Full-thickness Chondral Defects Research Articles

One-Step Cartilage Repair of Full-Thickness Knee Chondral Lesions Using a Hyaluronic Acid-Based Scaffold Embedded With Bone Marrow Aspirate Concentrate: Long-term Outcomes After Mean Follow-up Duration of 14 Years.

One-step cell-based techniques of cartilage repair that lead to restoration of durable chondral tissue and long-term maintenance of joint function are cost-effective and ideal for routine use. To examine the long-term clinical outcomes, after a mean follow-up duration of 14 years, of cartilage repair in the knee using a hyaluronic acid-based scaffold in association with bone marrow aspirate concentrate (HA-BMAC) and to evaluate the effect of age, lesion characteristics, and associated treatments on the outcome of this cartilage repair method. Case series; Level of evidence, 4. Patients were followed prospectively for a mean duration of 14.0 years after undergoing treatment of knee full-thickness articular cartilage injury using HA-BMAC. Clinical evaluation consisted of the patient-reported scoring tools of the visual analog scale and the Knee injury and Osteoarthritis Outcome Score, which were completed preoperatively and at the time of final follow-up. A total of 26 patients with a mean age of 48.3 years (17 male, 9 female) and median chondral lesion size of 6.6 cm2 (range, 1-27 cm2) were followed prospectively. There were 3 treatment failures, and 1 patient who underwent medial compartment unicompartmental arthroplasty 12 years after HA-BMAC treatment of patellar chondral injury. Of the 22 remaining patients, after a mean final follow-up duration of 14.0 years (range, 12-16 years), the median visual analog scale score of 0.6 was significantly decreased from the preoperative median score of 5.0 (P < .001). The median Knee injury and Osteoarthritis Outcome Score Pain (92), Symptoms (86), Activities of Daily Living (96), Sports (85), and Quality of Life (88) subscale values were all increased compared with the preoperative scores (P≤ .001). There was no correlation of clinical outcome score and body mass index. One-step cartilage repair of full-thickness chondral defects in the knee using an HA-BMAC led to successful long-term clinical outcomes and maintenance of joint junction after a mean follow-up duration of 14 years. Long-term clinical success in active, nonobese patients has been uniformly demonstrated across a wide range of patient ages and lesion types, including cases of multicompartment involvement, treatment of associated conditions, and large or bipolar chondral lesions.

Anterior Opening-Wedge Proximal Tibial Osteotomy for Symptomatic Genu Recurvatum and Osteochondral Autograft Transfer for Osteochondral Defect

Acute knee hyperextension injuries are more frequently sustained during athletic trauma and can cause symptomatic pain, soft-tissue laxity of the knee, malalignment, and ligament strain. Decreased posterior tibial slope is correlated with a higher degree of knee hyperextension, and although not the only cause, it can contribute to symptomatic genu recurvatum. In the context of acute knee hyperextension, chondral lesions may occur secondarily but are more often caused by limb malalignment and overuse. In the setting of symptomatic genu recurvatum and an osteochondral defect, it is vital to restore the native joint biomechanics. We describe the use of anterior opening-wedge proximal tibial osteotomy to correct symptomatic genu recurvatum and osteochondral autograft transfer to repair a full-thickness chondral defect. Past studies have shown long-term successful functional outcomes for both anterior opening-wedge proximal tibial osteotomy and osteochondral autograft transfer procedures, with most patients returning to their preinjury activity levels.

Patient-Specific Distal Femoral Guides Optimize Cartilage Topography Matching in Osteochondral Allograft Transplantations

