Osteochondral defects .pptx which is helpful

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1. JOURNAL CLUB BY DR RAMGOPAL SHARMA MODERATOR DR USMAN

2. INTRODUCTION Knee osteochondral lesions have always represented a problem because of the poor regeneration potential of cartilage. Traditionally autologous or allogenic osteochondral tissue transplantation was done to provide an immediate viable tissue . However these techniques demonstrated long term promising results , they also showed several drawbacks. Also chondrocyte based regenerative treatments developed to overcome these limitations , but didn’t provide optimal solution for osteochondral lesions.

3. Progress in the field of biomaterials has led to the development of various scaffolds to address the entire osteochondral unit. Multi layer cell free osteochondral scaffolds have been introduced with the aim to provide a biomimetic and biodegradable 3D structure that favours subchondral bone and cartilage like tissue regeneration. They showed potential to act as stimuli for differentiation of resident bone marrow stromal cells . Inducing an insitu tissue regeneration that allows a durable osteochondral tissue without need for cell augmentation.

4. However cell free multilayer scaffolds have currently been in trials and their results and effectiveness are still evaluated.

5. AIM : To review the available literature To analyse the clinical results

6. MATERIALS AND METHODS : A systematic review and meta analysis were performed on the literature of cell free osteochondral scaffold implantation for knee lesions. PUBMED WEB OF SCIENCE COCHRANE No time limitation No filters

7. INCLUSION CRITERION : CLINICAL STUDIES WRITTEN IN ENGLISH CELL FREE OSTEOCHONDRAL SCAFFOLDS FOR THE TREATMENT OF OSTEOCHONDRAL DEFECTS OF KNEE

8. EXCLUSION CRITERION : ARTICLES IN OTHER LANGUAGES PRE CLINICAL STUDIES STUDIES REPORTING OTHER PROCEDURES

9. For the included studies, relevant data year of publication, study design, number of patients evaluated, patient sex, age, and BMI, lesion size, lesion location, lesion grade, type of scaffold, scores reported, final follow-up, overall results were extracted from article texts, tables, and figures, are then collected . To assess the methodological quality of the collected data, the Coleman Methodology Score (CMS), modifed by Kon et  al to better suit the cartilage repair field, was determined for each study. Safety was evaluated through the reported adverse effects, while the failure rate was calculated through the documented surgical failures.

10. DISCUSSION The main finding of this study is that the available literature supports the use of multi-layer cell-free scaffolds for the treatment of patients with knee osteochondral defects. These scaffolds provided promising clinical improvement at short/mid-term follow-up, with a low rate of adverse events and an overall failure rate of 7.0% at a mean 31.0  months of follow-up. TruFit ® was the first one introduced in the clinical practice. It is a bilayer scaffold made of a semi porous poli -lactic (PLGA), poli -glycolic acid (PGA), and calcium sulfate biopolymer.

11. MaioRegen is the most widely studied multi-layer scaffold. It is a nanostructured implant consisting of different ratios of collagen and hydroxyapatite organized in 3 layers. The composition of this scaffold reproduces the extracellular matrix structures of cartilage and bone tissues and is based on the nucleation of hydroxyapatite nano crystals onto self-assembled collagen fibers to generate a chemically and morphologically graded biomimetic material.

12. Agili -C™ is the most recent osteochondral scaffold studied in the clinical practice. It is an aragonite-based scaffold consisting of two layers, a bone phase made of calcium carbonate in the aragonite crystalline form, and a superficial cartilage phase composed of modified aragonite and hyaluronic acid.

13. Studies investigating the safety and effectiveness of the TruFit ® implant often reported poor outcomes in terms of clinical results, failure rate, and histological evaluation. Dhollander et al documented a failure rate of 20% at 1 year of follow-up with the histological analysis showing fibrous vascularized repair tissue. Shivaji et al evaluated this scaffold also at long-term follow-up (121 months), reporting no statistically significant improvement in any score from baseline, while the MRI evaluation showed incomplete or no evidence of plug incorporation and persistent chondral loss. Based on these poor results, the TruFit ® scaffold has been withdrawn from the market

14. Regarding the scaffolds still available in the clinical practice, since the first trial published in 2011, numerous studies showed promising results in terms of safety profile and clinical improvement . In particular, this meta-analysis demonstrated that at 1-year follow-up the IKDC subjective score improved significantly compared with the baseline scores, demonstrating the efficacy of these techniques. Moreover, the evaluation at follow-up showed a further improvement from 1 to 3 years, suggesting that most of the benefit is achieved in the first year, but also that the osteochondral regeneration might need more time to reach stable results.

