EP-4735018-A2 - CENTRIFUGALLY-MOLDED ARTICLES AND METHODS

Abstract

Centrifugal controlled biosolidification molding is disclosed. The methods involve use of aqueous solutions and centrifugal force in a unique processing method that produces highly uniform and useful articles from biopolymers that previously were formed by methods with significant shortcomings. In some cases, the technique uses a single biopolymer, which can produce highly uniform articles. In other cases, the technique uses different polymers, which can provide tailorable and tunable properties, such as desirable dissolution properties. Articles made by these methods overcome significant disadvantages from current techniques and exhibit a lack of external and internal layering and uniform bulk material.

Inventors

• KAPLAN, DAVID, L.
• FITZPATRICK, Vincent, P.
• LEUNG, Glenn

Assignees

• Trustees Of Tufts College

Dates

Publication Date

20260506

Application Date

20240701

Claims (20)

1. 1. A controlled centrifugal solidification biopolymer article, wherein the article is not a film, wherein at least a portion of the article comprises at least one characteristic centrifugal property selected from the group consisting of: i) a uniform density across the at least a portion of the article; ii) the at least a portion of the article is optically nontransparent; iii) the at least a portion of the article is free of exterior layering; iv) the at least a portion of the article is free of interior layering; v) the at least a portion of the article is interior- void-free; vi) the at least a portion of the article is free of cylindrical extrusion gaps; and vii) the at least a portion of the article is free of layering.
2. 2. A method of centrifugal controlled biosolidification molding, the method comprising the following sequential steps: A) introducing a first aqueous biopolymer solution into a mold and optionally settling the first aqueous biopolymer solution into the mold; B) introducing a first aqueous curing solution into the mold atop the first aqueous biopolymer solution and optionally settling the first aqueous curing solution into the mold, wherein the mold has a first orientation relative to gravity during step B); and C) subjecting the mold and contents of the mold to a first centrifugation and stopping after a first centrifugation length of time, thereby producing a first biosolidifying body, wherein the mold is within 45° of the first orientation relative to the first centrifugation during step C); wherein waiting a first final biosolidification length of time following step C) produces a first biopolymer article from the first biosolidifying body.
3. 3. The method of claim 2, wherein step A) includes settling the first aqueous biopolymer solution into the mold.
4. 4. The method of claim 3, wherein settling comprises subjecting the mold and the contents of the mold to a settling centrifugation and stopping after a settling centrifugation length of time, thereby conforming the first biopolymer solution to geometry of the mold, wherein the mold is within 45° of the first orientation relative to the first centrifugation during step B) during the settling centrifugation.
5. 5. The method of claim 3, wherein settling comprises tapping the mold and the contents of the mold on a surface, thereby conforming the first biopolymer solution to geometry of the mold, wherein the mold is within 45° of the first orientation relative to the first centrifugation during step B) during the tapping.
6. 6. The method of claim 2, the method further comprising waiting the first final biosolidification length of time following step C), thereby producing the first biopolymer article.
7. 7. The method of claim 2, wherein the first aqueous biopolymer solution is an aqueous silk solution, an aqueous alginate solution, an aqueous fibrinogen solution, an aqueous chitosan solution, an aqueous collagen solution, or a combination thereof.
8. 8. The method of claim 2, the method further comprising the following sequential steps: D) introducing a second aqueous biopolymer solution into the mold atop the first biosolidifying body and optionally settling the second aqueous biopolymer solution into the mold; E) introducing a second aqueous curing solution into the mold atop the second aqueous biopolymer solution and optionally settling the second aqueous curing solution into the mold, wherein the mold has a second orientation relative to gravity during step E); and F) subjecting the mold and contents of the mold to a second centrifugation and stopping after a second centrifugation length of time, thereby producing a second biosolidifying body inclusive of the first biosolidifying body, wherein the mold is within 45° of the second orientation relative to the second centrifugation in step F), wherein waiting a second final biosolidification length of time following step F) produces a second biopolymer article from the second biosolidifying body.
9. 9. The method of claim 8, the method further comprising waiting the second final biosolidication length of time following step F), thereby producing the second biopolymer article.
10. 10. The method of claim 8, wherein the second orientation is the same as the first orientation.
