No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
A Biphasic Aragonite off the Shelf Implant for Articular Cartilage Restoration in Early OA
Abstract
Osteoarthritis (OA) refers to a group of mechanically induced joint disorders characterized by an epigenetic nature. It has been defined as a disease of the entire joint. Articular chondrocytes and subchondral osteocytes are constantly subject to stress, strain and load and, if homeostatic and reparative processes are unable to compensate for the destructive processes, the joint environment will suffer and present with structural damage and clinical symptoms.
The lack of drugs able to cure patients from OA has resulted in the use of intra-articular infiltrations and surgical procedures among which the implantation of biomimetic scaffolds. Biomimetic scaffolds are innovative materials created with the aim of encouraging bone and cartilage regeneration.
The latest generation of scaffolds have been developed with the aim of increasing the healing abilities of the human body's own cells and signaling factors to achieve superior tissue quality and better clinical outcomes.
The present paper presents the in vivo performance of biphasic aragonite scaffolds on knees affected by early OA. The implantation of bioscaffolds has been been evaluated with MRIs, KOOS scores at follow up and histologically.
The Agili-C scaffold's analysis has revealed it to be a viable option in the use of patients with mild to moderate OA
... The current finding of spectacularly high aragonite content in abalone could indicate a promising, high value utilisation of the investigated shells, particularly, for bone tissue engineering. Previous research has already demonstrated the osteogenic, osteoinductive and osteoconductive property of nacre in various in vitro and in vivo human and animal models [91][92][93][94] . Especially, favourable outcomes have been identified in human clinical trials. ...
... As well, purified aragonite obtained from corals has also been used to construct commercial medical implants such as Agili-c scaffold (CartiHeal). These implants have been shown to be a viable option for use in patients with mild to moderate osteoarthritis, and aligned, reported to improve patient outcomes 94,96 . ...
Molluscan shellfish aquaculture contributes to 42.6% of global aquaculture production. With a continued increase in shellfish production, disposal of shell waste during processing is emerging as an environmental and financial concern. Whilst major commercial species such as Crassostrea spp. has been extensively investigated on usage of its shell, with information that are crucial for valorisation, e.g. safety and crystal polymorphs, evaluated. There is currently little understanding of utilisation opportunities of shell in several uprising Australian commercially harvested species including Akoya Oyster (Pinctada fucata), Roe’s Abalone (Haliotis roei) and Greenlip Abalone (Haliotis levigata), making it challenging to identify ideal usages based on evidence-based information. Therefore, in this study, an interdisciplinary approach was employed to characterise the shells, and thereafter suggest some potential utilisation opportunities. This characterisation included crude mineral content, elemental profiling and food safety evaluation. As well, physical, chemical, and thermal stability of the shell products was assessed. TGA result suggests that all shells investigated have high thermal stability, suggesting the possibility of utilisation as a functional filler in engineering applications. Subsequent FTIR, SEM and XRD analyses identified that CaCO3 was the main compositions with up to 77.6% of it found to be aragonite. The spectacular high aragonite content compared to well-investigated Crassostrea spp. suggested an opportunity for the utilisation of refined abalone shell as a source of biomedical engineering due to its potent biocompatibility. Additionally, safety evaluations on whole shell also outlined that all investigated samples were safe when utilised as a crude calcium supplement for populations > 11 years old, which could be another viable options of utilisation. This article could underpin abalone and akoya industries actions to fully utilise existing waste streams to achieve a more sustainable future.
... In addition, another approved product, namely Agili-C made from coral composed of calcium carbonate, had been evaluated clinically and experiments confirmed positive results in terms of knee function and general physical abilities (Kon et al., 2022). A recent examination studied the capacity of this biphasic scaffold in patients with early osteoarthritis and the results of its implantation in the knees, introducing this scaffold as an option for mild to moderate osteoarthritis (Bertolino et al., 2022). Another study cleared incomplete regeneration with the MaioRegen scaffold by about 21.4% (Guérin and Pujol, 2020). ...
Approaches to the design and construction of biomimetic scaffolds for osteochondral tissue, show increasing advances. Considering the limitations of this tissue in terms of repair and regeneration, there is a need to develop appropriately designed scaffolds. A combination of biodegradable polymers especially natural polymers and bioactive ceramics, shows promise in this field. Due to the complicated architecture of this tissue, biphasic and multiphasic scaffolds containing two or more different layers, could mimic the physiology and function of this tissue with a higher degree of similarity. The purpose of this review article is to discuss the approaches focused on the application of biphasic scaffolds for osteochondral tissue engineering, common methods of combining layers and the ultimate consequences of their use in patients were discussed.
