US4955893A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Prosthesis for promotion of nerve regeneration
Assignee: Massachusetts Institute of Technology
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Filing: 1989-03-23
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Granted: 1990-09-11
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Expires: 2009-03-23
Abstract
Abstract A method for producing a biodegradable polymer having a preferentially oriented pore structure and a method for using the polymer to regenerate damaged nerve tissue is disclosed. The preferentially oriented pores are produced by an axial freezing process and serve to promote proper vascularation and regeneration of the damaged nerve. Preferably, the biodegradable polymer comprises uncrosslinked collagen-glycosaminoglycan.
Inventors
- 👤 Ioannis V. Yannas
- 👤 Dennis P. Orgill
- 👤 II Howard M. Loree
- 👤 James F. Kirk
- 👤 Albert S. P. Chang
- 👤 Borivoje B. Mikic
- 👤 Christian Krarup
- 👤 Thorkild V. Norregaard
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-22 23:17
CPC Classifications
A; A61; A61L; A61L27/00; A61L27/14; A61L27/22; A61L27/24; A61B; A61B17/00; A61B17/11; A61B17/1128; A61B2017/00004; A61F; A61F2310/00; A61F2310/00005; A61F2310/00365; A61L2430/00; A61L2430/32; Y; Y10; Y10S; Y10S128/00; Y10S128/08; Y10S623/00; Y10S623/92
Claims Analysis
Total Claims: 41
Claim 1
Independent Claim
132 words
A prosthetic device for axonal regeneration of nerve tissue, said device comprising a porous, biodegradable template with preferentially oriented pores, made by a method comprising the steps of: a. introducing an aqueous suspension of collagen-glycosaminoglycan into a tubular mold; b. lowering the tube axially into a liquid cooling bath sufficient to freeze the suspension, the lowering being at a rate such that ice crystals oriented parallel to the axis are formed; c. sectioning the mold to provide at least one prosthesis; d. exposing the frozen material to a vacuum under conditions which cause the ice crystals to sublime, thereby forming a regeneration template with preferentally oriented pores having an average pore diameter sufficient for axonal regeneration; and e. providing a means for maintaining contact between the regeneration template and a nerve end.
Claim 2
Dependent Claim
132 words
A prosthetic device for axonal regeneration of nerve tissue, said device comprising a porous, biodegradable template with preferentially oriented pores, made by a method comprising the steps of: a. introducing an aqueous suspension of collagen-glycosaminoglycan into a tubular mold; b. lowering the tube axially into a liquid cooling bath sufficient to freeze the suspension, the lowering being at a rate such that ice crystals oriented parallel to the axis are formed; c. sectioning the mold to provide at least one prosthesis; d. exposing the frozen material to a vacuum under conditions which cause the ice crystals to sublime, thereby forming a regeneration template with preferentally oriented pores having an average pore diameter sufficient for axonal regeneration; and e. providing a means for maintaining contact between the regeneration template and a nerve end.
Claim 3
Dependent Claim
13 words
A prosthetic device as claimed in claim 1 wherein the collagen-glycosaminoglycan is crosslinked.
Claim 4
Dependent Claim
17 words
A prosthetic device as claimed in claim 1 wherein the mole comprises a medical grade, silicone tube.
Claim 5
Independent Claim
164 words
A method for axonal regeneration of nerve tissue, comprising the steps of: a. providing a porous, biodegradable regeneration template having preferentially oriented pores, said template made by the process comprising: (i) introducing an aqueous suspension of a biodegradable polymer into a tubular mold, said biodegradable polymer comprising the material of the template; (ii) lowering the mold axially into a liquid cooling bath sufficient to freeze the suspension, the lowering being at a rate such that ice crystals oriented parallel to the axis of the mold are formed; and (iii) exposing the frozen material to a vacuum under conditions which cause the ice crystals to sublime, thereby forming a preferentially oriented pore structure, b. contacting a severed end of nerve tissue at each peripheral end of the regeneration template, said template oriented in a manner such that the pores of the template are oriented axially with the nerve ends; and c. providing a means to maintain contact between the nerve ends and the regeneration template.
Claim 6
Independent Claim
164 words
A method for axonal regeneration of nerve tissue, comprising the steps of: a. providing a porous, biodegradable regeneration template having preferentially oriented pores, said template made by the process comprising: (i) introducing an aqueous suspension of a biodegradable polymer into a tubular mold, said biodegradable polymer comprising the material of the template; (ii) lowering the mold axially into a liquid cooling bath sufficient to freeze the suspension, the lowering being at a rate such that ice crystals oriented parallel to the axis of the mold are formed; and (iii) exposing the frozen material to a vacuum under conditions which cause the ice crystals to sublime, thereby forming a preferentially oriented pore structure, b. contacting a severed end of nerve tissue at each peripheral end of the regeneration template, said template oriented in a manner such that the pores of the template are oriented axially with the nerve ends; and c. providing a means to maintain contact between the nerve ends and the regeneration template.
Claim 7
Dependent Claim
14 words
A method as claimed in claim 4 wherein the biodegradable regeneration template comprises collagen-glycosaminoglycan.