11. 11. The method of claim 8, wherein the second orientation is different than the first orientation.
12. 12. The method of claim 8, the method further comprising the following steps: G) introducing a third aqueous biopolymer solution into the mold atop the second biosolidifying body and optionally settling the third aqueous biopolymer solution into the mold; H) introducing a third aqueous curing solution into the mold atop the third aqueous biopolymer solution and optionally settling the third aqueous curing solution into the mold, wherein the mold has a third orientation relative to gravity during step H); and I) subjecting the mold and contents of the mold to a third centrifugation and stopping after a third centrifugation length of time, thereby producing a third biosolidifying body inclusive of the first and second biosolidifying bodies, wherein the mold is within 45° of the third orientation relative to the third centrifugation during step I), wherein waiting a third final biosolidifcation length of time following step I) produces a third biopolymer article from the third biosolidifying body.
13. 13. The method of claim 12, the method further comprising waiting the third final solidification length of time following step I), thereby producing the third biopolymer article.
14. 14. The method of claim 12, the method further comprising the following sequential steps: J) introducing a fourth aqueous biopolymer solution into the mold atop the third biosolidifying body and optionally settling the fourth aqueous biopolymer solution into the mold; K) introducing a fourth aqueous curing solution into the mold atop the fourth aqueous biopolymer solution and optionally settling the fourth aqueous curing solution into the mold, wherein the mold has a fourth orientation relative to gravity during step J); and L) subjecting the mold and contents of the mold to a fourth centrifugation and stopping after a fourth centrifugation length of time, thereby producing a fourth biosolidifying body inclusive of the first, second, and third biosolidifying bodies, wherein the mold is within 45° of the fourth orientation relative to the fourth centrifugation during step L), wherein waiting a fourth final biosolidifcation length of time following step L) produces a fourth biopolymer article from the fourth biosolidifying body.
15. 15. The method of claim 14, the method further comprising waiting the third final solidification length of time following step L), thereby producing the third biopolymer article.
16. 16. The method of any one of claims 2 to the immediately preceding claim, the method further comprising the following sequential steps: X) introducing an additional aqueous biopolymer solution atop existing portions of a biosolidifying body and optionally settling the additional aqueous biopolymer solution into the mold, the existing portions of the biosolidifying body inclusive of the first biosolidifying body and optionally inclusive of the second, third, and fourth biosolidifying bodies; Y) introducing an additional aqueous curing solution into the mold atop the additional aqueous biopolymer solution and optionally settling the additional aqueous curing solution into the mold; and Z) subjecting the mold and the contents of the mold to an additional centrifugation and stopping after an additional centrifugal length of time, thereby producing an additional biosolidifying body inclusive of the existing portions of the biosolidifying body, wherein waiting an additional final biosolidification length of time following step Z) producing an additional biopolymer article from the additional biosolidifying body.
17. 17. The method of claim 16, the method further comprising waiting the additional final solidification length of time following step Z), thereby producing the additional biopolymer article.
18. 18. A method of making a biopolymer article, the method comprising at least two iterative cycles of the following steps: X) introducing an iterative aqueous biopolymer solution into a mold and optionally settling the iterative aqueous biopolymer solution into the mold; Y) introducing an iterative aqueous curing solution into the mold atop the iterative aqueous biopolymer solution and optionally settling the iterative aqueous curing solution into the mold; and Z) subjecting the mold and the contents of the mold to an iterative centrifugation and stopping after an iterative centrifugal length of time, thereby iteratively adding to existing portions of the solidifying body, the iteratively introducing of step X), introducing of step Y), and subjecting of step Z) continuing until a final biosolidifying body is formed, wherein waiting a final biosolidification length of time following formation of the final biosolidification body produces the biopolymer article.
19. 19. The method of claim 18, the method further comprising waiting the final biosolidification length of time following step Z), thereby producing the biopolymer article.
20. 20. A method comprising: centrifuging a first early-stage-of-solidification aqueous biopolymer solution within a mold until a first later stage of solidification, thereby forming a first biosolidifying body.