Articular cartilage lesions are a common injury that have become increasingly treatable with joint preservation procedures. Well-documented allograft and cellular treatments for these lesions are detailed elsewhere in this volume. This article discusses three new unique options for addressing these defects taking three different paths to address these complex injuries. Agili-C is an existing FDA- and EMEA-approved option using an acellular aragonite-based scaffold to treat both chondral and osteochondral lesions, with or without concurrent arthritis. Cartistem is a stem-cell-based product composed of culture-expanded allogeneic human umbilical cord blood-derived mesenchymal stem cells and hyaluronic acid hydrogel, which is in its final clinical trial stages in the United States, but already has regulatory approval in Korea. IMPACT and RECLAIM studies have shown the safety and efficacy of a new one-stage procedure utilizing autologous chondrons combined with allogeneic mesenchymal stem cells (MSCs) that can provide another effective single-stage treatment option.
Objective
To develop patient-focused consensus guidelines on the indications for the use of scaffolds to address chondral and osteochondral femoral condyle lesions.
Design
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.
Results
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.
Conclusions
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.
Background:
Autologous chondrocyte implantation (ACI) and microfracture are two of the main surgical treatment options for articular cartilage lesions of the knee. Consensus regarding the best clinical options to repair knee cartilage lesions is lacking. We undertook a systematic review to clarify the clinical efficacy of ACI and microfracture at minimum mean 5-year follow-up.
Methods:
A literature search was conducted using the MEDLINE, Embase and Cochrane Library databases up to August 2018. Only comparative clinical studies of ACI and microfracture for the treatment of articular cartilage lesions of the knee with level I/Ⅱ evidence were included. Clinical outcomes and the prevalence of treatment failure from each study were extracted and compared. The methodological quality of the included studies was analyzed by means of the PEDro scale.
Results:
Five comparative studies (three randomized controlled trials and two prospective cohort studies) met our eligibility criteria. ACI and microfracture elicited significant improvement in clinical outcomes after 5 years. However, better clinical results with significant differences were found with modified versions of ACI (ACI with a modified collagen membrane [ACI-C] or matrix-applied chondrocyte implantation [MACI]) than with microfracture as determined by the Knee Injury and Osteoarthritis Outcome Score, activities of daily living assessment, Tegner Activity Scale score, and the International Knee Documentation Committee objective and subjective scores. No significant difference was observed in the treatment failure rate between these two methods within a particular study.
Conclusions:
Currently, the best-available evidence suggests that some clinical outcomes of articular cartilage lesions of the knee treated with modified versions of ACI (ACI-C or MACI) can significantly improve patient outcomes at the mid-term follow-up of 5 years compared with those obtained using microfracture.
Osteoarthritis (OA) is a degenerative disease involving joint damage, an inadequate healing response and progressive deterioration of the joint architecture that commonly affects the knee and/or hip joints. It is a major world public health problem and is predicted to increase rapidly with an ageing population and escalating rate of obesity. Autologous blood-derived products possess much promise in the repair and regeneration of tissue and have important roles in inflammation, angiogenesis, cell migration and metabolism in pathological conditions, including OA. Utilising platelet-rich plasma (PRP) to treat tendon, ligament and skeletal muscle has shown variable results across many studies with the current evidence base for the efficacy of PRP in treating sports injuries remaining inconclusive. More uniformly positive results have been observed by various studies for PRP in OA knee in comparison to hyaluronic acid, other intra-articular injections and placebo than in other musculoskeletal tissue. However, methodological concerns as well as satisfactory PRP product classification prevent the true characterisation of this treatment. Thus, further research is required to investigate how leukocyte inclusion, activation and platelet concentration affect therapeutic efficacy. Furthermore, the optimisation of timing, dosage, volume, frequency and rehabilitation strategies need to be ascertained. For knee OA management, these concerns must be addressed before this promising treatment can be widely implemented.
