Strategies to minimize hypertrophy in cartilage engineering and regeneration

Abstract

Due to a blood supply shortage, articular cartilage has a limited capacity for self-healing once damaged. Articular chondrocytes, cartilage progenitor cells, embryonic stem cells, and mesenchymal stem cells are candidate cells for cartilage regeneration. Significant current attention is paid to improving chondrogenic differentiation capacity; unfortunately, the potential chondrogenic hypertrophy of differentiated cells is largely overlooked. Consequently, the engineered tissue is actually a transient cartilage rather than a permanent one. The development of hypertrophic cartilage ends with the onset of endochondral bone formation which has inferior mechanical properties. In this review, current strategies for inhibition of chondrogenic hypertrophy are comprehensively summarized; the impact of cell source options is discussed; and potential mechanisms underlying these strategies are also categorized. This paper aims to provide guidelines for the prevention of hypertrophy in the regeneration of cartilage tissue. This knowledge may also facilitate the retardation of osteophytes in the treatment of osteoarthritis.

Mandibular Condyle Repair after Partial Condylectomy in Patients with Active Condylar Hyperplasia

“…The condylar growth patterns in these types of procedures could contribute to a better understanding of regenerative processes since if a similar macromorphology is obtained between a treated condyle and a normal condyle, it is possible that a similar micromorphology is also obtained, including the presence of layers known to be in the normal condylar head. The resected condyle, initially with low vascularization, could lead to a secondary repair, considering that the development of hypertrophic cartilage in its final stage determines bone growth by endochondral methods with low mechanical resistance (Chen et al, 2015). In fact, during skeletogenesis in the embryological stage, the initial formation of basic cartilage is avascular at first; when the chondrocytes finalize their hypertrophic process, they are invaded by blood vessels (Maes, 2013), a condition that can be hypothesized in this case series.…”

Cell number and chondrogenesis in human mesenchymal stem cell aggregates is affected by the sulfation level of heparin used as a cell coating

“…11,41 This demonstrates that while many different platforms of MSC chondrogenesis exist, preventing hypertrophy remains a key challenge in cartilage tissue engineering, and additional culture methods, such as exposure to parathyroid hormones or co-culture with chondrocytes may be required to prevent hypertrophic differentiation during in vitro culture. 42–44 Although collagen X upregulation was measured in this MSC aggregate system, gene expression of other lineage markers, Runx2 (osteogenic), and PPARγ2 (adipogenic) were minimally changed or not expressed (data not shown), suggesting that those differentiation pathways were not favored in this system.…”

Chondrogenesis of human bone marrow mesenchymal stem cells in 3-dimensional, photocrosslinked hydrogel constructs: Effect of cell seeding density and material stiffness

“…Based on expression levels of hypertrophy related genes MMP13 and ColX (Figure 6) the new material PDLLA-PEG 1000 is not able to reduce hypertrophic response, an inevitable consequence of exposure to TGF-β3 containing chondroinductive medium. 47,48 However, it does offer the advantage of increased mechanical strength without a decrease in ECM production.…”