Microvascular Anatomy and Intrinsic Gene Expression of Menisci From Young Adults

Abstract

Background: Meniscal vascular supply is an important determinant of its healing potential. It has been reported that only the peripheral 30% of the meniscus is vascularized in cadavers aged 53 to 94 years; however, the vascularity in young patients, in whom meniscal repair is more often performed, is unknown. Purpose: The primary objective was to analyze and measure the microvascular anatomy of the meniscus in adult cadaveric specimens <35 years old. The secondary objective was to assess angiogenic potential by quantifying regional gene expression in a meniscal allograft cohort <45 years old. Study Design: Descriptive laboratory study. Methods: In part 1 of this study, 13 fresh-frozen cadaveric knees (age range, 22-34 years; mean, 28.5 years) underwent popliteal artery India ink injection and tissue clearing using a Spalteholz technique, followed by microvascular vascular measurement. In part 2, mRNA was isolated from 13 meniscal allografts (age range, 17-43 years; mean, 27.2 years), and expression of angiogenic genes, vascular endothelial growth factor ( VEGF), and vascular endothelial growth factor receptor 1 ( FLT1) was quantified using real-time polymerase chain reaction. Results: The maximal depth of vascular penetration into the periphery of the medial and lateral menisci ranged from 0% to 42% and 0% to 48%, respectively. There was variation in the degree of vascular penetration within the medial meniscus, with the posterior horn having a significantly smaller depth of penetration (median, 8.7%) than that of the anterior horn (median, 17.4%; P < .0001) or midbody (median, 17.5%; P = .0003). There were no differences in angiogenesis gene expression ( VEGF/ FLT1) based on circumferential or radial meniscal locations. Conclusion: The vascular supply of the medial and lateral menisci in specimens from adults <35 years of age extended farther than what was reported in specimens from older individuals; however, median values remained consistent. Gene expression of the angiogenic marker VEGF was low throughout all regions of uninjured menisci from young adults, which is consistent with reports in older specimens. Clinical Relevance: Improved understanding of meniscal vascular supply in young adults is critical to informing clinical treatment decisions.

Age-Related Changes in the Microvascular Density of the Human Meniscus

“…They reported that a perimeniscal capillary plexus originating in the capsular and synovial tissues of the joint supplies the peripheral 10% to 25% of the meniscus. A recent investigation by Crawford et al 7 confirmed these results in a younger age group. The authors used 13 cadaveric knee specimens with a mean age of 28.5 years (range, 22-34 years).…”

“…Fedje-Johnston et al 13 recently reported a higher cell density for the medial compared with the lateral meniscus in a cohort aged 1 month to 11 years. Crawford et al 7 could not detect a difference in vessel penetration between the medial and lateral meniscus. In our study, no differentiation between the medial and lateral meniscus was made.…”

Impediments to Meniscal Repair: Factors at Play Beyond Vascularity

“…For example, annulus fibrosus cells exhibit aberrant behavior, including fibrotic phenotypic changes (alphasmooth muscle actin expression) and even apoptosis, following removal of residual strains (Bonnevie et al, 2019). Similarly, transection of tendons (e.g., rotator cuff (Osti et al, 2017)) perpendicular to the aligned axis leads to similar fibrotic and apoptotic behavior (Egerbacher et al, 2008;Maeda et al, 2011;Lundgreen et al, 2013;T. et al, 2020).…”

“…Thus, the recent push to “save the meniscus” is complicated by the majority of tears occurring in either the red-white or white zones ( Terzidis et al, 2006 ), limiting repair potential with suturing. Further exacerbating this issue is that the posterior horn of the meniscus appears to be most injured ( Mansori et al, 2018 ; Jackson et al, 2019 ), yet exhibits the lowest vascular penetration ( Crawford et al, 2020 ).…”

A Classic Revisited

“…In this month’s journal, Crawford and colleagues 5 from the Steadman Philippon Research Institute in Vail, Colorado report on similar microvascular analysis of the human meniscus. They note that the Arnoczky and Warren study was performed on cadaveric specimens in the 6th through 10th decades of life, and their purpose was to provide a similar descriptive analysis in specimens aged under 35 years—the population in which a meniscus repair is most performed in clinical practice.…”