The aim of this study is to investigate clinical and radiographic outcomes of a biomimetic scaffold for the treatment of osteochondral knee lesions in patients with early OA. Study population was represented by 26 patients with a mean age of 44 years affected by early OA. Inclusion criteria were two episodes of knee pain for more than 10 days in the last year, Kellgren-Lawrence OA grade 0 or I or II, and arthroscopic findings of cartilage defects. Nineteen patients had a previous surgery, 11 of which were revision surgeries of osteochondral unit. All patients were treated with a biomimetic scaffold with a tri-layered structure of type I equine collagen and magnesium-enriched hydroxyapatite. Clinical outcomes were evaluated using the IKDC, Lysholm, VAS, KOOS, and Tegner scores at baseline and at an average follow-up of 35 months. Magnetic resonance imaging (MRI) was performed at follow-up time in 19 patients. Clinical outcomes showed significant improvement in VAS, Lysholm, IKDC subjective score, and KOOS subscales in 69% of the patients. Complication rate of this cases series was 11%, with no surgical failure, although 31% of patients did not reach a significant improvement and were thus considered as clinical failure. MRI analysis showed integration of the scaffold only in 47% of the patients, with partial regeneration of the subchondral bone. No correlation between clinics and radiological images was found. The use of a biomimetic osteochondral scaffold in the setting of an early OA, alone or associated with other procedures, appeared to be a valid and safe option, able to provide good and stable clinical outcomes with high patient’s satisfaction and low complication rate.
Background
Symptomatic articular cartilage lesions of the knee are common and are being treated surgically with increasing frequency. While many studies have reported outcomes following a variety of cartilage restoration procedures, few have investigated outcomes of revision surgery after a failed attempt at cartilage repair or reconstruction.
Purpose
To investigate outcomes of revision cartilage restoration procedures for symptomatic articular cartilage lesions of the knee following a previously failed cartilage reconstructive procedure.
Study Design
Systematic review; Level of evidence, 4.
Methods
A literature search was performed by use of the PubMed, EMBASE, and MEDLINE/Ovid databases for relevant articles published between 1975 and 2017 that evaluated patients undergoing revision cartilage restoration procedure(s) and reported outcomes using validated outcome measures. For studies meeting inclusion criteria, relevant information was extracted.
Results
Ten studies met the inclusion criteria. Lesions most commonly occurred in the medial femoral condyle (MFC) (52.8%), with marrow stimulation techniques (MST) the index procedure most frequently performed (70.7%). Three studies demonstrated inferior outcomes of autologous chondrocyte implantation (ACI) following a previous failed cartilage procedure compared with primary ACI. One study comparing osteochondral allograft (OCA) transplant following failed microfracture (MFX) with primary OCA transplant demonstrated similar clinical outcomes and graft survival at midterm follow-up. No studies reported outcomes following osteochondral autograft transfer (OAT) or newer techniques.
Conclusion
This systematic review of the literature reporting outcomes following revision articular cartilage restoration procedures (most commonly involving the MFC) demonstrated a high proportion of patients who underwent prior MST. Evidence is sufficient to suggest that caution should be taken in performing ACI in the setting of prior MST, likely secondary to subchondral bone compromise. OCA appears to be a good revision treatment option even if the subchondral bone has been violated from prior surgery or fracture.
Purpose:
To compare the clinical outcomes of osteoarthritis indices (WOMAC and Lequesne scores) and adverse events in the treatment of osteoarthritis (OA) of the knee with platelet-rich plasma (PRP) versus hyaluronic acid (HA) or placebo.
Methods:
A systematic review and meta-regression were performed to compare outcomes between PRP injections versus HA or placebo. Relevant randomized control trials were identified from Medline and Scopus from date of inception to 13 August 2015.
Results:
Nine of 551 studies were eligible; 6, 5, 5, 5, 2, 2, 2 and 7 studies were included in pooling of WOMAC total, pain, stiffness and function scores, Lequesne score, IKDC score, EQ-VAS score and adverse events in OA knee patients, respectively. The PRP injections had -15.4 (95 % CI -28.6, -2.3, p = 0.021), lower mean WOMAC total scores, and 8.83 (95 % CI 5.88, 11.78, p < 0.001), 7.37 (95 % CI 4.33, 10.05, p = 0.021) higher mean IKDC and EQ-VAS scores when compared to HA injections. However, PRP injections had no significant differences in WOMAC pain, stiffness and function scores, as well as Lequesne score and adverse events when compared to HA or placebo.
Conclusion:
In short-term outcomes (≤1 year), PRP injection has improved functional outcomes (WOMAC total scores, IKDC score and EQ-VAS) when compared to HA and placebo, but has no statistically significant difference in adverse events when compared to HA and placebo. This study suggests that PRP injection is more efficacious than HA injection and placebo in reducing symptoms and improving function and quality of life. It has the potential to be the treatment of choice in patients with mild-to-moderate OA of the knee who have not responded to conventional treatment.