Background: Osteochondral allograft (OCA) transplantation is an important surgical technique for full-thickness chondral defects in the knee. For patients undergoing this procedure, topography matching between the donor and recipient sites is essential to limit premature wear of the OCA. Currently, there is no standardized process of donor and recipient graft matching. Purpose: To evaluate a novel topography matching technique for distal femoral condyle OCA transplantation using 3-dimensional (3D) laser scanning to create 3D-printed patient-specific instrumentation in a human cadaveric model. Study Design: Descriptive laboratory study. Methods: Human cadaveric distal femoral condyles (n = 12) underwent 3D laser scanning. An 18-mm circular osteochondral recipient defect was virtually created on the medial femoral condyle (MFC), and the position and orientation of the best topography-matched osteochondral graft from a paired donor lateral femoral condyle (LFC) were determined using an in silico analysis algorithm minimizing articular step-off distances between the edges of the graft and recipient defect. Distances between the entire surface of the OCA graft and the underneath surface of the MFC were evaluated as surface mismatch. Donor (LFC) and recipient (MFC) 3D-printed patient-specific guides were created based on 3D reconstructions of the scanned condyles. Through use of the guides, OCAs were harvested from the LFC and transplanted to the reamed recipient defect site (MFC). The post-OCA recipient condyles were laser scanned. The 360° articular step-off and cartilage topography mismatch were measured. Results: The mean cartilage step-off and graft surface mismatch for the in silico OCA transplant were 0.073 ± 0.029 mm (range, 0.005-0.113 mm) and 0.166 ± 0.039 mm (range, 0.120-0.243 mm), respectively. Comparatively, the cadaveric specimens postimplant had significantly larger step-off differences (0.173 ± 0.085 mm; range, 0.082-0.399 mm; P = .001) but equivalent graft surface topography matching (0.181 ± 0.080 mm; range, 0.087-0.396 mm; P = .678). All 12 OCA transplants had mean circumferential step-off differences less than a clinically significant cutoff of 0.5 mm. Conclusion: These findings suggest that the use of 3D-printed patient-specific guides for OCA transplantation has the ability to reliably optimize cartilage topography matching for LFC to MFC transplantation. This study demonstrated substantially lower step-off values compared with previous orthopaedic literature when also evaluating LFC to MFC transplantation. Using this novel technique in a model performing MFC to MFC transplantation has the potential to yield further enhanced results due to improved radii of curvature matching. Clinical Relevance: Topography-matched graft implantation for focal chondral defects of the knee in patients improves surface matching and has the potential to improve long-term outcomes. Efficient selection of the allograft also allows improved availability of the limited allograft sources.

Poster 296: Comparing Outcomes of Osteochondral Allograft Transplantation of the Knee Preserved by the Missouri Osteochondral Preservation System to Standard Preservation Methods

Objectives: Osteochondral allograft (OCA) transplantation is an established surgical intervention for full-thickness chondral defects. Standard Preservation (SP) protocols currently allow for osteochondral allografts to be stored for a maximum of 28 days after procurement. The Missouri Osteochondral Allograft Preservation System allows for grafts to be stored for at least 60 days after procurement. The purpose of this study is to compare clinical and radiographic outcomes in patients that have undergone OCA transplantation utilizing Missouri Osteochondral Allograft Preservation System (MOPS) to standard preservation protocols. Methods: Retrospective review identified all patients who underwent OCA transplantation between 2012 and 2018. Patients without appropriate follow-up, postoperative outcomes, or necessary imaging were excluded. All patients had at least 2-year follow-up data. Patient demographics, outcomes, and graft information were compared between patients who received grafts preserved by MOPS and standard preservation as previously defined. Results: Sixty-four patients were included. Twenty-five were in the MOPS group and 39 in the SP group. Members of the MOPS group were younger at the time of surgery than those in the SP group (28.6 ± 10.7 years in MOPS vs. 36.7 ± 10.9 in SP group, P = 0.005). Seventy-six grafts were analyzed with 39 grafts in the MOPS group and 37 in the SP group. Grafts in the MOPS group were stored longer (average 50.03 days) than grafts in the SP group (average 23.18 days) (P &lt; 0.001). No difference between groups was found in complications or reoperation rates. Outcomes between the 2 groups showed no statistical differences for complications or revisions as well as similar Knee Injury and Osteoarthritis Outcome Scores for Joint Replacement, International Knee Documentation Committee scores, 12-item psychosocial safety climate scores, and 12-item mental health component summary scores. Conclusions: Grafts preserved using the MOPS were stored for more than double the length of time than grafts preserved with standard preservation techniques. There was no difference in postoperative outcomes following OCA transplantation regardless of preservation method used.

Rapid Recovery after Reparation of Full-Thickness Chondral Defects of the Knee with the Use of Hyaluronan (HA)-Based 3-D Scaffold.

Articular cartilage injuries are found in up to 60% of patients who undergo an arthroscopic knee procedure, and those that totally affect articular cartilage (grade IV) have limited regenerative capacity and extended time for recovery. 3-D scaffolds represent a novel solution to address this type of injury. Our purpose was to analyze the MRI findings and functional status of patients that underwent repair of chondral defects either by microfractures or Hyaluronan (HA) 3-D scaffolding. We conducted a retrospective study of patients with chondral defects. The outcomes analyzed in this study included anatomical changes evaluated by the Henderson score (based on MRI findings) at baseline, 6, and 12 months after surgery, and improvement in functionality evaluated by the Modified Cincinnati Knee Rating System (MCKRS) at baseline and 6 months after surgery. Clinical and demographic characteristics were similar for both groups. There was a statistically significant improvement in Henderson score for the 3-D scaffold-treated group at 6 months versus the microfracture group (p < 0.0001). Improvement in functionality, measured by the MCKRS, was more frequently found in the 3-D scaffold-treated group. In conclusion, the use of HA 3-D scaffolding was superior, with faster recovery evident 6 months after the surgery that progressed to full recovery in all patients a year after surgery. Future studies with a randomized design might help to support our findings. This study provides level III evidence.

