Tissue engineering of stratified articular cartilage from chondrocyte subpopulations

Klein, Travis J.; Schumacher, Barbara L.; Schmidt, Tannin A.; Li, K.; Voegtline, Michael S.; Masuda, Koichi; Thonar, Eugene J.‐M.A.; Sah, Robert L.

doi:10.1016/s1063-4584(03)00090-6

Cited by 199 publications

(152 citation statements)

References 40 publications

(51 reference statements)

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“…The biochemical content of the shaped constructs in this study is consistent with previously described constructs [26,29,38]. Like many tissue-engineered cartilaginous constructs, the constructs here had lower extracellular matrix content, especially collagen, compared to that of native cartilage.…”

Section: Discussionsupporting

confidence: 87%

“…Previously, stratified cartilaginous constructs with S chondrocytes atop M chondrocytes maintain the zonal characteristics typical of their source, such as proteoglycan 4 and differential matrix production [26,36]. Such differential spatial characteristics result in inhomogeneous biochemical and biomechanical properties of native cartilage with respect to depth and may be important in the maturation and, ultimately, function of tissue-engineered cartilaginous constructs as well [24].…”

Section: Discussionmentioning

confidence: 99%

“…Cartilaginous constructs have been created with stratification of superficial and middle/deep zone subpopulations [26,36] and with deep zone layer and calcified cartilage layer [2]. Such constructs maintain the zonal-specific characteristics, including the synthesis and secretion of proteoglycan 4 by the chondrocytes derived from the superficial zone [26], relatively high levels of matrix production by deep zone chondrocytes [36], and mineralization in the calcified cartilage layer [2]. This structural organization may be important since various cellular products are correlated with inhomogeneous biochemical and mechanical properties of articular cartilage [28].…”

Section: Introductionmentioning

confidence: 99%

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Shaped, Stratified, Scaffold-free Grafts for Articular Cartilage Defects

Han

Bae

Hsieh-Bonassera

et al. 2008

Clin Orthop Relat Res

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One goal of treatment for large articular cartilage defects is to restore the anatomic contour of the joint with tissue having a structure similar to native cartilage. Shaped and stratified cartilaginous tissue may be fabricated into a suitable graft to achieve such restoration. We asked if scaffold-free cartilaginous constructs, anatomically shaped and targeting spherically-shaped hips, can be created using a molding technique and if biomimetic stratification of the shaped constructs can be achieved with appropriate superficial and middle/deep zone chondrocyte subpopulations. The shaped, scaffold-free constructs were formed from the alginate-released bovine calf chondrocytes with shaping on one (saucer), two (cup), or neither (disk) surfaces. The saucer and cup constructs had shapes distinguishable quantitatively (radius of curvature of 5.5 ± 0.1 mm for saucer and 2.8 ± 0.1 mm for cup) and had no adverse effects on the glycosaminoglycan and collagen contents and their distribution in the constructs as assessed by biochemical assays and histology, respectively. Biomimetic stratification of chondrocyte subpopulations in saucer-and cup-shaped constructs was confirmed and quantified using fluorescence microscopy and image analysis. This shaping method, combined with biomimetic stratification, has the potential to create anatomically contoured large cartilaginous constructs.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Shaped, Stratified, Scaffold-free Grafts for Articular Cartilage Defects

Han

Bae

Hsieh-Bonassera

et al. 2008

Clin Orthop Relat Res

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“…The disks were cut either to include the superficial zone and the intact articular surface (superficial, 0-0.4 mm from articular surface) or from the middle zone (middle, 0.4-0.8 mm from articular surface). 22 Synovial Fluid/Purified PRG4 Synovial fluid was obtained from bovine joints, and its PRG4 content was determined to be 450 mg/mL by Western blot with Image Quant 5.2 software, comparing the intensity of the 345 kDa band of SF with those of PRG4 standards purified from cartilage culture medium by isopyknic CsCl density-gradient ultracentrifugation and ion-exchange chromatography and quantified based on protein content, as described previously. 23 For purified PRG4, cartilage disks were harvested as described above from the superficial zone of immature (1-to 3-week-old) bovines and cultured in medium (lowglucose Dulbecco's modified Eagle's medium (DMEM), 10 mM HEPES buffer, 0.1 mM nonessential amino acids, 0.4 mM L-proline, 2 mM L-glutamine, 100 U/mL penicillin, 100 mg/mL streptomycin, and 0.25 mg/mL amphotericin B) supplemented with 0.1% bovine serum albumin and 10 ng/mL transforming growth factor-b1.…”