Level of evidence:
I.
With the emerging interest in regenerative medicine and tissue engineering, new treatment modalities being developed for joint disorders including joint surface lesions and articular cartilage defects. The clinical outcome of these novel approaches appears rather unpredictable and is due to many reasons but definitely also linked to the patient profile. As a typical example, symptomatic articular cartilage lesions can be presented in an otherwise normal joint, or associated with several other joint tissue alterations including meniscal lesions and abnormalities of the underlying bone. The outcome of novel treatments may well be influenced by the status of the whole joint, and the potential to develop osteoarthritis. To better identify the patients at risk and responders to certain treatments, it is of use to define and most importantly classify patients with "early osteoarthritis". Here, classification criteria for this group of patients are presented, allowing a more defined and accurate inclusion in clinical trials in the future.
As the understanding of interactions between articular cartilage and subchondral bone continues to evolve, increased attention is being directed at treatment options for the entire osteochondral unit, rather than focusing on the articular surface only. It is becoming apparent that without support from an intact subchondral bed, any treatment of the surface chondral lesion is likely to fail. This article reviews issues affecting the entire osteochondral unit, such as subchondral changes after marrow-stimulation techniques and meniscectomy or large osteochondral defects created by prosthetic resurfacing techniques. Also discussed are surgical techniques designed to address these issues, including the use of osteochondral allografts, autologous bone grafting, next generation cell-based implants, as well as strategies after failed subchondral repair and problems specific to the ankle joint. Lastly, since this area remains in constant evolution, the requirements for prospective studies needed to evaluate these emerging technologies will be reviewed.
Second-generation autologous chondrocyte implantation with scaffolds stabilizing the grafts is a clinically effective procedure for cartilage repair. In this ongoing prospective observational case report study, we evaluated the effectiveness of BioSeed-C, a cell-based cartilage graft based on autologous chondrocytes embedded in fibrin and a stable resorbable polymer scaffold, for the treatment of clinical symptomatic focal degenerative defects of the knee.
Clinical outcome after 4-year clinical follow-up was assessed in 19 patients with preoperatively radiologically confirmed osteoarthritis and a Kellgren-Lawrence score of 2 or more. Clinical scoring was performed before implantation of the graft and 6, 12, and 48 months after implantation using the Lysholm score, the Knee injury and Osteoarthritis Outcome Score (KOOS), the International Knee Documentation Committee (IKDC) score, and the International Cartilage Repair Society (ICRS) score. Cartilage regeneration and articular resurfacing were assessed by magnetic resonance imaging (MRI) 4 years after implantation of the autologous cartilage graft.
Significant improvement (P < 0.05) of the Lysholm and ICRS scores was observed as early as 6 months after implantation of BioSeed-C and remained stable during follow-up. The IKDC score showed significant improvement compared with the preoperative situation at 12 and 48 months (P < 0.05). The KOOS showed significant improvement in the subclasses pain, activities of daily living, and knee-related quality of life 6 months as well as 1 and 4 years after implantation of BioSeed-C in osteoarthritic defects (P < 0.05). MRI analysis showed moderate to complete defect filling with a normal to incidentally hyperintense signal in 16 out of 19 patients treated with BioSeed-C. Two patients without improvement in the clinical and MRI scores received a total knee endoprosthesis after 4 years.
The results show that the good clinical outcome achieved 1 year after implantation of BioSeed-C remains stable over the course of a period of 4 years and suggest that implanting BioSeed-C is a promising treatment option for the repair of focal degenerative defects of the knee.
The efficacy of arthroscopic surgery for the treatment of osteoarthritis of the knee is unknown.
We conducted a single-center, randomized, controlled trial of arthroscopic surgery in patients with moderate-to-severe osteoarthritis of the knee. Patients were randomly assigned to surgical lavage and arthroscopic débridement together with optimized physical and medical therapy or to treatment with physical and medical therapy alone. The primary outcome was the total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score (range, 0 to 2400; higher scores indicate more severe symptoms) at 2 years of follow-up. Secondary outcomes included the Short Form-36 (SF-36) Physical Component Summary score (range, 0 to 100; higher scores indicate better quality of life).