Young Age and Concomitant or Prior Bony Realignment Procedures are Associated with Decreased Risk of Failure of Osteochondral Allograft Transplantation in the Knee: A Nationwide Database Study.

Osteochondral allograft (OCA) transplantation is a restorative surgical option for large, full-thickness chondral or osteochondral defects in the knee. Variability in outcomes reporting has led to a broad range of graft survival rates. Using rate of salvage surgery following OCA as a failure metric, the purpose of this study was to analyze the incidence and risk factors for failure in a nationwide cohort. The M151Ortho PearlDiver database was queried for patients aged 20 to 59 who underwent primary OCA between 2010 and 2020. Patients with prior cartilage procedures or arthroplasty were excluded. Kaplan-Meier survival analysis was performed to characterize cumulative rate of salvage surgery, defined as any patient subsequently undergoing revision OCA, autologous chondrocyte implantation (ACI), osteochondral autograft transfer system (OATS), unicompartmental knee arthroplasty (UKA), or total knee arthroplasty (TKA). Multivariable logistic regression was used to determine the effect of several variables on odds of salvage surgery. Around 6,391 patients met inclusion criteria. Cumulative 5-year salvage rate was 1.71%, with 68.8% in the first 2 years. Age 20 to 29 and concomitant or prior bony realignment procedures were associated with significantly decreased rate of salvage surgery (age-adjusted odds ratio [aOR] = 0.49, 95% confidence interval [CI], 0.24-0.99, P = 0.046; realignment-aOR = 0.24, 95% CI, 0.04-0.75, P = 0.046). In the largest OCA cohort studied to date, less than 2% of patients required salvage surgery. Young age and bony realignment were protective. These findings suggest that OCA in the knee is a durable cartilage-restoration procedure, especially in young patients with corrected alignment.

Osteochondral Allograft and Concurrent Meniscal Allograft Transplantation

Background: Symptomatic, full-thickness chondral defects often are associated with meniscal deficiencies. These are difficult problems to manage in the young, high-demand patient population. A number of differing techniques have been published with no consensus. While more recent techniques have favored minimally invasive approaches, an open approach with tubercle osteotomy to maximize visualization of all knee compartments can still provide favorable outcomes when using a careful technique and postoperative protocol. Indications: Young, high-demand patients with long-standing meniscal deficiency and resultant chondral defects are indicated for cartilage restoration and preservation procedures. A meniscal allograft transplantation is indicated in symptomatic patients with prior total or subtotal meniscectomy. It is important to address other concomitant pathology such as instability, alignment, and chondral defects. Concomitant procedures are often performed with meniscal transplants, including osteochondral allograft transplantation for larger defects. Technique Description: This surgical technique video demonstrates a tibial tubercle osteotomy approach to gain access to both the medial and lateral tibiofemoral compartments. An arthroscopic-assisted bone slot technique was performed for meniscal allograft transplantation. Appropriately sized osteochondral allograft bone plugs were then transplanted onto the medial and femoral condyles with a press fit technique. Results: At 1-year follow-up, the presented patient has regained full motion and are back to full activities. Discussion/Conclusion: Full-thickness chondral defects associated with meniscal deficiency in a young, high-demand patient is a difficult problem to manage. Recent results using minimally invasive approaches have demonstrated favorable mid- and long-term outcomes. In patients with pathology that may preclude a minimally invasive approach, an open technique with osteotomy can still have a promising outcome. 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.

HOW DOES TIBIOFEMORAL CONTACT PRESSURE DEFINE STRESS CONTACT LIMITS IN THE PRESENCE OF FULL-THICKNESS CHONDRAL DEFECT SIZE ON THE MEDIAL AND LATERAL CONDYLE AT FULL EXTENSION?

