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

Abstract

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.

Multi-pelvis characterisation of articular cartilage geometry

“…In addition to aiding implant design it has been suggested that characterising the acetabulum cartilage morphology could aid cartilage regeneration techniques (42). Current methods are limited by availability of donor tissue sources, donor site morbidity and prolonged rehabilitation times.…”

“…Current methods are limited by availability of donor tissue sources, donor site morbidity and prolonged rehabilitation times. Therefore second-generation tissue-engineered cartilaginous constructs which match the complex surface geometries of larger articular cartilage defects have been suggested to improve healing (42). Recently the hip has been suggested as a potential site for biologic resurfacing using shaped cartilaginous constructs in which a concave impression would be used to reconstruct the degenerated acetabulum (43).…”

Compaction Enhances Extracellular Matrix Content and Mechanical Properties of Tissue-Engineered Cartilaginous Constructs

“…There have been recent efforts to shape cartilaginous constructs using molding techniques. [40][41][42] Using molds with anatomical contours, the compaction method has the potential to mechanically impose a shape to the constructs or further maintain and improve the shaping fidelity of already-shaped constructs, which may facilitate fabrication of grafts for large cartilage defects with complex surface contours.…”

The Proteoglycan Metabolism of Articular Cartilage in Joint-Scale Culture

“…This allowed efficient usage of the available animal tissue. Groups included [1] fresh controls (n ¼ 18) or joints incubated for [2] 12 days (n ¼ 6) or [3] 28 days (n ¼ 5) at 378C without CX, for [4] 28 days (n ¼ 4) at 48C without CX, for 7 days at 48C and then 7 days at 378C (4=37) [5] without CX (n ¼ 3) or [6] with CX (n ¼ 3), or for [7] 14 days at 378C with CX (n ¼ 3) (Fig. 1A).…”

“…1,2 The shortage of available donor tissue 3 has stimulated tissue engineering efforts to generate large, appropriately shaped, joint-scale osteochondral fragments. [4][5][6][7][8] Allografts are currently stored at the joint scale, and the properties of cartilage in such stored allografts provide the standard for large tissue-engineered constructs.…”