Of the 92 patients assigned to surgery, 6 did not undergo surgery. Of the 86 patients assigned to control treatment, all received only physical and medical therapy. After 2 years, the mean (+/-SD) WOMAC score for the surgery group was 874+/-624, as compared with 897+/-583 for the control group (absolute difference [surgery-group score minus control-group score], -23+/-605; 95% confidence interval [CI], -208 to 161; P=0.22 after adjustment for baseline score and grade of severity). The SF-36 Physical Component Summary scores were 37.0+/-11.4 and 37.2+/-10.6, respectively (absolute difference, -0.2+/-11.1; 95% CI, -3.6 to 3.2; P=0.93). Analyses of WOMAC scores at interim visits and other secondary outcomes also failed to show superiority of surgery.
Arthroscopic surgery for osteoarthritis of the knee provides no additional benefit to optimized physical and medical therapy. (ClinicalTrials.gov number, NCT00158431.)
Many patients report symptomatic relief after undergoing arthroscopy of the knee for osteoarthritis, but it is unclear how the procedure achieves this result. We conducted a randomized, placebo-controlled trial to evaluate the efficacy of arthroscopy for osteoarthritis of the knee.
A total of 180 patients with osteoarthritis of the knee were randomly assigned to receive arthroscopic débridement, arthroscopic lavage, or placebo surgery. Patients in the placebo group received skin incisions and underwent a simulated débridement without insertion of the arthroscope. Patients and assessors of outcome were blinded to the treatment-group assignment. Outcomes were assessed at multiple points over a 24-month period with the use of five self-reported scores--three on scales for pain and two on scales for function--and one objective test of walking and stair climbing. A total of 165 patients completed the trial.
At no point did either of the intervention groups report less pain or better function than the placebo group. For example, mean (+/-SD) scores on the Knee-Specific Pain Scale (range, 0 to 100, with higher scores indicating more severe pain) were similar in the placebo, lavage, and débridement groups: 48.9+/-21.9, 54.8+/-19.8, and 51.7+/-22.4, respectively, at one year (P=0.14 for the comparison between placebo and lavage; P=0.51 for the comparison between placebo and débridement) and 51.6+/-23.7, 53.7+/-23.7, and 51.4+/-23.2, respectively, at two years (P=0.64 and P=0.96, respectively). Furthermore, the 95 percent confidence intervals for the differences between the placebo group and the intervention groups exclude any clinically meaningful difference.
In this controlled trial involving patients with osteoarthritis of the knee, the outcomes after arthroscopic lavage or arthroscopic débridement were no better than those after a placebo procedure.
The discrepancy between successful experimental studies of cartilage repair and the clinical results is unexplained. We have evaluated the effect of metabolic alterations in joint homeostasis owing to an articular defect on the outcome of cartilage repair using tissue engineering methods. We used 21 adolescent Dutch goats divided into three groups. The control knees were left untreated while the contralateral knee was randomised to receive either no treatment (N), early treatment (E) or late treatment (L). The metabolism of proteoglycans in the surrounding joint surface was determined and correlated with the O'Driscoll score used to quantify the histological aspect of the repair of the defect. Synthesis of proteoglycan (PG) was increased in all groups. The release of glucosaminoglycan (GAG) was significantly higher in the untreated but not after early transplantation (1.3 v 1.8 NS). The cartilage repair scores in the early treatment group were not as good as those of the normal control group, but were significantly better when compared with both the untreated defects and the late treated defects. Defects which had been treated late showed a significantly decreased score when compared with those which had had early treatment or the normal control group and did not differ (p = 0.12) from those with no treatment. The histological and biochemical scores closely resembled the macroscopic and functional parameters which showed a significant deterioration for the late treated group and those without treatment compared with animals treated early. Thus, tissue-engineered cartilage repair is negatively influenced by altered matrix metabolism. Early treatment showed significantly better results for repair of cartilage than late or no treatment, with a concurrent decrease in the detrimental disturbance of cartilage metabolism which constituted a protective effect on the articulation.
Background
Osteoarthritis (OA) is considered a contraindication to most cartilage repair techniques. Several regenerative approaches have been attempted with the aim of delaying or preventing joint replacement, with controversial results. Currently, there is a paucity of data on the use of single-step techniques, such as cell-free biomimetic scaffolds, for the treatment of joint surface lesions (JSLs) in OA knees.
Purpose
To present the 2-year follow-up clinical and radiological outcomes after implantation of a novel, cell-free aragonite-based scaffold for the treatment of JSLs in patients with mild to moderate knee OA in a multicenter prospective study.