Chondral defects in the knee have cartilage biomechanical differences due to defect size and orientation. This study examines how the tibiofemoral contact pressure is affected by increasing full-thickness chondral defect size on the medial and lateral condyle at full extension.Isolated full-thickness, square chondral defects increasing from 0.09cm2 to 1.0cm2 were created sequentially on the medial and lateral femoral condyles of six human cadaveric knees with intact ligaments and menisci. Chondral defects were created 1.0cm from the femoral notch posteriorly. The knees were fixed to a uniaxial load frame and loaded from 0N to 600N at full extension. Contact pressures between the femoral and tibial condyles were measured using pressure mapping sensors. The peak contact pressure was defined as the highest value in the 2.54mm2 area around the defect. The location of the peak contact pressure was determined relative to the centre of the defect.Peak contact pressure was significantly different between (4.30MPa) 0.09cm2 and (6.91MPa) 1.0cm2 defects (p=0.04) on the medial condyle. On the lateral condyle, post-hoc analysis showed differences in contact pressures between (3.63MPa) 0.09cm2 and (5.81MPa) 1.0cm2 defect sizes (p=0.02).The location of the stress point shifted from being posteromedial (67% of knees) to anterolateral (83%) after reaching a 0.49cm2 defect size (p &lt; 0.01) in the medial condyle. Conversely, the location of the peak contact pressure point moved from being anterolateral (50%) to a posterolateral (67%) location in defect sizes greater than 0.49cm2 (p &lt; 0.01).Changes in contact area redistribution and cartilage stress from 0.49cm2 to 1.0cm2 impact adjacent cartilage integrity. The location of the maximum stress point also varied with larger defects. This study suggests that size cutoffs exist earlier in the natural history of chondral defects, as small as 0.49cm2, than previously studied, suggesting a lower threshold for intervention.

Cartilage-targeting mRNA-lipid nanoparticles rescue perifocal apoptotic chondrocytes for integrative cartilage repair

Integration of repair tissue with host cartilage is challenging. The persistent and drastic hypocellular interface resulting from perifocal chondrocyte apoptosis, leads to failure of cartilage repair over time. Recombinant insulin-like growth factor-1 (IGF-1) has been shown to inhibit chondrocyte apoptosis in vitro. However, low bioactivity, limited penetration and short retention are its drawbacks. Herein, a cartilage targeting ionizable lipid nanoparticle (LNP) is developed. Messenger RNA (mRNA) encoding IGF-1 is chemically modified and encapsulated by LNP (mRNA-LNP). CAQK, a peptide previously used for targeted delivery to the central nervous system, is introduced to mRNA-LNP (mRNA-cLNP) to bind aggrecan enriched in cartilage. As a result, mRNA-cLNP exhibits improved penetration of cartilage and prolonged retention in the joint cavity. The mRNA-cLNP also showed robust reversal of chondrocyte apoptosis. In a full-thickness chondral defect plus microfracture model, mRNA-cLNP maintained interfacial cellularity and prevented matrix degradation in cartilage-cartilage interface. This study shows that mRNA-cLNP is a promising therapeutic agent for integrative cartilage repair.

Effect of Bone Morphogenetic Protein–2 Combined With Microfracture for Osteochondral Defect of the Talus in a Rabbit Model

Background: Osteochondral defects of the talus can be effectively treated using microfracture, which is technically safe, accessible, and affordable. However, fibrous tissue and fibrocartilage comprise the majority of tissue repairs resulting from these procedures. These tissue types lack the mechanical characteristics of native hyaline cartilage and might significantly contribute to the decline in long-term outcomes. Recombinant human-bone morphogenetic protein–2 (rhBMP-2) has been shown to promote matrix synthesis and increase cartilage formation, thus enhancing chondrogenesis in vitro. Purpose: This study aimed to evaluate the treatment ability of combining rhBMP-2 with microfracture in rabbit talus osteochondral defect. Study Design: Controlled laboratory study. Methods: A full-thickness chondral defect (3 × 3 × 2 mm) was constructed in the center talar dome of 24 New Zealand White male rabbits, which were then divided into 4 groups of 6. Each group received the appropriate treatment: group 1 (control; no treatment of defect), group 2 (microfracture treatment), group 3 (rhBMP-2/hydroxyapatite treatment), and group 4 (microfracture combined with rhBMP-2/hydroxyapatite treatment). Animals were sacrificed at 2, 4, and 6 weeks postoperatively. The International Cartilage Regeneration & Joint Preservation Society macroscopic score, which considers the degree of defect repair, the integration to the border zone, and the macroscopic appearance, was used to assess the repaired tissue’s macroscopic appearance. Subchondral bone regeneration in defects was analyzed using micro–computed tomography, and the histological findings were graded using a modified version of the Wakitani scoring system for osteochondral repair. Results: At 2, 4, and 6 weeks, micro-computed tomography analysis revealed that groups 3 and 4 exhibited subchondral bone healing that was more significantly improved compared with groups 1. No sample showed excessive bone growth from the subchondral bone area. According to macroscopic and histological results, group 4 showed higher-quality cartilage and more accelerated cartilage regeneration than the other groups over time. Conclusion: These findings show that osteochondral defect repair in a rabbit talus model could be effectively accelerated and improved by combining rhBMP-2 with microfracture. Clinical Relevance: Using rhBMP-2 in combination with microfracture may enhance the repair of talar osteochondral lesions.

