Manufacturing process, such as three dimensional printing, including binding of water-soluble material followed by softening and flowing and forming films of organic-solvent-soluble material

Abstract

The invention includes biostructures which may be characterized as having substantially all of the organic-solvent-soluble material in the form of a network of irregularly shaped perforated films. The biostructure may further include particles of a substantially-insoluble material, which may be a member of the calcium phosphate family. The biostructure may be osteoconductive. The biostructure may further contain an Active Pharmaceutical Ingredient or other bioactive substance. The API may be a substance which stimulates the production of bone morphogenetic protein, such as Lovastatin or related substances, thereby making the biostructure effectively osteoinductive. One or more of the polymers may have a resorption rate in the human body such as to control the release of the API. Methods of manufacture are also disclosed.

Description

CROSS-REFERENCE TO RELATED APPLICATION [0001] This application claims the benefit of U.S. Provisional patent application No. 60 / 570,412, filed May 12, 2004, the disclosure of which is herein incorporated by reference in its entirety.BACKGROUND OF THE INVENTION [0002] 1. Field of the Invention [0003] The invention pertains to the construction of biostructures for implantation into the human body or for growth of tissue. [0004] 2. Description of the Related Art [0005] Three-dimensional printing (3DP), described in U.S. Pat. No. 5,204,055, has proven to be useful for creating structures for a variety of purposes including medical applications such as bone substitutes and tissue scaffolds. [0006] In the three-dimensional printing process, a layer of powder has been deposited such as by roller spreading, and then a binder liquid has been dispensed onto the powder layer by techniques related to ink-jet printing. Powder particles have been joined together by the action of the binder liquid...

AI Technical Summary

Benefits of technology

[0018] The invention also includes methods of manufacturing such a biostructure starting from a powder mixture which contains both organic-solvent-soluble material and water-soluble material, and optionally also a substantially-insoluble material. A preform corresponding to the eventual biostructure may be manufactured by three-dimensional printing, which may be done by dispensing water or an aqueous binder liquid onto the powder mixture. The resulting preform may contain a structure of water-soluble material, with that water-soluble structure also holding other particles such as particles of organic-solvent-soluble material and (if present) particles of substantially-insoluble material. Then the organic-solvent-soluble material can be caused to soften and flow as a result of exposure to organic solvent vapor, or exposure to heat, or exposure to a substance in a supercritical or near-critical state. In this way, the organic-solvent-soluble material softens and flows and forms films, which closely follow the surface morphology of the water-soluble structure. Upon removal of the condition which causes softening and flowing, a hardened structure of organic-solvent-soluble material may be formed. This structure may retain substantially-insoluble particles which had been partially held by the water-soluble structure and which are also held by the film of organic-solvent-soluble material. This step may further be followed by dissolving out the water-soluble structure.

Problems solved by technology

Organic solvents such as chloroform have been more difficult to dispense from printheads than water or aqueous solutions, because of the combination of low viscosity and low surface tension which is characteristic of many organic solvents.

Chloroform in particular, even when it has been successfully dispensed from a printhead, has exhibited further difficulties which relate to how sharp a feature can be created during three-dimensional printing.

First of all, chloroform's unusually small surface tension and viscosity have given it an unusually large tendency to spread by capillary action in a powder bed.

Additionally, there has been a difficulty associated with the time scale at which chloroform evaporates.

Such a high saturation parameter has accelerated bleeding (migration) of binder liquid in the powder bed, which in turn has degraded dimensional resolution of printed features and has made it more difficult to remove unbound powder.

For example, bleeding has resulted in powder particles being attached to the printed region which are not really desired to be attached to the printed region.

Other difficulties associated with the use of chloroform and similar solvents during three dimensional printing have been the aggressive nature of both the liquid and the vapor of such solvents against components of the machine, and the toxicity of chloroform.

Another issue in 3DP has been that 3DP has tended to require adjustment of printing parameters to values which are unique to a particular combination of a powder mixture and a binder liquid being used.

If there is interest in many powders or solvents / binders and combinations thereof, then significant effort can be required to determine specific printing parameters.

Those structures were made by dispensing liquid chloroform from a printhead, which resulted in problems of bleeding of dispensed liquid in the powder bed, and so those articles did not have as sharp a dimensional resolution as might be desired.

However, this uses liquid chloroform, and is limited to the types of geometries which can be produced by molding and similar conventional manufacturing, and does not contain Active Pharmaceutical Ingredient and does not contain any member of the calcium phosphate family, which would be useful for bone growth.

However, this has not extended to three-dimensional printing.

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