Study Design
Case series; Level of evidence, 4.
Methods
A total of 86 patients, 60 male and 26 female, with a mean age of 37.4 ± 10.0 years, mild to moderate knee OA, and a mean defect size of 3.0 ± 1.7 cm ² , were recruited at 8 medical centers according to the following criteria: radiographic mild to moderate knee OA (Kellgren-Lawrence grade 2 or 3); up to 3 treatable chondral/osteochondral defects (International Cartilage Repair Society grades 3 and 4) on the femoral condyles or trochlea; a total defect size ≤7 cm ² ; and no concurrent knee instability, severe axial malalignment, or systemic arthropathy. All patients were evaluated at baseline and at 6, 12, 18, and 24 months after implantation using the Knee injury and Osteoarthritis Outcome Score (KOOS) and International Knee Documentation Committee (IKDC) subjective score. Additionally, magnetic resonance imaging (MRI) was performed to assess the amount of cartilage defect filling at the repaired site.
Results
Significant improvement on all KOOS subscales was recorded from baseline (Pain: 49.6 ± 13.1; Activities of Daily Living [ADL]: 56.1 ± 18.4; Sport: 22.8 ± 18.8; Quality of Life [QoL]: 23.5 ± 16.5; Symptoms: 55.4 ± 19.9) to the 24 months’ follow-up (Pain: 79.5 ± 21.1 [ P < .001]; ADL: 84.1 ± 21.4 [ P < .001]; Sport: 60.8 ± 31.9 [ P < .001]; QoL: 54.9 ± 30.4 [ P < .001]; Symptoms: 77.7 ± 21.2 [ P < .001]). The IKDC subjective score showed a similar trend and improved from 37.8 ± 14.7 at baseline to 65.8 ± 23.5 at 24 months ( P < .001). MRI showed a significant increase in defect filling over time: up to 78.7% ± 25.3% of surface coverage after 24 months. Treatment failure requiring revision surgery occurred in 8 patients (9.3%).
Conclusion
The use of an aragonite-based osteochondral scaffold in patients with JSLs and mild to moderate knee OA provided significant clinical improvement at the 24-month follow-up, as reported by the patients. These findings were associated with good cartilage defect filling, as observed on MRI.
Background:
Chondral and osteochondral lesions in osteoarthritic knees of young patients remain challenging for orthopaedic surgeons, due to a combination of high functional demands and limited indications for joint replacement in this population. The possibility of extending the indication of cartilage regenerative procedures to these patients may allow the delay of metal resurfacing.
Purpose:
To analyze the potential of a cartilage regenerative approach to provide clinical benefits in young patients with osteoarthritic knees, documenting outcomes in terms of clinical improvement as well as failures, in particular regarding knee replacement, at long-term follow-up.
Study design:
Case series; Level of evidence, 4.
Methods:
A total of 41 patients (mean ± SD age, 43 ± 9 years) who had cartilage lesions (4 ± 2 cm2) in osteoarthritic knees (Kellgren-Lawrence grade 2 or 3) underwent matrix-assisted autologous chondrocyte transplantation (MACT) as a salvage procedure. Patients were evaluated with International Knee Documentation Committee (IKDC), EuroQol visual analog scale (EQ-VAS), and Tegner scores before surgery; at 1, 2, 5, and 9 years after surgery; and at a final follow-up at a mean of 15 years after surgery (range, 14-18 years). Failures were also recorded.
Results:
An improvement was observed in all scores after surgery, but a progressive worsening over time was noted. The mean ± SD IKDC score improved from 38.6 ± 16.2 to a maximum of 66.0 ± 18.6 at 2 years (P < .0005), with a subsequent deterioration until the final evaluation at 56.2 ± 21.7 (P = .024). A similar trend was confirmed by EQ-VAS scores. Tegner scores improved at all follow-up points but did not reach the preinjury level. Patients who underwent combined surgery obtained significantly lower results. Only 13 patients (32%) had an IKDC score higher than 70. During the follow-up period, 21 patients underwent reoperation (18 with knee replacement) and 3 more patients experienced clinical failure, for a total surgical and clinical failure rate of 59% at 15 years.
Conclusion:
The use of cartilage regenerative surgical procedures, such as MACT, as salvage procedures for young, active patients affected by chondral and osteochondral lesions in osteoarthritic knees led to a limited improvement, with the majority of patients experiencing failure at long-term follow-up. Although a minor subpopulation experienced favorable and stable improvement, the use of MACT for such a challenging indication remains questionable until responding patients can be profiled.