The Effect of Injection of Secretome of Umbilical Cord Mesenchymal Stem Cells in Articular Cartilage Repair in Sheep Model.

Articular cartilage is an avascular, aneural, and lymphatic tissue with limited capacity to regenerate. Numerous techniques have been employed to repair or regenerate; however, the success rate varies. In fact, most of them result in the formation of fibrocartilage, not hyaline cartilage. The future of treating cartilage defects lies in providing biological solutions through cartilage regeneration. Mesenchymal stem cells (MSCs) represent a promising therapy for cartilage regeneration. These cells secrete factors that enhance cartilage repair. This study studied the effects of intra-articular injection of human umbilical cord MSC (hUC-MSC) secretome on cartilage damage in a sheep model. Standardized rectangular (5x5 mm) full-thickness chondral defects were created in the lateral femoral condyle of 15 adult sheep and debrided down to the subchondral bone plate. Three treatment groups were tested: 4 microfracture perforations using 1.0mm diameter awls (group 1), intra-articular injection of hUC-MSC secretome (group 2), and a combination of microfracture and intra-articular injection of hUC-MSC secretome (group 3). The osteochondral repair was assessed at 6 months using an established macroscopic and histological analyses. Macroscopically, combined therapy application shows significant cartilage repair improvement compared to microfracture alone (p=0.004). Microscopically, the application of combined therapy shows significant improvement of cartilage repair compared to secretome injection alone (p=0.031). Microfracture combined with injection of hUCB-MSCs secretome could be an effective alternative for repairing articular cartilage defects in vivo.

Clinical and Magnetic Resonance Imaging Outcomes After Human Cord Blood–Derived Mesenchymal Stem Cell Implantation for Chondral Defects of the Knee

There is a paucity of literature reporting clinical and magnetic resonance imaging (MRI) outcomes after allogeneic umbilical cord blood-derived mesenchymal stem cell (UCB-MSC) implantation for chondral defects of the knee. To report clinical and MRI outcomes after UCB-MSC implantation for chondral lesions of the knee. Case series; Level of evidence, 4. Inclusion criteria were patients aged between 40 and 70 years with focal chondral lesions of grade 3 or 4 on the medial femoral condyle, defect sizes >4 cm2, and intact ligaments. Exclusion criteria were patients who required realignment osteotomy or who had a meniscal deficiency, ligamentous instability, or a concomitant full-thickness chondral defect in the lateral or patellofemoral compartment. A mixture of human UCB-MSCs and sodium hyaluronate was implanted into the chondral defect through mini-arthrotomy. MRI at 1-year follow-up was performed to evaluate repaired cartilage hypertrophy. Repaired cartilage thickness was measured, and hypertrophy was classified as grade 1 (<125%), grade 2 (<150%), or grade 3 (<200%). Patient-reported outcomes (PROs; International Knee Documentation Committee, visual analog scale for pain, and Western Ontario and McMaster Universities Osteoarthritis Index) were evaluated preoperatively and at 1, 2, and 3 years postoperatively. Repaired cartilage hypertrophy was evaluated for a correlation with PRO scores. Enrolled were 85 patients with a mean age of 56.8 ± 6.1 years and a mean chondral defect size of 6.7 ± 2.0 cm2. At follow-up, a significant improvement in all PRO scores was seen compared with preoperatively (P < .001 for all). MRI at 1-year follow-up demonstrated that 28 patients had grade 1 repaired cartilage hypertrophy, 41 patients had grade 2, and 16 patients had grade 3. MRI performed in 11 patients at 2 years after surgery indicated no difference in repaired cartilage hypertrophy between the 1- and 2-year time points. The grade of repaired cartilage hypertrophy did not correlate with PRO scores. Clinical outcomes improved significantly at short-term follow-up after UCB-MSC implantation. Although all patients showed repaired cartilage hypertrophy, it did not correlate with clinical outcomes.

Intra-osseous plasma rich in growth factors enhances cartilage and subchondral bone regeneration in rabbits with acute full thickness chondral defects: Histological assessment.

