Engineering mechanically functional human cartilage and method of making same
Inventors
Bhumiratana, Sarindr • Vunjak-Novakovic, Gordana
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Abstract
Medical devices having engineered mechanically functional cartilage from adult human mesenchymal stem cells and method for making same.
Core Innovation
The invention describes tissue-engineered mechanically functional human cartilage generated from adult human mesenchymal stem cells using transforming growth factor-b2-induced formation of condensed mesenchymal bodies. Condensed mesenchymal bodies are formed and then fused before mesenchymal condensation boundary setting, to support tissue-engineered cartilage. The approach is used to produce engineered cartilage and osteochondral constructs.
Engineered constructs are grown over decellularized porous bone matrices, including press-molding into anatomically shaped condyles, to obtain physiologic mechanics and tribology. The engineered cartilage includes a lubricin-rich superficial layer, collagen II in the bulk, and collagen X and collagen I at the bone interface and calcified region.
The document further describes condensed mesenchymal body dense cellular layers and condensed mesenchymal body penetration into porous scaffold pores within the decellularized bone matrix. An in vitro defect model is used to demonstrate cartilage repair with strong integration strength of the engineered cartilage/osteochondral constructs.
Claims Coverage
The partial content includes two independent claims that cover an anatomical scaffold with condensed mesenchymal bodies attached to a porous substrate, and a method for generating an osteochondral construct by culturing human mesenchymal stem cells to form condensed mesenchymal bodies and attaching them to a porous substrate. Across these independent claims, the core inventive concepts are limited to the condensed mesenchymal body–porous substrate relationship and its use in osteochondral construct generation.
Anatomical scaffold with condensed mesenchymal bodies attached to a porous substrate
The anatomical scaffold includes a porous substrate and condensed mesenchymal bodies attached to the porous substrate.
Generating an osteochondral construct by culturing mesenchymal stem cells to form condensed mesenchymal bodies and attaching them to a porous substrate
The method generates an osteochondral construct by culturing human mesenchymal stem cells to form condensed mesenchymal bodies and attaching the condensed mesenchymal bodies on a porous substrate.
The independent claims focus on condensed mesenchymal bodies attached to, or formed on and attached with, a porous substrate, and on using this condensed mesenchymal body attachment concept to generate an osteochondral construct.
Stated Advantages
Physiologic mechanics, including Young's modulus greater than 800 kPa.
Physiologic tribology, including an equilibrium friction coefficient less than 0.3.
Physiological stratification, including a lubricin-rich superficial layer and collagen stratification across the bulk and bone interface/calcified region.
Strong cartilage-cartilage integration in an in vitro defect model.
Documented Applications
An in vitro defect model for cartilage repair using engineered cartilage/osteochondral constructs generated from fused condensed mesenchymal bodies on decellularized porous bone matrices.
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