Osteoarthritis is a common condition that affects many individuals resulting in pain, reduced mobility, and decreased function. Corticosteroids have been a mainstay of osteoarthritis treatment. Studies have shown that they provide short-term pain improvement and can be used for osteoarthritis flares. Hyaluronic acid injections have extensively been studied in knee osteoarthritis but to a lesser degree in other joints. Despite some debate between societies, a large number of recent studies have shown hyaluronic acid to be a viable treatment option showing longer-term improvement in both pain and function.
Purpose:
"Early Osteoarthritis (EOA)" has been defined combining clinical, imaging and surgical parameters, with the aim to identify patients in early degenerative phases, who might benefit from the use of available regenerative procedures. Aim of this first clinical trial is to prospectively evaluate the results obtained in a group of patients meeting the inclusion criteria of "EOA" as proposed by the ESSKA Cartilage Committee, and surgically treated with the implantation of a multi-phasic osteochondral scaffold.
Methods:
23 patients were prospectively evaluated at 12 and 24 months of follow-up. Etiology of the chondral or osteochondral defect was rated as microtraumatic or degenerative in 18 cases, and traumatic in 5 cases. Patients included were complaining of clinical symptoms like knee pain and affected by chondral and osteochondral lesions located at the femoral condyles or trochlea and MRI findings demonstrating articular cartilage degeneration and/or meniscal degeneration and/or subchondral bone marrow lesions.
Results:
All patients increased significantly in any clinical score adopted. The IKDC subjective score increased from 42.8 ± 13.8 at basal evaluation to 74.3 ± 17.4 at 12 months' (p < 0.0005), being stable (74.9 ± 20.4) up to the final follow-up of 24 months. Tegner score showed a statistically significant improvement in sports activity from 3.3 ± 2.7 pre-operative to 4.6 ± 2.2 at 12 months (p < 0.005), with a slight improvement to the final evaluation (4.7 ± 2.1; n.s.). However, the activity level was significantly lower than the pre-injury one (6.1 ± 2.6; p = 0.004). A significant difference was shown between patients younger versus older than 40 years, with younger patients had better clinical improvement (76.0 ± 18.6 vs 45.1 ± 38.8 respectively, p = 0.037).
Conclusions:
The implantation of a multi-phasic osteochondral scaffold represents a good option after failure of conservative management for Early OA patients, where younger age represent an important factor for a better outcome. Longer follow-up is needed to evaluate the benefit over time.
Level of evidence:
IV, case series.
Background:
Young patients with osteoarthritic knees are a challenging population because of a combination of high functional demands and limited indication for joint replacement.
Purpose:
To analyze the potential of the cartilage regenerative approach by documenting the results and failures of matrix-assisted autologous chondrocyte transplantation (MACT) at midterm follow-up.
Study design:
Case series; Level of evidence, 4.
Methods:
Forty-four patients affected by cartilage lesions in osteoarthritic knees underwent MACT as a salvage procedure. The mean age at surgery was 42 years (range, 20-58 years), and the average defect size was 4 cm(2) (range, 1.5-9 cm(2)). Patients were prospectively evaluated with the subjective International Knee Documentation Committee (IKDC), EuroQol visual analog scale (EQ-VAS), and Tegner scores preoperatively; at 1, 2, and 5 years; and at a final assessment at 9 years' mean follow-up. Adverse events and failures were also reported.
Results:
A statistically significant improvement was observed in all scores from the initial evaluation to the final follow-up. The mean ± standard deviation IKDC subjective score improved from 38.0 ± 15.8 to 67.0 ± 18.3 at 2 years (P < .0005), with a subsequent decrease to 57.8 ± 20.6 at the final follow-up (P = .012). The same trend was confirmed by the EQ-VAS score. The activity level revealed by the Tegner score improved at all follow-ups but without achieving the preinjury level. The analysis of the influencing factors showed the importance of the meniscus condition, revealing a significantly inferior outcome in knees with previous or combined partial meniscectomy procedures. During the study period, 12 patients had failed results, producing a cumulative failure rate of 27.3%. At the last evaluation, half of the patients considered their condition not better than before the treatment, and 39% would not repeat the treatment considering the results obtained.