Intra-articular (IA) combined with intra-osseous (IO) infiltration of plasma rich in growth factors (PRGF) have been proposed as an alternative approach to treat patients with severe osteoarthritis (OA) and subchondral bone damage. The aim of the study is to evaluate the efficacy of IO injections of PRGF to treat acute full depth chondral lesion in a rabbit model by using two histological validated scales (OARSI and ICRS II). A total of 40 rabbits were included in the study. A full depth chondral defect was created in the medial femoral condyle and then animals were divided into 2 groups depending on the IO treatment injected on surgery day: control group (IA injection of PRGF and IO injection of saline) and treatment group (IA combined with IO injection of PRGF). Animals were euthanized 56 and 84 days after surgery and the condyles were processed for posterior histological evaluation. Better scores were obtained in treatment group in both scoring systems at 56- and 84-days follow-up than in control group. Additionally, longer-term histological benefits have been obtained in the treatment group. The results suggests that IO infiltration of PRGF enhances cartilage and subchondral bone healing more than the IA-only PRGF infiltration and provides longer-lasting beneficial effects.

Correlation of Arthroscopic Grading and Optical Coherence Tomography as Markers of Early Repair and Predictors of Later Healing Evident on MRI and Histomorphometric Assessment of Cartilage Defects Implanted with Chondrocytes Overexpressing IGF-I.

Injury of articular cartilage is common, and due to the poor intrinsic capabilities of chondrocytes, it can precipitate joint degradation and osteoarthritis (OA). Implantation of autologous chondrocytes into cartilaginous defects has been used to bolster repair. Accurate assessment of the quality of repair tissue remains challenging. This study aimed to investigate the utility of noninvasive imaging modalities, including arthroscopic grading and optical coherence tomography (OCT) for assessment of early cartilage repair (8 weeks), and MRI to determine long-term healing (8 months). Large (15 mm diameter), full-thickness chondral defects were created on both lateral trochlear ridges of the femur in 24 horses. Defects were implanted with autologous chondrocytes transduced with rAAV5-IGF-I, autologous chondrocytes transduced with rAAV5-GFP, naïve autologous chondrocytes, or autologous fibrin. Healing was evaluated at 8 weeks post-implantation using arthroscopy and OCT, and at 8 months post-implantation using MRI, gross pathology, and histopathology. OCT and arthroscopic scoring of short-term repair tissue were significantly correlated. Arthroscopy was also correlated with later gross pathology and histopathology of repair tissue at 8 months post-implantation, while OCT was not correlated. MRI was not correlated with any other assessment variable. This study indicated that arthroscopic inspection and manual probing to develop an early repair score may be a better predictor of long-term cartilage repair quality following autologous chondrocyte implantation. Furthermore, qualitative MRI may not provide additional discriminatory information when assessing mature repair tissue, at least in this equine model of cartilage repair.

Cell transplantation techniques for cartilage restoration

BackgroundFocal articular chondral lesions are a common finding among patients presenting with knee pain. If symptomatic and unresponsive to conservative treatment, cell transplantation techniques offer a unique solution to address larger defects by engineering chondrocytes to integrate within the subchondral bone of the lesion and regenerate cartilage. ObjectivesThe purpose of this article is to review the evaluation of, and clinical decision making for, patients being considered for cell transplantation and the available techniques an orthopaedic surgeon has at their disposal. MethodsA review of recent literature regarding cartilage defects in the knee and cell transplantation techniques was performed to provide strategies for evaluating and treating chondral defects with matrix-induced autologous chondrocyte implantation (MACI) or particulated juvenile allograft cartilage (PJAC) procedures. ResultsChondral defects in the knee can be treated with patients’ own chondrocytes embedded into a collagen membrane as a MACI procedure, or minced autologous donor cartilage that is then implanted onto a scaffold as a PJAC procedure. These cell transplantation techniques offer advantages compared to bone marrow stimulation or mosaicplasty, and have shown clinically significant improvements in outcome scores with low rates of complications. ConclusionCell transplantation techniques such as MACI and PJAC offer treatment options that can effectively address large full-thickness chondral defects in the tibiofemoral joint or patellofemoral joint that may respond poorly to bone marrow stimulation or mosaicplasty.

