Enhancing Post-Expansion Chondrogenic Potential of Costochondral Cells in Self-Assembled Neocartilage

Murphy, Meghan K.; Huey, Daniel J.; Reimer, Andrew J.; Hu, Jerry C.; Athanasiou, Kyriacos A.

doi:10.1371/journal.pone.0056983

Cited by 30 publications

(46 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When chondrocytes were expanded with or without serum and then cultured in 3D (e.g., pellets, hydrogels, suspension cultures, etc.) in serum-free medium, the latter group expressed enhanced chondrogenic markers (160, 162, 164) and formed neocartilage with higher compressive properties (165). However, other studies have shown no difference in the type II collagen (165) and GAG (160) content of the neocartilage formed by chondrocytes expanded with or without serum.…”

Section: Tissue Engineering Strategies Used In Current Clinical Prmentioning

confidence: 99%

Cell-based tissue engineering strategies used in the clinical repair of articular cartilage

2016

Self Cite

View full text Add to dashboard Cite

One of the most important issues facing cartilage tissue engineering is the inability to move technologies into the clinic. Despite the multitude of review articles on the paradigm of biomaterials, signals, and cells, it is reported that 90% of new drugs that advance past animal studies fail clinical trials (1). The intent of this review is to provide readers with an understanding of the scientific details of tissue engineered cartilage products that have demonstrated a certain level of efficacy in humans, so that newer technologies may be developed upon this foundation. Compared to existing treatments, such as microfracture or autologous chondrocyte implantation, a tissue engineered product can potentially provide more consistent clinical results in forming hyaline repair tissue and in filling the entirety of the defect. The various tissue engineering strategies (e.g., cell expansion, scaffold material, media formulations, biomimetic stimuli, etc.) used in forming these products, as collected from published literature, company websites, and relevant patents, are critically discussed. The authors note that many details about these products remain proprietary, not all information is made public, and that advancements to the products are continuously made. Nevertheless, by fully understanding the design and production processes of these emerging technologies, one can gain tremendous insight into how to best use them and also how to design the next generation of tissue engineered cartilage products.

show abstract

Section: Tissue Engineering Strategies Used In Current Clinical Prmentioning

confidence: 99%

Cell-based tissue engineering strategies used in the clinical repair of articular cartilage

2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…36 Tensile mechanical properties were determined using the Test Resources 840L. 37 Briefly, 3 mm punches were used to trim construct samples and generate a dog-bone shape, which were glued to paper tabs to establish a gauge length of 1.45 mm. Samples were loaded at a constant rate of 1% strain per second.…”

Section: Compressive and Tensile Testingmentioning

confidence: 99%

Surface Zone Articular Chondrocytes Modulate the Bulk and Surface Mechanical Properties of the Tissue-Engineered Cartilage

Peng

McNary

Athanasiou³

et al. 2014

Tissue Engineering Part A

Self Cite

View full text Add to dashboard Cite

The central hypothesis of functional tissue engineering is that an engineered construct can serve as a viable replacement tissue in vivo by replicating the structure and function of native tissue. In the case of articular cartilage, this requires the reproduction of the bulk mechanical and surface lubrication properties of native hyaline cartilage. Cartilage tissue engineering has primarily focused on achieving the bulk mechanical properties of native cartilage such as the compressive aggregate modulus and tensile strength. A scaffold-free selfassembling process has been developed that produces engineered cartilage with compressive properties approaching native tissue levels. Thus, the next step in this process is to begin addressing the friction coefficient and wear properties of these engineered constructs. The superficial zone protein (SZP), also known as lubricin or PRG4, is a boundary mode lubricant that is synthesized by surface zone (SZ) articular chondrocytes. Under conditions of high loading and low sliding speeds, SZP reduces friction and wear at the articular surface. The objective of this investigation was to determine whether increasing the proportion of SZ chondrocytes in cartilage constructs, in the absence of external stimuli such as growth factors and mechanical loading, would enhance the secretion of SZP and improve their frictional properties. In this study, cartilage constructs were engineered through a self-assembling process with varying ratios of SZ and middle zone (MZ) chondrocytes (SZ:MZ): 0:100, 25:75, 50:50, 75:25, and 100:0. Constructs containing different ratios of SZ and MZ chondrocytes did not significantly differ in the glycosaminoglycan composition or compressive aggregate modulus. In contrast, tensile properties and collagen content were enhanced in nearly all constructs containing greater amounts of SZ chondrocytes. Increasing the proportion of SZ chondrocytes had the hypothesized effect of improving the synthesis and secretion of SZP. However, increasing the SZ chondrocyte fraction did not significantly reduce the friction coefficient. These results demonstrate that additional factors, such as SZPbinding macromolecules, surface roughness, and adhesion, need to be examined to modulate the lubrication properties of engineered cartilage.

show abstract

“…It was hypothesized that 1) in aggregates, increasing aggregate duration would increase type II to type I collagen ratio and GAG content, 2) in constructs, there is a beneficial aggregate culture duration that would increase overall collagen content, type II to type I collagen ratio, GAG content, and resulting mechanical properties, and 3) different types of cartilages may be obtained from differing aggregate durations. This work builds upon previous efforts to identify expansion conditions to enhance proliferation and maintain chondrogenic potential in third passage costochondral cells (34). The present study seeks to extend this effort by developing methods to manipulate the re-expression of the chondrogenic phenotype following monolayer.…”

Section: Introductionmentioning

confidence: 99%

Engineering a Fibrocartilage Spectrum through Modulation of Aggregate Redifferentiation

Murphy

Masters

et al. 2015

Cell Transplant

Self Cite

View full text Add to dashboard Cite

Expanded costochondral cells provide a clinically relevant cell source for engineering both fibrous and hyaline articular cartilage. Expanding chondrocytes in monolayer results in a shift toward a proliferative, fibroblastic phenotype. Three-dimensional aggregate culture may, however, be used to recover chondrogenic matrix production. This study sought to engineer a spectrum of fibrous to hyaline neocartilage from a single cell source by varying the duration of three-dimensional culture following expansion. In third passage porcine costochondral cells, the effects of aggregate culture duration were assessed after 0, 8, 11, 14, and 21 days of aggregate culture and after 4 subsequent weeks of neocartilage formation. Varying the duration of aggregate redifferentiation generated a spectrum of fibrous to hyaline neocartilage. Within 8 days of aggregation, proliferation ceased, and collagen and glycosaminoglycan production increased, compared with monolayer cells. In self-assembled neocartilage, type II to I collagen ratio increased with increasing aggregate duration, yet glycosaminoglycan content varied minimally. Notably, 14 days of aggregate redifferentiation increased collagen content by 25%, tensile modulus by over 110%, and compressive moduli by over 50%, compared with tissue formed in the absence of redifferentiation. A spectrum of fibrous to hyaline cartilage was generated using a single, clinically relevant cell source, improving the translational potential of engineered cartilage.

show abstract

Enhancing Post-Expansion Chondrogenic Potential of Costochondral Cells in Self-Assembled Neocartilage

Cited by 30 publications

References 51 publications

Cell-based tissue engineering strategies used in the clinical repair of articular cartilage

Cell-based tissue engineering strategies used in the clinical repair of articular cartilage

Surface Zone Articular Chondrocytes Modulate the Bulk and Surface Mechanical Properties of the Tissue-Engineered Cartilage

Engineering a Fibrocartilage Spectrum through Modulation of Aggregate Redifferentiation

Contact Info

Product

Resources

About