15. Still, despite the more complex lesion pattern due to the subchondral bone involvement, the osteochondral scaffolds provided a satisfactory clinical improvement. Unfortunately, the current literature does not allow to draw conclusions on the long-term results for osteochondral scaffolds, with no studies investigating the results over six years. Another important aspect evaluated in this study was the activity level. Sport represents a fundamental parameter to consider for cartilage lesions, especially in young and active patients .

16. The meta-analysis on the Tegner activity level documented a significant improvement from baseline to 1-year follow-up, With stable values at the at 2-year and at ≥3-year follow-up evaluations However, this meta-analysis reported a lower mean improvement of the Tegner score at 1- and 2-year follow-ups compared with the literature values offered by micro fracture, OAT and ACI procedures at the same follow-ups .

17. On one side, some studies described complete filling of the cartilage layer and a good integration of the graft, MRI evaluation demonstrated controversial and heterogeneous findings. Moreover, the maturation of the scaffold appeared slow, especially in the subchondral bone area, even though the majority of the studies highlighted a positive evolution over time.

18. Te systematic review and meta-analysis also underline the overall low-quality level of the studies in this Field, with only one RCT and three retrospective/prospective comparative studies. In a retrospective comparative study, Wang et  al. [74] compared the results of TruFit ® scaffold to micro fracture for the treatment of 132 patients with knee chondral or osteochondral defects. While no significant differences in clinical outcomes were reported up to 5  years, the scaffold group reported better activity level and MRI appearance of the defect, resulting in a more frequent good-quality tissue fill and cartilage isointensity .

19. In the only RCT available in this field, Kon et al evaluated 100 patients affected by symptomatic knee chondral and osteochondral lesions treated with MaioRegen or microfracture . While comparable results were found in the overall population, the osteochondral scaffold provided significantly better clinical results compared to microfracture in the treatment of deep osteochondral lesions and sport active patients at 2 years of follow-up. The authors concluded that microfracture technique can be considered a treatment option for purely chondral lesions, while offers worse results for osteochondral lesions, where osteochondral scaffolds showed to be a more suitable therapeutic solution.

20. Tis study presents some limitations, that reflect the weakness of the literature on the field. In fact, the lack of studies at long-term follow-up needs to be underlined, particularly given that the earliest scaffolds should have already reached a long-term follow-up with relatively numerous cohorts of patients. The overall quality level of the included studies is generally low, as confirmed by the low CMS and by the presence of only 1 RCT and 3 comparative studies.

21. Further high level studies with longer follow-up are needed, as well as comparative trials with the other osteochondral procedures including mosaicplasty and OCA, to clarify the potential and indication of these techniques to restore a functional osteochondral unit. Finally, while these cell-free scaffolds have been developed to overcome the problems related to cell-expansion, the possibility to augment them with cell concentrates, to exploit their regenerative and homeostatic potential in one-step procedures.

22. CONCLUSION The current literature suggested that multi-layer osteochondral scaffolds may provide clinical benefits for the treatment of knee osteochondral lesions at short- and mid-term follow-up and with a low number of failures, although the sport activity level obtained seems to be limited. Further research with high-level studies is needed to confirm the role of multi-layer scaffold for the treatment of osteochondral lesions of the knee .

23. CRITICAL APPRAISAL Title of the paper Multi layer cell free scaffold for osteochondral defects of knee Source Journal of experimental orthopaedics When was it published 2021 Authors of this paper Angelo boffa , L uca solaro , Luca andriolo et al

24. Did the study address relevant points ? Yes Was the study original? No Were the aims clearly stated? Yes Was the sample size justified? yes

25. Was power calculation performed? Yes Study design? Meta analysis Were the study groups comparable? Yes Was the assignment of patients to treatment randomised? no

26. Were the outcome measures stated were relevant? Yes Is there any missing data? No Were side effects and adverse effects documented? Yes

27. Were the aims of study fulfilled? Yes Are the conclusions of paper justified? Yes Is the paper relevant ? yes

28. INTRODUCTION Tissue engineering has emerged as an interesting alternative in regenerative medicine . Researchers have produced bioartificial substitutes by combining cells, biomaterials, and growth factors to restore the function of damaged organs. Tissue engineering is a multidisciplinary discipline that, through the rational combination of cells, biomaterials, and growth factors, allows the generation of bioartificial substitutes to repair, replace, or even increase the function of damaged tissues or organs.