Particulate cartilage and platelet-rich plasma treatment for knee chondral defects in sheep

PurposeArticular cartilage is vulnerable to multiple types of damage and it has limited reparative and regenerative capacities due to its absence of vascularity. Although a large number of therapeutic strategies exist to treat chondral defects, they have some limitations, such as fibrocartilage formation. Therefore, the goal of the present study was to evaluate the chondrogenic regenerative properties of an autologous-made matrix of particulated cartilage and platelet-rich plasma (PACI + PRP) implantation for the treatment of full-thickness chondral defects in sheep.MethodsA full-thickness 8 mm diameter cartilage defect was created in the weight-bearing area of the medial femoral condyle in both knees of 16 sheep. The right knees of all animals were treated with particulated autograft cartilage implantation and platelet-rich plasma, while the left knees were injected with Ringer’s lactate solution or hyaluronic acid. The sheep were killed 9 or 18 months after surgery. Macroscopic evaluations were performed using three different scoring systems, and histopathological evaluations were performed using a modified scoring system based on different scoring systems.ResultsThe PACI + PRP groups showed statistically significant differences in the percentage of defect repair and chondrocytes in the newly formed cartilage tissue at 18 months compared to 9 months.ConclusionsThe results suggest that macroscopic appearance, histological structure and chondrocyte repair were improved when using PACI + PRP treatment for chondral defects, producing an outcome similar to the surrounding healthy cartilage. PACI + PRP is a totally autologous, easy, and unexpensive treatment that can be performed in one-step procedure and is useful as a therapeutic option for knee chondral defects.

Small Chondral Defects Affect Tibiofemoral Contact Area and Stress: Should a Lower Threshold Be Used for Intervention?

Chondral defects in the knee have biomechanical differences because of defect size and location. Prior literature only compares the maximum stress experienced with large defects. It was hypothesized that pressure surrounding the chondral defect would increase with size and vary in location, such that a size cutoff exists that suggests surgical intervention. Controlled laboratory study. Isolated chondral defects from 0.09 to 1.0 cm2 were created on the medial and lateral femoral condyles of 6 human cadaveric knees. The knees were fixed to a uniaxial load frame and loaded from 0 to 600 N at full extension. Another defect was created at the point of tibiofemoral contact at 30° of flexion. Tibiofemoral contact pressures were measured. Peak contact pressure was the highest value in the area delimited within a 3-mm rim around the defect. The location of the peak contact pressure was determined. At full extension, the mean maximum pressures on the medial femoral condyle ranged from 4.30 to 6.91 MPa at 0.09 and 1.0 cm2, respectively (P < .01). The location of the peak pressure was found posteromedial in defects between 0.09 and 0.25 cm2, shifting anterolaterally at sizes 0.49 and 1.0 cm2 (P < .01). The maximum pressures on the lateral femoral condyle ranged from 3.63 to 5.81 MPa at 0.09 and 1.0 cm2, respectively (P = .02). The location of the peak contact pressure point was anterolateral in defects between 0.09 and 0.25 cm2, shifting posterolaterally at 0.49 and 1.0 cm2 (P < .01). No differences in contact pressure between full extension and 30° of flexion were found for either the lateral or medial condyles. Full-thickness chondral defects bilaterally had a significant increase in contact pressure between defect sizes of 0.49 and 1.0 cm2. The location of the maximum contact pressures surrounding the lesion also varied with larger defects. Contact area redistribution and cartilage stress change may affect adjacent cartilage integrity. Size cutoffs may exist earlier in the natural history of chondral defects than previously realized, suggesting a lower threshold for intervention.

In Situ Assessment of Porcine Osteochondral Repair Tissue in the Visible-Near Infrared Spectral Region.

Standard assessment of cartilage repair progression by visual arthroscopy can be subjective and may result in suboptimal evaluation. Visible–near infrared (Vis-NIR) fiber optic spectroscopy of joint tissues, including articular cartilage and subchondral bone, provides an objective approach for quantitative assessment of tissue composition. Here, we applied this technique in the 350–2,500 nm spectral region to identify spectral markers of osteochondral tissue during repair with the overarching goal of developing a new approach to monitor repair of cartilage defects in vivo. Full thickness chondral defects were created in Yucatan minipigs using a 5-mm biopsy punch, and microfracture (MFx) was performed as a standard technique to facilitate repair. Tissues were evaluated at 1 month (in adult pigs) and 3 months (in juvenile pigs) post-surgery by spectroscopy and histology. After euthanasia, Vis-NIR spectra were collected in situ from the defect region. Additional spectroscopy experiments were carried out in vitro to aid in spectral interpretation. Osteochondral tissues were dissected from the joint and evaluated using the conventional International Cartilage Repair Society (ICRS) II histological scoring system, which showed lower scores for the 1-month than the 3-month repair tissues. In the visible spectral region, hemoglobin absorbances at 540 and 570 nm were significantly higher in spectra from 1-month repair tissue than 3-month repair tissue, indicating a reduction of blood in the more mature repair tissue. In the NIR region, we observed qualitative differences between the two groups in spectra taken from the defect, but differences did not reach significance. Furthermore, spectral data also indicated that the hydrated environment of the joint tissue may interfere with evaluation of tissue water absorbances in the NIR region. Together, these data provide support for further investigation of the visible spectral region for assessment of longitudinal repair of cartilage defects, which would enable assessment during routine arthroscopy, particularly in a hydrated environment.

