI group (12.2 ± 18.6 vs. 20.6 ± 19.1, p = 0.037). The IKDC score in the Hb-ACI group was significantly higher at the 12-and 24-month follow-up (60.7 ± 20.2 vs. 70.9 ± 18.0, p = 0.013). The response rate and number of patients achieving an SCB were not significantly different between patients treated with Sb-ACI or Hb-ACI. Both procedures can achieve favourable 2-year PRO. Hb-ACI was associated with better PRO between 1 and 2 years postoperatively;however, the clinical relevance of this benefit is yet to be proven. III, Retrospective comparative study.

Injectable microspheres adhering to the cartilage matrix promote rapid reconstruction of partial-thickness cartilage defects

An effective treatment for the irregular partial-thickness cartilage defect in the early stages of osteoarthritis (OA) is lacking. Cartilage tissue engineering is effective for treating full-thickness cartilage defects with limited area. In this study, we designed an injectable multifunctional poly(lactic-co-glycolic acid) (PLGA) microsphere to repair partial-thickness cartilage defects. The microsphere was grafted with an E7 peptide after loading the microsphere with kartogenin (KGN) and modifying the outer layer through dopamine self-polymerization. The microsphere could adhere to the cartilage defect, recruit synovial mesenchymal stem cells (SMSCs) in situ, and stimulate their differentiation into chondrocytes after injection into the articular cavity. Through in vivo and in vitro experiments, we demonstrated the ability of multifunctional microspheres to adhere to cartilage matrix, recruit SMSCs, and promote their differentiation into cartilage. Following treatment, the cartilage surface of the model group with partial-thickness cartilage defect showed smooth recovery, and the glycosaminoglycan content remained normal; the untreated control group showed significant progression of OA. The microsphere, a framework for cartilage tissue engineering, promoted the expression of SMSCs involved in cartilage repair while adapting to cell migration and growth. Thus, for treating partial-thickness cartilage defects in OA, this innovative carrier system based on stem cell therapy can potentially improve therapeutic outcomes. Statement of significanceMesenchymal stem cells (MSCs) therapy is effective in the repair of cartilage injury. However, because of the particularity of partial-thickness cartilage injury, it is difficult to recruit enough seed cells in situ, and there is a lack of suitable scaffolds for cell migration and growth. Here, we developed polydopamine surface-modified PLGA microspheres (PMS) containing KGN and E7 peptides. The adhesion ability of the microspheres is facilitated by the polydopamine layer wrapped in them; thus, the microspheres can adhere to the injured cartilage and recruit MSCs, thereby promoting their differentiation into chondrocytes and accomplishing cartilage repair. The multifunctional microspheres can be used as a safe and potential method to treat partial-thickness cartilage defects in OA.

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.

Implantation of hUCB-MSCs generates greater hyaline-type cartilage than microdrilling combined with high tibial osteotomy.

To compare the outcomes of treating large cartilage defects in knee osteoarthritis using human allogeneic umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC) implantation or arthroscopic microdrilling as a supplementary cartilage regenerative procedure combined with high tibial osteotomy (HTO). This 1-year prospective comparative study included 25 patients with large, near full-thickness cartilage defects (International Cartilage Repair Society grade ≥ IIIB) in the medial femoral condyles and varus malalignment. Defects were treated with hUCB-MSC implantation or arthroscopic microdrilling combined with HTO. The primary outcomes were pain visual analogue scale and International Knee Documentation Committee subjective scores at 12, 24and 48 weeks. Secondary outcomes included arthroscopic, histologicaland magnetic resonance imaging assessments at 1 year. Fifteen and 10 patients were treated via hUCB-MSC implantation and microdrilling, respectively. Baseline demographics, limb alignmentand clinical outcomes did not significantly differ between the groups. Cartilage defects and total restored areas were significantly larger in the hUCB-MSC group (7.2 ± 1.9 vs. 5.2 ± 2.1 cm2, p = 0.023; 4.5 ± 1.4 vs. 3.0 ± 1.6 cm2, p = 0.035). The proportion of moderate-to-strong positive type II collagen staining was significantly higher in the hUCB-MSC group compared to that in the microdrilled group (93.3% vs. 60%, respectively). Rigidity upon probing resembled that of normal cartilage tissue more in the hUCB-MSC group (86.7% vs. 50.0%, p = 0.075). Histological findings revealed a higher proportion of hyaline cartilage in the group with implanted hUCB-MSC (p = 0.041). hUCB-MSC implantation showed comparable clinical outcomes to those of microdrilling as supplementary cartilage procedures combined with HTO in the short term, despite the significantly larger cartilage defect in the hUCB-MSC group. The repaired cartilage after hUCB-MSC implantation showed greater hyaline-type cartilage with rigidity than that after microdrilling. Level II, Prospective Comparative Cohort Study.