Claim 8
Dependent Claim
12 words
A method as claimed in claim 5 wherein the collagen-glycosaminoglycan is crosslinked.
Claim 9
Dependent Claim
17 words
A prosthetic device of for axonal regeneration of nerve tissue made by the method of claim 1.
Claim 10
Dependent Claim
31 words
The prosthetic device of claim 7 wherein the biodegradable polymer is contained within a tubular mold, comprising nonbiodegradable material having an internal diameter large enough to insert damaged nerve fibers therein.
Claim 11
Dependent Claim
12 words
The prosthetic device of claim 7 wherein the biodegradable polymer comprises collagen-glycosaminoglycans.
Claim 12
Dependent Claim
11 words
The prosthetic device of claim 9 wherein the collagen-glycosaminoglycan is crosslinked.
Claim 13
Independent Claim
97 words
A method for producing a porous, biodegradable template for axonal regeneration of nerve tissue, comprising the steps of: a. introducing an aqueous suspension of a biodegradable polymer into a tubular mold for said template; b. lowering the tube axially into a liquid chilled below the freezing point of the suspension, the lowering being at a rate such that ice crystals oriented parallel to the axis are formed; and c. exposing the frozen suspensions to a vacuum under conditions which cause the ice crystals to sublime, thereby forming a porous biodegradable template having a preferentially oriented pore structure.
Claim 14
Independent Claim
97 words
A method for producing a porous, biodegradable template for axonal regeneration of nerve tissue, comprising the steps of: a. introducing an aqueous suspension of a biodegradable polymer into a tubular mold for said template; b. lowering the tube axially into a liquid chilled below the freezing point of the suspension, the lowering being at a rate such that ice crystals oriented parallel to the axis are formed; and c. exposing the frozen suspensions to a vacuum under conditions which cause the ice crystals to sublime, thereby forming a porous biodegradable template having a preferentially oriented pore structure.
Claim 15
Dependent Claim
82 words
In the process for producing biodegradable templates for axonal regeneration of nerve tissue which comprises providing an aqueous suspension of a biodegradable, polymeric material, freezing the suspension to produce preferentially oriented ice crystals, and causing the ice crystals to sublime thereby providing preferentially oriented pores, the improvement which comprises producing the preferentially oriented ice crystals by axially immersing a mold containing the aqueous suspension in a chilled liquid, said axial immersion proceeding in a direction substantially parallel to the preferred pore orientation.
Claim 16
Dependent Claim
82 words
In the process for producing biodegradable templates for axonal regeneration of nerve tissue which comprises providing an aqueous suspension of a biodegradable, polymeric material, freezing the suspension to produce preferentially oriented ice crystals, and causing the ice crystals to sublime thereby providing preferentially oriented pores, the improvement which comprises producing the preferentially oriented ice crystals by axially immersing a mold containing the aqueous suspension in a chilled liquid, said axial immersion proceeding in a direction substantially parallel to the preferred pore orientation.
Claim 17
Independent Claim
98 words
A method for producing a porous, biodegradable template for axonal regeneration of nerve tissue, comprising the steps of: a. introducing an aqueous suspension of a biodegradable polymer into a tubular mold for said template; b. introducing the mold into a liquid cooling bath under conditions suitable to freeze the suspension of biodegradable polymer axially along the tubular mold to provide preferentially oriented ice crystals within the frozen suspension; and c. exposing the frozen suspension to a vacuum under conditions with cause the ice crystals to sublime, thereby forming a porous biodegradable template having a preferentially oriented pore structure.
Claim 18
Independent Claim
98 words
A method for producing a porous, biodegradable template for axonal regeneration of nerve tissue, comprising the steps of: a. introducing an aqueous suspension of a biodegradable polymer into a tubular mold for said template; b. introducing the mold into a liquid cooling bath under conditions suitable to freeze the suspension of biodegradable polymer axially along the tubular mold to provide preferentially oriented ice crystals within the frozen suspension; and c. exposing the frozen suspension to a vacuum under conditions with cause the ice crystals to sublime, thereby forming a porous biodegradable template having a preferentially oriented pore structure.
Claim 19
Dependent Claim
12 words
A method as in claim 13 wherein the biodegradable polymer comprises collagen-glycosaminoglycans.
Claim 20
Dependent Claim
11 words
A method as in claim 14 wherein the collagen-glycosaminoglycan is crosslinked.
Claim 21
Dependent Claim
15 words
A method as in claim 13 wherein the mold comprises a medical grade, silicone tube.
Claim 22
Dependent Claim
21 words
A method as in claim 13 wherein the aqueous suspension is frozen by axially immersing the mold in a chilled liquid.
Claim 23
Dependent Claim
17 words
A method as in claim 17 wherein the chilled liquid comprises silicone oil cooled with liquid nitrogen.
Claim 24
Dependent Claim
16 words
A method as in claim 17 wherein the chilled liquid is maintained at a constant temperature.
Claim 25
Dependent Claim
40 words
A method as claimed in claim 13 wherein the aqueous suspension within the mold is lowered into the liquid cooling bath at a rate of from about 2.0×10 -5 to about 10 -4 m/s until said mold is completely immersed.