Incidence, Timing, and Risk Factors for 5-Year Revision Surgery After Autologous Chondrocyte Implantation in 533 Patients

Background: Autologous chondrocyte implantation (ACI) can be used to treat focal, full-thickness chondral defects of the knee. However, there is limited large-sample evidence available regarding the incidence, timing, and risk factors for revision surgery after ACI. Purpose: To assess the 5-year incidence, timing, and risk factors for revision surgery after ACI in a large national cohort. Study Design: Case series; Level of evidence, 4. Methods: The 2010-2020 PearlDiver database was queried for patients aged 20 to 59 years who underwent primary ACI of the knee without previous chondral procedures or knee arthroplasty. Revision surgery was defined as subsequent revision ACI, osteochondral allograft transplantation, osteochondral autograft transfer, unicompartmental knee arthroplasty, or total knee arthroplasty within 5 years. Kaplan-Meier analysis was used to assess both incidence and timing of revision surgery. Risk factors evaluated for revision surgery included patient age, sex, body mass index (BMI), Elixhauser Comorbidity Index (ECI) score, and previous or concomitant bony realignment procedures. Results: In total, 533 patients underwent primary ACI and met inclusion criteria. The 5-year incidence of revision surgery was 10.3%, with 63% of revisions occurring in the first 2 years after surgery. Risk factors associated with revision surgery included female sex (odds ratio, 2.58; 95% CI, 1.22-5.45; P = .013) and BMI ≥35 (odds ratio, 2.24; 95% CI, 1.01-4.94; P = .047). There was no relationship between age, ECI score, or previous or concomitant bony realignment procedures and revision surgery at 5 years (P > .05). Conclusion: In an analysis of 533 patients who underwent ACI, 10.3% required a subsequent articular cartilage procedure or conversion to knee arthroplasty in the first 5 postoperative years. Revision surgery was greatest in the first 2 postoperative years. Female sex and severe obesity (BMI, ≥35) were associated with increased risk of revision surgery, while age, ECI score, and previous or concomitant bony realignment procedures were not. These findings suggest that treatment of chondral defects of the knee with ACI is associated with durable outcomes at the 5-year follow-up.

Subchondral Drilling Independent of Drill Hole Number Improves Articular Cartilage Repair and Reduces Subchondral Bone Alterations Compared With Debridement in Adult Sheep

Background: Subchondral drilling is an established marrow stimulation technique for small cartilage defects, but whether drilling is required at all and if the drill hole density affects repair remains unclear. Hypotheses: Osteochondral repair is improved when the subchondral bone is perforated by a higher number of drill holes per unit area, and drilling is superior to defect debridement alone. Study Design: Controlled laboratory study. Methods: Rectangular full-thickness chondral defects (4 × 8 mm) were created in the trochlea of adult sheep (N = 16), debrided down to the subchondral bone plate without further treatment as controls (no treatment; n = 7) or treated with either 2 or 6 (n = 7 each) subchondral drill holes (diameter, 1.0 mm; depth, 10.0 mm). Osteochondral repair was assessed at 6 months postoperatively by standardized (semi-)quantitative macroscopic, histological, immunohistochemical, biochemical, and micro–computed tomography analyses. Results: Compared with defect debridement alone, histological overall cartilaginous repair tissue quality (P = .025) and the macroscopic aspect of the adjacent cartilage (P≤ .032) were improved after both drilling densities. Only drilling with 6 holes increased type 2 collagen content in the repair tissue compared with controls (P = .038). After debridement, bone mineral density was significantly decreased in the subchondral bone plate (P≤ .015) and the subarticular spongiosa (P≤ .041) compared with both drilling groups. Debridement also significantly increased intralesional osteophyte sectional area compared with drilling (P≤ .034). No other differences in osteochondral repair existed between subchondral drilling with 6 or 2 drill holes. Conclusion: Subchondral drilling independent of drill hole density significantly improves structural cartilage repair compared with sole defect debridement of full-thickness cartilage defects in sheep after 6 months. Subchondral drilling also leads to a better reconstitution of the subchondral bone compartment below the defects. Simultaneously, drilling reduced the formation of intralesional osteophytes caused by osseous overgrowth compared with debridement. Clinical Relevance: These results have important clinical implications, as they support subchondral drilling independent of drill hole number but discourage debridement alone for the treatment of small cartilage defects. Clinical studies are warranted to further quantify the effects of subchondral drilling in similar settings.