The Role of Hyaluronan/Receptor for Hyaluronan-Mediated Motility Interactions in the Modulation of Macrophage Polarization and Cartilage Repair

Hyaluronan (HA), a negatively charged linear glycosaminoglycan, is a key macromolecular component of the articular cartilage extracellular matrix. The differential effects of HA are determined by a spatially/temporally regulated display of HA receptors, such as CD44 and Receptor for Hyaluronan Mediated Motility (RHAMM). HA signaling through CD44 with RHAMM has been shown to stimulate inflammation and fibrotic processes. This study shows an increased expression of RHAMM in pro-inflammatory macrophages. Interfering with HA/RHAMM interactions using a 15mer RHAMM-mimetic, HA binding peptide (P15-1) together with high molecular weight (HMW)HA reduced the expression and release of inflammatory markers and increased the expression of anti-inflammatory markers in pro-inflammatory macrophages. Interfering with HA/RHAMM interactions in vivo during the regeneration of a full thickness cartilage defect after microfracture surgery in rabbits using three intra-articular injections of P15-1 together with HMWHA reduced the number of pro-inflammatory macrophages and increased the number of anti-inflammatory macrophages in the injured knee joint and greatly improved the repair of the cartilage defect compared to intra-articular injections of HMWHA alone. These findings suggest that HA/RHAMM interactions play a key role in cartilage repair/regeneration via stimulating inflammatory and fibrotic events, including increasing the ratio of pro-inflammatory to anti-inflammatory macrophages. Interfering with these interactions reduced inflammation and greatly improved cartilage repair.

Mid-term outcomes of microfracture for the treatment of focal, full-thickness cartilage defects isolated to the humeral head

BackgroundWhile microfracture has been shown to be an effective treatment for chondral lesions in the knee, evidence to support its use for chondral defects in the shoulder is limited to short-term outcomes studies. The purpose of this study is to determine if microfracture provides pain relief and improved shoulder function in patients with isolated focal chondral defects of the humeral head at a minimum 5-year follow-up. MethodsPatients who underwent microfracture procedure for isolated focal chondral defects of the humeral head with a minimum follow-up of 5 years between 02/2006 and 08/2016 were included. At minimum 5-year follow-up, pre- and postoperative Patient Reported Outcome (PRO) measures were collected, including the American Shoulder and Elbow Surgeons (ASES), Single Assessment Numeric Evaluation (SANE), Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH), Short Form–12 (SF-12) Physical Component Summary (PCS), Visual Analog Scale (VAS) for pain, and patient satisfaction level (1=unsatisfied, 10=very satisfied). Demographic, injury, and surgical data were retrospectively reviewed. Surgical failure was defined as revision surgery for humeral chondral defects or conversion to arthroplasty. Kaplan-Maier analysis was performed to determine survivorship at 5 years. ResultsA total of 17 patients met inclusion/exclusion criteria. There were 15 men and 2 women with an average age of 51 years (range 36-69) and an average follow-up of 9.4 years (range 5.0 – 15.8). The median ASES score improved from 62 (range: 22-88) preoperatively to 90 (range: 50-100) postoperatively (p=.011). Median satisfaction was 8 out of 10 (range: 2-10). There was no correlation between patient age or defect size and PROs. Postoperatively, patients reported significant improvements in recreational and sporting activity as well as the ability to sleep on the affected shoulder (p= <0.05). Three patients failed and required revision surgery. The Kaplan-Meier analysis determined an overall survivorship rate of 80% at 5 years. ConclusionThe presented study illustrates significant improvements for PROs, improved ability to perform recreational and sporting activities, and a survival rate of 80% at a mean of 9.4 years after microfracture for focal chondral humeral head defects.

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.

Significant improvements in clinical outcome measures and patient satisfaction after combined all-arthroscopic meniscal allograft transplantation and autologous chondrocyte implantation: A single-centre longitudinal study.

The optimal treatment approach for the complex pathology of meniscal insufficiency and coexisting full-thickness cartilage defects remains unclear. The purpose of this study was to evaluate the viability, safety, and efficacy of this combined surgical approach at medium-term follow-up. This is a single-centre longitudinal study with blinded outcome assessment. All consecutive patients treated with combined all-arthroscopic meniscal allograft transplantation (MAT) with bone bridge fixation and ACI using chondrospheres at our institution between 2001 and 2021 were eligible for inclusion. Twenty patients with an average follow-up of 72.6 ± 34.4 months were included in the statistical analysis. Clinical outcomes were assessed pre- and postoperatively using the IKDC Subjective Knee Form, Lysholm Score, Tegner Activity Scale, KOOS, and Visual Analog Scale (VAS) for patient satisfaction. Failure and reoperation rates were assessed, and cartilage regeneration tissue was evaluated on postoperative MRI. IKDC scores significantly improved from 52.1 ± 16.9 to 68.5 ± 16.3 (p = 0.003). Lysholm scores improved from 61.5 ± 21.7 to 78.5 ± 12.9 (p = 0.004). Tegner scores improved from 3.5 (1-4) to 4.0 (2-6) (p = 0.014). KOOS scores improved significantly across all subcategories, except 'symptoms', where improvements did not reach statistical significance. VAS for overall patient satisfaction showed improvements but did not reach statistical significance. The combined procedure was successful in 17 patients (85%). Eight patients had to undergo reoperation (40%), comprising mostly small, arthroscopic procedures. Seven reoperations were directly attributable to meniscal allograft transplantation (46.7%). Postoperative Magnetic Resonance Observation of Cartilage Repair Tissue scores were 68.9 ± 16.8 (n = 14). Combined arthroscopic MAT and autologous chondrocyte implantation (ACI) is a viable, safe, and effective treatment approach for younger patients with meniscal insufficiency and coexisting full-thickness cartilage damage, where alternative treatment options are limited. The combined surgical procedure achieved significant improvements in clinical outcome measures and patient satisfaction with acceptable failure and high arthroscopic reoperation rates. MAT is the limiting part of this combined procedure, with most failures and reoperations being attributable to MAT, as opposed to ACI. Level III.