Claim 26
Dependent Claim
20 words
A method as claimed in claim 14 wherein the collagen-glycosaminoglycan in suspension is from about 0.12% to about 0.96% w/w.
Claim 27
Dependent Claim
29 words
A method as in claim 1 wherein the frozen suspension is exposed to a vacuum for a period of time sufficient to allow substantially all ice crystals to sublime.
Claim 28
Independent Claim
106 words
A method for producing a porous, biodegradable template, useful for axonal regeneration of nerve tissue, comprising the steps of: a. introducing an aqueous suspension of a biodegradable polymer into a tubular mold for said template; b. introducing the mold into a constant temperature liquid cooling bath at a controlled velocity and under conditions suitable to freeze the suspension of biodegradable polymer axially along the tubular mold to provide preferentially oriented ice crystals within the frozen suspension; and c. exposing the frozen suspension to a vacuum, under conditions which cause the ice crystals to sublime, thereby forming a porous biodegradable template having a preferentially oriented pore structure.
Claim 29
Independent Claim
106 words
A method for producing a porous, biodegradable template, useful for axonal regeneration of nerve tissue, comprising the steps of: a. introducing an aqueous suspension of a biodegradable polymer into a tubular mold for said template; b. introducing the mold into a constant temperature liquid cooling bath at a controlled velocity and under conditions suitable to freeze the suspension of biodegradable polymer axially along the tubular mold to provide preferentially oriented ice crystals within the frozen suspension; and c. exposing the frozen suspension to a vacuum, under conditions which cause the ice crystals to sublime, thereby forming a porous biodegradable template having a preferentially oriented pore structure.
Claim 30
Dependent Claim
12 words
A method as in claim 23 wherein the biodegradable polymer comprises collagen-glycosaminoglycans.
Claim 31
Dependent Claim
11 words
A method as in claim 24 wherein the collagen-glycosaminoglycan is crosslinked.
Claim 32
Dependent Claim
15 words
A method as in claim 23 wherein the mold comprises a medical grade, silicone tube.
Claim 33
Dependent Claim
21 words
A method as in claim 23 wherein the aqueous suspensions is frozen by axially immersing the mold in a chilled liquid.
Claim 34
Dependent Claim
17 words
A method as in claim 27 wherein the chilled liquid comprises silicone oil cooled with liquid nitrogen.
Claim 35
Dependent Claim
16 words
A method as in claim 27 wherein the chilled liquid is maintained at a constant temperature.
Claim 36
Dependent Claim
40 words
A method as claimed in claim 23 wherein the aqueous suspension within the mold is lowered into the liquid cooling bath at a rate of from about 2.0×10 -5 to about 10 -4 m/s until said mold is completely immersed.
Claim 37
Dependent Claim
20 words
A method as claimed in claim 24 wherein the collagen-glycosaminoglycan in suspension is from about 0.12% to about 0.96% w/w.
Claim 38
Dependent Claim
28 words
A method of claim 23 wherein the frozen suspension is exposed to a vacuum for a period of time sufficient to allow substantially all ice crystals to sublime.
Claim 39
Independent Claim
120 words
A method for producing a porous, biodegradable template for axonal regeneration of nerve tissue, comprising the steps of: a. introducing an aqueous suspension of collagen-glycosaminoglycan into a tubular mold; b. introducing the mold into a constant temperature cooling bath at a velocity of from about 2.0×10 -5 to about 10 -4 m/s until the mold is completely immersed, under conditions suitable to freeze the suspension of collagen-glycosaminoglycan axially along the tubular mold to provide preferentially oriented ice crystals within the frozen suspension; and c. exposing the frozen suspension to a vacuum for a period of time sufficient to allow substantially all of the ice crystals to sublime, thereby forming a porous biodegradable template having a preferentially axially oriented pore structure.
Claim 40
Independent Claim
120 words
A method for producing a porous, biodegradable template for axonal regeneration of nerve tissue, comprising the steps of: a. introducing an aqueous suspension of collagen-glycosaminoglycan into a tubular mold; b. introducing the mold into a constant temperature cooling bath at a velocity of from about 2.0×10 -5 to about 10 -4 m/s until the mold is completely immersed, under conditions suitable to freeze the suspension of collagen-glycosaminoglycan axially along the tubular mold to provide preferentially oriented ice crystals within the frozen suspension; and c. exposing the frozen suspension to a vacuum for a period of time sufficient to allow substantially all of the ice crystals to sublime, thereby forming a porous biodegradable template having a preferentially axially oriented pore structure.
Claim 41
Dependent Claim
20 words
A method as claimed in claim 33 wherein the collagen-glycosaminoglycan in suspension is from about 0.12% to about 0.96% w/w.
References Cited (Backward Citations)
US4522753A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1993-09-10 | 1994-03-12 | 1994-09-11 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1997-09-10 | 1998-03-12 | 1998-09-11 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2001-09-10 | 2002-03-12 | 2002-09-11 | $7700.00 | Window Closed / Lapsed |