Section: Cartilage Harvestmentioning

confidence: 99%

PRG4 exchange between the articular cartilage surface and synovial fluid

Nugent-Derfus

Chan

Schumacher

et al. 2007

Journal Orthopaedic Research

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ABSTRACT:The boundary lubrication function of articular cartilage is mediated in part by proteoglycan 4 (PRG4) molecules, found both in synovial fluid (SF) and bound to the articular cartilage surface. Currently the mechanism by which PRG4 binds to the articular surface is not well understood. The objectives of this study were to determine (1) the effect of bathing fluid contents on PRG4 concentration at the articular surface ([PRG4] cart ), and (2) whether native PRG4 can be removed from the surface and subsequently repleted with PRG4 from synovial fluid. In one experiment, cylindrical cartilage disks were stored in solutions of various PRG4 concentrations, either in phosphate-buffered saline (PBS) or SF as the carrier fluid. In a separate experiment, cartilage disks were stored in solutions expected to remove native PRG4 from the articular surface and allow subsequent repletion with PRG4 from SF. [PRG4] cart was independent of PRG4 concentration of the bathing fluid, and was similar for both carrier fluids. PRG4 was removed from cartilage by treatment with hyaluronidase, reduction/alkylation, and sodium dodecyl sulphate, and was repleted fully by subsequent bathing in SF. These results suggest that the articular surface is normally saturated with tightly bound PRG4, but this PRG4 can exchange with the PRG4 in SF under certain conditions. This finding suggests that all tissues surrounding the joint cavity that secrete PRG4 into the SF may help to maintain lubrication function at the articular surface. ß

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“…These observations suggest that the specific use of SZC and DZC may refine cellbased strategies for cartilage tissue regeneration. Indeed, several groups have attempted to layer SZC on top of DZC to engineer cartilage tissue with a morphology and function that is similar to normal cartilage (Kim et al, 2003;Klein et al, 2006;Klein et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Differences in matrix accumulation and hypertrophy in superficial and deep zone chondrocytes are controlled by bone morphogenetic protein

et al. 2007

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Despite the knowledge that superficial zone chondrocytes (SZC, located within 100 μm of the articular surface) and deep zone chondrocytes (DZC, located near the calcified zone) have distinct phenotypes, previous studies on bone morphogenetic proteins (BMPs) have not differentiated its effects on SZC versus DZC. Using a pellet culture model we have compared phenotype, morphology and matrix accumulation in SZC and DZC with or without adenovirus-mediated overexpression of BMP-2 or -7 or the BMP antagonist Noggin. Greater accumulation of proteoglycan (PG)-rich matrix in the untreated DZC was associated with a hypertrophic phenotype with large cell diameters and high gene expression levels of runt-related transcription factor-2 (Runx2) as well as higher endogenous BMP activity. Noggin overexpression decreased matrix accumulation and cell diameters in SZC and DZC, confirming a role for endogenous BMP in both processes. In DZC, overexpression of either BMP2 or -7 increased cell diameter without increasing PG-rich matrix accumulation. In contrast, in SZC, BMP overexpression increased matrix accumulation and type II collagen gene expression without increasing cell diameter. These data indicate that differences in endogenous BMP activity level and responsiveness to BMPs define, in part, the differences between the SZC and DZC phenotype. They also suggest that SZC may be a more appropriate target for BMP therapy than DZC.

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Tissue engineering of stratified articular cartilage from chondrocyte subpopulations

Abstract: Manipulation of subpopulations of chondrocytes can be useful in engineering cartilage tissue with a biomimetic approach, and in fabricating constructs that exhibit stratified features of normal articular cartilage.

Cited by 199 publications

References 40 publications

Shaped, Stratified, Scaffold-free Grafts for Articular Cartilage Defects

Shaped, Stratified, Scaffold-free Grafts for Articular Cartilage Defects

PRG4 exchange between the articular cartilage surface and synovial fluid

Differences in matrix accumulation and hypertrophy in superficial and deep zone chondrocytes are controlled by bone morphogenetic protein

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