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.

The autologous chondral platelet-rich plasma matrix implantation. A new therapy in cartilage repair and regeneration: macroscopic and biomechanical study in an experimental sheep model.

Articular cartilage injuries are a severe problem, and the treatments for these injuries are complex. The present study investigates a treatment for full-thickness cartilage defects called Autologous Chondral Platelet Rich Plasma Matrix Implantation (PACI) in a sheep model. Chondral defects 8 mm in diameter were surgically induced in the medial femoral condyles of both stifles in eight healthy sheep. Right stifles were treated with PACI and an intraarticular injection with a plasma rich in growth factors (PRGF) solution [treatment group (TRT)], while an intraarticular injection of Ringer's lactate solution was administered in left stifles [Control group (CT)]. The limbs' function was objectively assessed with a force platform to obtain the symmetry index, comparing both groups. After 9 and 18 months, the lesions were macroscopically evaluated using the International Cartilage Repair Society and Goebel scales. Regarding the symmetry index, the TRT group obtained results similar to those of healthy limbs at 9 and 18 months after treatment. Regarding the macroscopic assessment, the values obtained by the TRT group were very close to those of normal cartilage and superior to those obtained by the CT group at 9 months. This new bioregenerative treatment modality can regenerate hyaline articular cartilage. High functional outcomes have been reported, together with a good quality repair tissue in sheep. Therefore, PACI treatment might be a good therapeutic option for full-thickness chondral lesions.

Graphene/β-Tricalcium Phosphate Composite Scaffold Facilitates the Repairment of Cartilage Defect in Rabbit Knee Joint

Our research aims to evaluate the repairment of graphene/β-tricalcium phosphate (G/β-TCP) composite scaffold on cartilage defect in rabbit knee joints. The G/β-TCP composite material containing BMSCs was surgically implanted into the femoral condyle of a full-thickness cartilage defect model in rabbits. XRD showed that no difference in the X-ray diffraction characteristics was observed between G/β-TCP and β-TCP. The biomechanical test claimed that the graphene doped β-TCP material processed higher mechanical strength. Scanning electron microscopy showed that the surface of G/β-TCP material was smoother and the texture was denser. The scaffold combined with BMSCs was transplanted into the full-thickness cartilage defect rabbit model and the results showed that the serum CRP level increased only 1 month after implantation, and the Cr level increased at 2 months after implantation, while G/β-TCP material showed rare significant pathological changes on the liver, spleen, kidney, brain, and soft tissue around the operation, which indicated a promising biocompatibility. The expression of type I and II collagen in the cartilage tissue of G/β-TCP treated rabbits was dramatically elevated compared to β-TCP at 2 and 3 months after implantation. Collectively, the G/β-TCP composite scaffold facilitated the repairment of cartilage defects in the rabbit knee joints.

A New Bioactive Fibrin Formulation Provided Superior Cartilage Regeneration in a Caprine Model

The effective and long-term treatment of cartilage defects is an unmet need among patients worldwide. In the past, several synthetic and natural biomaterials have been designed to support functional articular cartilage formation. However, they have mostly failed to enhance the terminal stage of chondrogenic differentiation, leading to scar tissue formation after the operation. Growth factors substantially regulate cartilage regeneration by acting on receptors to trigger intracellular signaling and cell recruitment for tissue regeneration. In this study, we investigated the effect of recombinant insulin-like growth factor 1 (rIGF-1), loaded in fibrin microbeads (FibIGF1), on cartilage regeneration. rIGF-1-loaded fibrin microbeads were injected into full-thickness cartilage defects in the knees of goats. The stability, integration, and quality of tissue repair were evaluated at 1 and 6 months by gross morphology, histology, and collagen type II staining. The in vivo results showed that compared to plain fibrin samples, particularly at 6 months, FibIGF1 improved the functional cartilage formation, confirmed through gross morphology, histology, and collagen type II immunostaining. FibIGF1 could be a promising candidate for cartilage repair in the clinic.

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.