Peer Review #2 of "Improved cartilage regeneration by implantation of acellular biomaterials after bone marrow stimulation: a systematic review and meta-analysis of animal studies (v0.1)"

Bone marrow stimulation may be applied to regenerate focal cartilage defects, but generally results in transient clinical improvement and formation of fibrocartilage rather than hyaline cartilage. Tissue engineering and regenerative medicine strive to develop new solutions to regenerate hyaline cartilage tissue. This systematic review and meta-analysis provides a comprehensive overview of current literature and assesses the efficacy of articular cartilage regeneration by implantation of cell-laden versus cell-free biomaterials in the knee and ankle joint in animals after bone marrow stimulation. PubMed and EMBASE (via OvidSP) were systematically searched using tissue engineering, cartilage and animals search strategies. Included were primary studies in which cellular and acellular biomaterials were implanted after applying bone marrow stimulation in the knee or ankle joint in healthy animals. Study characteristics were tabulated and outcome data were collected for meta-analysis for studies applying semi-quantitative histology as outcome measure (117 studies). Cartilage regeneration was expressed on an absolute 0–100% scale and random effects meta-analyses were performed. Implantation of cellular biomaterials significantly improved cartilage regeneration by 18.6% compared to acellular biomaterials. No significant differences were found between biomaterials loaded with stem cells and those loaded with somatic cells. Culture conditions of cells did not affect cartilage regeneration. Cartilage formation was reduced with adipose-derived stem cells compared to other cell types, but still improved compared to acellular scaffolds. Assessment of the risk of bias was impaired due to incomplete reporting for most studies. Implantation of cellular biomaterials improves cartilage regeneration compared to acellular biomaterials.

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Prior Bone Marrow Stimulation Surgery Influences Outcomes After Cell-Based Cartilage Restoration: A Systematic Review and Meta-analysis

Orthopaedic Journal of Sports Medicine ◽

10.1177/23259671211035384 ◽

2021 ◽

Vol 9 (9) ◽

pp. 232596712110353

Author(s):

Charles J. Cogan ◽

James Friedman ◽

Jae You ◽

Alan L. Zhang ◽

Brian T. Feeley ◽

...

Keyword(s):

Systematic Review ◽

Bone Marrow ◽

Failure Rate ◽

Meta Analysis ◽

Failure Rates ◽

Bone Marrow Stimulation ◽

Marrow Stimulation ◽

Cartilage Restoration ◽

History Of ◽

The Mean

Background: Cell-based cartilage restoration with autologous chondrocyte implantation (ACI) is a safe and effective treatment for symptomatic cartilage lesions. Many patients undergoing ACI have a history of prior surgery, including bone marrow stimulation (BMS). There is mounting evidence that a history of prior BMS may impede healing of the ACI graft. Purpose/Hypothesis: The purpose of this study was to compare the failure rates of primary ACI with ACI after prior BMS. We hypothesized that ACI after BMS would have a significantly higher failure rate (defined as reoperation, conversion to arthroplasty, and/or imaging-based failure) compared with primary ACI. Study Design: Systematic review; Level of evidence, 4. Methods: A literature search was performed by use of PubMed and Embase databases for relevant articles published through October 2, 2020, to identify studies evaluating outcomes and failures rates of ACI after prior BMS in the knee. Results: Included were 11 studies comprising 1479 ACI procedures. The mean age at surgery ranged from 18.3 to 39.1 years, and the mean follow-up ranged from 3 to 20.6 years. All studies reported failure rates. The overall failure rate was significantly higher in the patients who underwent ACI after BMS, at 26.4% compared with 14.8% in the ACI group ( P < .001). Meta-analysis demonstrated an increased risk of failure in patients with a history of prior BMS (log odds ratio = –0.90 [95% confidence interval, –1.38 to –0.42]). Conclusion: This systematic review demonstrated that failure rates were significantly higher for patients treated with ACI after BMS relative to patients undergoing ACI without prior BMS. This finding has important implications when considering the use of BMS for defects that are amenable to cell-based restoration and when determining treatment options after failed BMS. Registration: PROSPERO (CRD42020180387).

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Bone marrow stimulation decreases retear rates after primary arthroscopic rotator cuff repair: a systematic review and meta-analysis

Journal of Shoulder and Elbow Surgery ◽

10.1016/j.jse.2018.11.049 ◽

2019 ◽

Vol 28 (4) ◽

pp. 782-791 ◽

Cited By ~ 5

Author(s):

Prabjit Ajrawat ◽

Tim Dwyer ◽

Mahmoud Almasri ◽

Christian Veillette ◽

Anthony Romeo ◽

...

Keyword(s):

Systematic Review ◽

Bone Marrow ◽

Rotator Cuff ◽

Rotator Cuff Repair ◽

Meta Analysis ◽

Arthroscopic Rotator Cuff Repair ◽

Bone Marrow Stimulation ◽

Marrow Stimulation ◽

Arthroscopic Rotator Cuff ◽

Cuff Repair

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The Subchondral Bone Is Affected by Bone Marrow Stimulation: A Systematic Review of Preclinical Animal Studies

Cartilage ◽

10.1177/1947603517711220 ◽

2017 ◽

Vol 10 (1) ◽

pp. 70-81 ◽

Cited By ~ 9

Author(s):

Dexter Seow ◽

Youichi Yasui ◽

Ian D. Hutchinson ◽

Eoghan T. Hurley ◽

Yoshiharu Shimozono ◽

...

Keyword(s):

Systematic Review ◽

Bone Marrow ◽

Articular Cartilage ◽

Bone Density ◽

Subchondral Bone ◽

Animal Studies ◽

Bone Marrow Stimulation ◽

Marrow Stimulation ◽

Chondral Defects ◽

Meta Analyses

Objective Despite the mechanical and biological roles of subchondral bone (SCB) in articular cartilage health, there remains no consensus on the postoperative morphological status of SCB following bone marrow stimulation (BMS). The purpose of this systematic review was to clarify the morphology of SCB following BMS in preclinical, translational animal models. Design The MEDLINE and EMBASE databases were systematically reviewed using specific search terms on April 19, 2016 based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The morphology of the SCB was assessed using of microcomputed tomography (bone density) and histology (microscopic architecture). Results Seventeen animal studies with 520 chondral lesions were included. The morphology of SCB did not recover following BMS. Compared with untreated chondral defects, BMS resulted in superior morphology of superficial SCB and cartilage but inferior morphology (specifically bone density, P < 0.05) of the deep SCB. Overall, the use of biological adjuvants during BMS resulted in the superior postoperative morphology of SCB. Conclusions Alterations in the SCB following BMS were confirmed. Biologics adjuvants may improve the postoperative morphology of both SCB and articular cartilage. Refinements of BMS techniques should incorporate consideration of SCB damage and restoration. Investigations to optimize BMS techniques incorporating both minimally invasive approaches and biologically augmented platforms are further warranted.

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