Conclusion:
Despite a statistically significant improvement, the clinical outcome was poor. A higher improvement could be obtained in patients who had not undergone previous or combined meniscectomies, but this was limited over time. The failure rate was also high, regardless of the degree of osteoarthritis. Tissue-engineered cartilage implantation is questionable for this indication, and the limits of this scaffold-based procedure have to be considered if it is used as a salvage procedure for young patients affected by knee osteoarthritis.
In the last decade, huge steps forward have been made in the field of cartilage regeneration. The most recent trend for treating chondral/osteochondral lesions is based on the application of smart biomaterials that could lead to "in situ" regeneration of not only cartilage, but also subchondral bone, preferably through a single step procedure to reduce the costs and the morbidity for the patient. This innovative approach is currently under investigation as several "scaffolds" have been proposed in clinical practice, with or without the aid of cells, with the opportunity, in the second case, of bypassing the strict limits imposed by cell manipulation regulations. Furthermore, the fascinating potential of mesenchymal stem cells has recently opened new paths of research to discover how and whether these powerful entities can really contribute to tissue regeneration. The first clinical trials have been published but further high quality research is needed to understand their mechanisms of action, their limits, and their clinical efficacy.
Osteoarthritis (OA) refers to a group of mechanically-induced joint disorders to which both genetic and acquired factors contribute. Current pathophysiological concepts focus on OA as a disease of the whole joint. Within these models, the functional unit formed by the articular cartilage and the subchondral bone seems to be of particular interest. Cartilage and bone receive and dissipate the stress associated with movement and loading, and are therefore continuously challenged biomechanically. Recent data support the view that cartilage and bone can communicate over the calcified tissue barrier; vessels reach out from bone into the cartilage zone, patches of uncalcified cartilage are in contact with bone, and microcracks and fissures further facilitate transfer of molecules. Several molecular signaling pathways such as bone morphogenetic proteins and Wnts are hypothesized to have a role in OA and can activate cellular and molecular processes in both cartilage and bone cells. In addition, intracellular activation of different kinase cascades seems to be involved in the molecular crosstalk between cartilage and bone cells. Further research is required to integrate these different elements into a comprehensive approach that will increase our understanding of the disease processes in OA, and that could lead to the development of specific therapeutics or treatment strategies.
Young patients with early osteoarthritis wishing to remain functionally active have limited treatment options. Existing studies examining the use of autologous chondrocyte implantation (ACI) have included patients with early degenerative changes; however, none specifically investigated the outcome of ACI with this challenging problem. We prospectively followed 153 patients (155 knees) for up to 11 years after treatment with ACI for early-stage osteoarthritis. Patient pain and function was assessed using WOMAC, modified Cincinnati, SF-36, Knee Society score, and a satisfaction questionnaire. Mean patient age was 38.3 years. On average, 2.1 defects were treated per knee; the mean defect size was 4.9 cm2 and total area per knee was 10.4 cm2. Eight percent of joints were considered treatment failures that went on to arthroplasty and the remaining patients experienced 50% to 75% improvement in WOMAC subscales. Our data suggest that ACI in patients with early osteoarthritis results in clinically relevant reductions in pain and improvement in function. At 5 years postoperatively, 92% of patients were functioning well and were able to delay the need for joint replacement. Given the limited number of treatment options for this subset of patients, autologous chondrocyte implantation may offer improved quality of life for young osteoarthritic patients.
Level of Evidence: Level IV, case series. See Guidelines for Authors for a complete description of levels of evidence.
Despite the lack of consensus guidelines and randomized control trials, the use of arthroscopy for the treatment of osteoarthritis of the knee has increased over the last decade. Techniques used for the arthroscopic treatment of osteoarthritis of the knee include joint lavage, joint débridement, meniscectomy, abrasion arthroplasty, and microfracture. We performed a retrospective, evidence-based review of the current literature on the arthroscopic treatment of osteoarthritis of the knee and provide insight into the study design flaws and difficulties associated with the current research on this controversial topic. Our literature search yielded 18 relevant studies. Of these, one was Level I evidence, five were Level II, six were Level III, and six were Level IV. We found limited evidence-based research to support the use of arthroscopy as a treatment method for osteoarthritis of the knee. Arthroscopic débridement of meniscus tears and knees with low-grade osteoarthritis may have some utility, but it should not be used as a routine treatment for all patients with knee osteoarthritis.
Natural coral exoskeleton as a bone graft substitute: A review
- Demers
Importance of surgical cartilage therapy in early arthrosis
- Feucht