29. At present, tissue engineering researchers are developing polymers and 3D bioartificial substitutes that accelerate the healing process with biomechanical behavior comparable to that of native tendons . This study presents a systematic review and meta-analysis of the existing progress in tissue engineering combining stem cells, growth factors, and scaffolds to assess the efficacy of treating tendon injuries in animal models . The objective of this study is to assess the efficacy of tissue engineering in treatment of tendon injuries.

30. MATERIALS AND METHODS: MEDLINE, Embase , and the Cochrane Library were searched for articles published between 1999 and 2016 about the use of tissue engineering in tendon injuries . The keywords used to conduct the research were “tendon injuries” and “tissue engineering”.

31. The studies were included if they investigated tissue engineering techniques for repairing a tendon lesion . Trials where required to have been conducted in animal models without restriction of species. The in vivo studies that investigated biomechanical or histological outcomes by tissue engineering strategies in injured tendons were also included . Due to the nature of intervention, it was agreed trials without blinding design.

32. We excluded duplicated studies, review articles, case reports, editorials and studies that were not published in English , And which were not reported as full-text articles , which were reported on a molecular or genetic level , which were reported without a control group

33. All analyses were performed using the RevMan software . Standard mean difference with 95% confidence interval (CI) was calculated. All the p-values were twosided ; statistical significance was defined as p<0.05.

34. DISCUSSSION Nowadays, an ideal engineered tendon substitute must be biodegradable, biocompatible, and biomechanically stable to support the tension during healing. Furthermore , the combination of biomaterials and cells must reassemble the native structure of tendon and support the regeneration without adhesions, toxicity, or, tissue rejection. Tissue engineering approaches to repair and improve tendon healing include: biological and decellularized tissues, the use of natural and synthetic biomaterials, the use of growth factors, stem cell-based therapies, or a combination of these strategies .

35. An example of a biologic scaffold is the use of porcine small intestinal submucosa . When this biomaterial is implanted, it induces a site-specific tissue repair with a tendon histologically similar to native tendon. However , the use of this scaffold may generate a foreign body and inflammatory reaction. Some authors are focused on the decellularization of tissues and organs in order to reduce the immunogenicity of these grafts, while maintaining the 3D structure and molecular composition of the extracellular matrix. In this sense, a reduction of the inflammatory response was observed in vivo.

36. Concerning the use of biomaterials, synthetic ones (such as polyglycolic acid) resulted in biomechanically and structurally stable tendon graft that supports tendon cell migration, especially those subjected to crosslinking . Similarly, chitosan-based hyaluronan hybrid fiber scaffolds have been used in tendon repair with better collagen type I production. Polyhydroxyalkanoates are a family of biopolymers with adaptable mechanical properties and delayed biodegradability .

37. Collagen type I, the main component of the tendon, has been shown to have an excellent biocompatibility and biodegradability; with nanostructured and crosslinking technologies, it is possible to polymerize the type I collagen to produce effective scaffolds. Electrospinning of collagen fibers produces elaborate nanofibers with the desirable size, density, and alignment.

38. Bone marrow and adipose mesenchymal stem cells (MSCs) are a commonly used cell source in musculoskeletal and peripheral nerve tissue engineering due to their ability to differentiate and their easy isolation and culture. When these cells were used in tendon repair, they improved tendinous healing in short-term studies . However, these studies suggest that no significant differences can be observed in long-term comparative studies; this could be related to the high regeneration capability of the animal models used.

39. Tendon-derived stem cells have higher mRNA expression of tenomodulin , scleraxis , type I collagen and decorin than that of MSCs, and could promote earlier and better tendon healing. On the other hand, in published studies, the biomechanical properties of the native tendon have never been restored successfully using tendon-derived stem cells. In addition to the regenerative potential of adipose-derived stromal cells, it was recently reported that these cells promote neo angiogenesis , cell proliferation and extracellular matrix (ECM) remodeling, and that they protect the regenerative microenvironment from macrophages.

40. This is the first study that showed favorable outcomes when using tissue engineering strategies in the treatment of tendon injuries in animal models. Therefore , the quality assessment score for most of the included studies was high, favoring the results of the meta-analysis. Nevertheless, there are a series of limitations associated with this work. First, like any systematic review, the conclusions of our work are affected by the quality of studies included . Second, our search strategy may associate search bias due to this is an English language-only revision, which entails language bias. On the other hand, the results on animal model have a limited value for a human application.

41. In recent years, thanks to tissue engineering techniques and the use of animal models, we have growth factors, scaffolds, and stem cells that can improve the histological and biomechanical characteristics of repair tissue, but do not fully recapitulate the native tendon.

