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Graft scaffold for cartilage repair and process for making same

A technology of cartilage repair and planting, applied in the field of three-dimensional grafts, which can solve problems such as misalignment, loose height, and incidence of donor sites

Active Publication Date: 2017-08-01
ETH ZZURICH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This treatment has several disadvantages, including donor site morbidity, scarcity of donor tissue, surgical difficulty, and the fact that the graft is composed of multiple segments, each of which may become loose or misaligned in height

Method used

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  • Graft scaffold for cartilage repair and process for making same
  • Graft scaffold for cartilage repair and process for making same
  • Graft scaffold for cartilage repair and process for making same

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1a

[0146] Example 1a: Bioprinting of Patient-Specific Tissue Grafts

[0147] Perform clinical computed tomography imaging to obtain computed three-dimensional objects ( figure 1 ). The patient-specific outer ear model is then mirrored to the contralateral side and a new 3D model is generated. Along with the new model, an external support structure model was generated to support the ear structure, especially the overhang area, during the printing process. Support structures are designed to contact the ink at strategically important locations to initiate cross-linking and support overhanging features ( Figure 5 ). Coextrusion of the support material was shown to keep horizontal bioink lines from sagging and accurately maintain the printed shape after elution of the support. Furthermore, the inner support structure of denser polymers is prepared to allow better force distribution in the inner structure ( figure 2 , 3 ). All models were converted into machine code in an S...

Embodiment 1b

[0149] Example 1b: Fabrication of cartilage particles for 3D printing purposes

[0150] Harvest cartilage from fresh bovine joint or ear cartilage by removing the thin layer of cartilage into a Petri dish containing PBS and 1% penicillin-streptomycin. The harvested cartilage was transferred to a cryogenic mill (Retsch) and milled at an intensity of 30 Hz for three cycles. The ground cartilage is collected and lyophilized to obtain a dry powder that can be sieved into the desired particle size range. These particles can be further loaded with growth factors or other molecules to enhance proliferation and other cellular responses. After loading, the particles are lyophilized and stored frozen to maximize the availability of biomolecules over an extended shelf life.

Embodiment 1c

[0151] Example 1c: Print mix material material preparation and printing process

[0152]A printing hybrid material ("Bio-Ink") was prepared by combining gellan gum at a concentration of 3.5% with 3% alginate. Gellan gum was dialyzed against ultrapure water to minimize cationic carryover in the material. Dialyze in ultrapure water at 70-80°C for 3 days, changing the water once or twice a day. The gellan gum was further lyophilized to obtain a dry powder. Purified gellan gum was dissolved in deionized water containing dextrose to make it more compatible with cells, and the alginate solution was added to obtain the final concentration of the polymer. Combine the polymer blend with ECM particles and 6 x 10 6 Cells / ml were mixed to obtain the final printed mixed material. Compared with the positive control, the printing mixture significantly stimulated cell proliferation ( Figure 4 ). For bioink alone, bioink + ECM with or without the growth factor TGF-β3, cartilage extr...

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Abstract

The present invention relates to a method of providing a graft scaffold for cartilage repair, particularly in a human patient. The method of the invention comprising the steps of providing particles and / or fibres; providing an aqueous solution of a gelling polysaccharide; providing mammalian cells; mixing said particles and / or fibres, said aqueous solution of a gelling polysaccharide and said mammalian cells to obtain a printing mix; and depositing said printing mix in a three-dimensional form. The invention further relates to graft scaffolds and grafts obtained by the method of the invention.

Description

technical field [0001] The present invention relates to a three-dimensional implant, in particular for repairing craniofacial appearance and damaged joints, and a method of manufacturing patient-specific implants using computer-aided modeling and three-dimensional bioprinting with biocompatible inks . Background technique [0002] Reconstruction of the nose and outer ear in a patient-specific manner is one of the greatest challenges in plastic surgery because of the complex three-dimensional nature of the internal cartilage structure, as well as regional variations in mechanical properties and overlying skin. Auricle reconstruction is indicated for congenital malformations, microtia, melanoma-related tissue sacrifice and injury, including accidents and severe burns. About 90 percent of head and neck burns involve the ears. The most common standard treatment for total auricle reconstruction in the United States and the European Union is a two- to three-stage surgical techni...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61L27/54A61L27/50A61L27/20A61L27/36A61L27/38A61L27/46A61L27/48B33Y10/00B33Y70/00
CPCB33Y10/00A61L27/20A61L27/3612A61L27/3817A61L27/3852A61L27/46A61L27/48A61L27/50A61L27/54A61L2300/414A61L2430/06B33Y70/10C08L5/00B33Y30/00A61L27/52A61L27/26C08L5/04A61K9/00B33Y50/02B33Y80/00A61L27/3856G05B2219/35134G05B19/4099G05B2219/49007
Inventor M·凯斯蒂M·泽诺比-黄M·穆勒
Owner ETH ZZURICH