Description

CENTRIFUGALLY-MOLDED ARTICLES AND METHODS CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application relates to, incorporates by reference for all purposes, and claims priority to United States Provisional Patent Application 63/511,572, filed June 30, 2023. GOVERNMENT FUNDING STATEMENT [0002] This invention was made with government support under P41EB027062 awarded by the National Institutes of Health. The government has certain rights in the invention. SEQUENCE LISTING [0003] A Sequence Listing accompanies this application and is submitted as an XML file of the sequence listing named “T002694 W0-2095.0612.xml” which is 32 kbytes in size and was created on June 23, 2024. The sequence listing is electronically submitted with the application and is incorporated herein by reference in its entirety. BACKGROUND [0004] Conventional silk processing techniques are capable of producing solid articles, but the current suite of techniques has shortcomings which results in articles having one or more undesirable properties. [0005] More broadly, biopolymer and polymer processing techniques presently lack a method of making a biopolymer article with material robustness that approaches more conventional polymers. [0006] Typical methods are limited by the diffusion of a polymerizing agent into the article. When an article reaches a certain size, the diffusion causes non-uniform crystallization. [0007] One existing technique of making silk articles is thermal molding and/or compression molding of silk powders. This has a variety of shortcomings, including an inability to elastic, non-brittle mechanical features. [0008] Another existing technique is silk fibroin-tailored injection molding. Distinct from traditional “melt-and-inject” processes, silk fibroin’s aqueous injection molding process has traditionally produced materials that are insufficiently uniform and have a high degree of interior voids. [0009] Yet another existing technique is three-dimensional printing. 3D printing using silk and biopolymers produces articles that have layered character and contain significant internal voids. In most cases, biopolymers are 3D printed using extrusion of cylinders of biopolymer, so there are large gaps between the cylinders of material. [0010] A need exists for new methods and articles that overcome one or more of the aforementioned shortcomings. SUMMARY [0011] Disclosed herein is a novel approach to molding biopolymers enabling the generation of complex geometries with high resolution, and centimeter- scale objects, using biopolymer solutions. This method rests on alternating deposition of material into a mold, centrifuging for shape conformity, and polymerizing the solution in situ. This process is repeated multiple times until the mold is filled, at which point the construct can be unmolded and polymerization can be finished. [0012] In one aspect, the present disclosure provides a controlled centrifugal solidification biopolymer article. [0013] In another aspect, the present disclosure provides a method of centrifugal controlled biosolidification molding. The method includes: A) introducing a first aqueous biopolymer solution into a mold and optionally settling the first aqueous biopolymer solution into the mold; B) introducing a first aqueous curing solution into the mold atop the first aqueous biopolymer solution and optionally settling the first aqueous curing solution into the mold, wherein the mold has a first orientation relative to gravity during step B); and C) subjecting the mold and contents of the mold to a first centrifugation and stopping after a first centrifugation length of time, thereby producing a first biosolidifying body, wherein the mold is within 45° of the first orientation relative to the first centrifugation during step C). Waiting a first final biosolidification length of time following step C) produces a first biopolymer article from the first biosolidifying body. [0014] In yet another aspect, the present disclosure provides a method of making a biopolymer article. The method includes at least two iterative cycles of the following steps: X) introducing an iterative aqueous biopolymer solution into a mold and optionally settling the iterative aqueous biopolymer solution into the mold; Y) introducing an iterative aqueous curing solution into the mold atop the iterative aqueous biopolymer solution and optionally settling the iterative aqueous curing solution into the mold; and Z) subjecting the mold and the contents of the mold to an iterative centrifugation and stopping after an iterative centrifugal length of time, thereby iteratively adding to existing portions of the solidifying body, the iteratively introducing of step X), introducing of step Y), and subjecting of step Z) continuing until a final biosolidifying body is formed. Waiting a final biosolidification length of time following formation of the final biosolidification body produces the biopolymer article. [0015] In yet another aspect