42. CRITICAL APPRAISAL Title of the paper Tissue engineering strategies for the treatment of tendon injuries. Source Bone joint research , published in 2018 Authors D.GONALEZ I.MARTIN A.CAMPOS F.CAMPOS V.CARRIEL

43. Name of institution University of Granada , spain Did the study address relevant points ? Yes Was the study original ? No Were the aims clearly stated ? no

44. How were subjects recruited ? A meta analysis was done Was the sample size justified ? Not relevant Was a power calculation performed ? Yes Was the study design appropriate ? Meta analysis was done

45. Were the outcome measures stated and relevant? Yes Is there any missing data ? No Were the side effects documented ? Yes Was the duration and completeness of follow up appropriate? no

46. Were the sources of error discussed ? Yes Are the relevant findings justified? Yes Were the conclusions justified? Yes Are likely treatment benefits worth the harm? yes

47. Is the paper relevant ? yes

48. Journal clubs play an important role in the education of orthopedic residents. Their origin is typically attributed to Sir William Osler in the late 1870s. B y the 1980s have been used as a method for educating trainees and keeping physicians appraised of current peer reviewed research.

49. In 2000, Greene surveyed orthopedic chairmen and found that 99% of orthopedic residency programs held regular journal clubs, and that the primary goal of these clubs was to teach residents to evaluate scientific articles. The primary goal of this study was to identify the characteristics of an effective journal club as identified by orthopaedic residents and faculty. We also sought to compare the opinions of residents and faculty in order to identify areas of disagreement that may benefit from future research, discussion, and reconciliation . We also attempted to identify important goals of journal clubs in orthopedics

50. MATERIALS AND METHODS : One hundred and fifty-seven orthopedic residency programs with a contact e-mail address for either the program coordinator or program director were identified. A 15 question anonymous survey was distributed to faculty and residents at each program via the contact address listed. The survey was designed to determine the contribution of various journal club characteristics on the perceived effectiveness of journal club based on characteristics and club designs previously reported in the literature Most of the questions were multiple choice, and asked participants to select a single answer choice.

51. The survey remained open for a period of 2 months (May-June 2016), and responses were recorded electronically using Qualtrics survey software . For categorical data, a chi-square goodness-of-fit test was used to determine if responses differed significantly from an even distribution frequency. Resident and faculty responses were compared with a chi-square test of independence, and standardized residuals were calculated to determine the specific cells involved in differences that were identified . For ordinal data, a Mann-Whitney U test was used to compare resident and faculty responses.

52. Two hundred and four individuals responded to the survey . There were 106 resident/fellows and 98 faculty. The response rate per question decreased as the survey progressed as some participants ended the survey early. When asked to rank the goals of orthopedic journal clubs in order of importance, survey participants chose “teach the skillset of evaluating scientific papers” as the most important goal.

53. Participants felt that a leadership style with a faculty leader that rotated for each meeting was best, Monthly journal clubs were preferred and participants felt that the most effective presentation style was each article presented by a different resident . Participants felt that journal clubs should take place in the evening after daily activities and most felt that meetings should last 1 to 2 hours . The preference was to review 3 to 5 articles, include 8 to 15 participants , and discuss subspecialty topics rather than general orthopedics . A mandatory attendance policy was preferred . There was no strong preference with regard to the setting of the journal club .

54. “Participation and attendance” was ranked as the most important factor contributing to overall journal club effectiveness. . “Instill career-long habits of reading the orthopaedic literature among residents” was found to be significantly more important to faculty than residents. Faculty preferred to include the “most recent articles published in the last 1 to 2 months ”.

55. CONCLUSION This study surveyed orthopedic residents and faculty from departments around the United States to determine the goals of journal clubs at their institutions and to determine characteristics of clubs that effectively meet these goals . We found that participation and attendance and type and quality of articles were identified as the most important factors that contributed to effective journal clubs . A mandatory attendance policy and the inclusion of recent, clinically relevant papers, as well as classic articles that have influenced practice, were preferred.

56. Compared with faculty, residents favored holding journal club meetings outside of the hospital setting. The American Orthopedic Association (AOA) has developed a tool specifically designed to evaluate the effectiveness of journal clubs . It is meant for administration throughout the year and is essentially a self-assessment tool meant to track resident progress in 4 areas: ( 1) stimulate residents to read the current literature (2) increase resident knowledge of study design and statistics (3) ensure residents understand the hierarchy of evidence and (4) encourage residents to incorporate new knowledge and evidence into practice.

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