# US 10,369,252 B2 · Electrospun three-dimensional nanofibrous scaffolds with interconnected and hierarchically structured pores

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- Number: US 10,369,252 B2
- Document ID: US10369252B2
- Status: Granted
- Kind: B2
- Application number: 15/539,517
- Filed: 2015-12-23
- Published: 2018-01-18
- Granted: 2019-08-06
- Earliest claimed: 2014-12-23
- Assignees: South Dakota Board of Regents
- Applicants: South Dakota Board of Regents
- Inventors: Hao Fong; Tao Xu; Yong Zhao; Todd J. Menkhaus
- Web page: https://patentgrep.com/patent/US10369252B2

## CPC

- A61L 27/18: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
- A61L 27/3834: {Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells}
- A61L 27/50: Materials characterised by their function or physical properties {, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials}
- A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)}
- A61L 27/56: Porous materials, {e.g. foams or sponges}
- D01D 5/003: {the material being a polymer solution or dispersion (D01D5/0053 takes precedence)}
- D01D 5/0092: {characterised by the electrical field, e.g. combined with a magnetic fields, using biased or alternating fields}
- D04H 1/4242: Carbon fibres
- D04H 1/728: by electro-spinning {(electro-spinning methods and apparatus D01D5/0007)}
- A61F 2/0077: {Special surfaces of prostheses, e.g. for improving ingrowth (A61F2/30767 takes precedence)}
- A61F 2/02: Prostheses implantable into the body
- A61F 2002/0086: {for preferentially controlling or promoting the growth of specific types of cells or tissues}
- A61F 2210/0004: bioabsorbable
- A61F 2240/001: Designing or manufacturing processes
- A61L 2300/64: Animal cells
- A61L 2400/12: Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
- A61L 2430/02: for reconstruction of bones; weight-bearing implants
- D01D 5/0007: {Electro-spinning (non-woven fabrics produced by electro-spinning D04H1/728)}
- D10B 2509/00: Medical; Hygiene
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- D01D: MECHANICAL METHODS OR APPARATUS IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS
- D04H: MAKING TEXTILE FABRICS, e.g. FROM FIBRES OR FILAMENTARY MATERIAL (weaving D03; knitting D04B; braiding D04C; net-making D04G; sewing D05B; tufting D05C; finishing non-woven fabrics D06); FABRICS MADE BY SUCH PROCESSES OR APPARATUS, e.g. FELTS, NON-WOVEN FABRICS; COTTON-WOOL; WADDING {; NON-WOVEN FABRICS FROM STAPLE FIBRES, FILAMENTS OR YARNS, BONDED WITH AT LEAST ONE WEB-LIKE MATERIAL DURING THEIR CONSOLIDATION}(non-woven fabrics having an intermediate or external layer of a different kind, e.g. of woven fabric, B32B)
- A61F: FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS (dental prosthetics A61C)
- D10B: INDEXING SCHEME ASSOCIATED WITH SUBLASSES OF SECTION D, RELATING TO TEXTILES

## Abstract

The invention relates to electrospun three-dimensional (3D) nanofibrous scaffolds (with controllable porosities as high as about 96%) and methods of preparing the same. The electrospun 3D scaffolds possess interconnected and hierarchically structured pores with sizes ranging from tens of nanometers to hundreds of micrometers. In embodiments, the 3D scaffolds can be biocompatible and/or biodegradable. In some embodiments, the 3D scaffolds can be conductive. In some embodiments, the 3D scaffolds can contain bioactive species.

## Claims

### Claim 1

A method for preparing a three-dimensional nanofibrous scaffold comprising:
forming a three-dimensional nanofibrous agglomerate by thermally induced nanofiber self-agglomeration; and
freeze-drying the three-dimensional agglomerate to obtain a three-dimensional nanofibrous scaffold.

### Claim 2 (depends on 1)

The method of claim 1, wherein said thermally induced nanofiber self-agglomeration is performed by steps comprising:
obtaining a nanofibrous mat;
grinding the nanofibrous mat to provide nanofibers and/or pieces of nanofibrous mat;
filtering the nanofibers and/or pieces of nanofibrous mat through a sieve having a pore size of about 0.5 mm to about 2 mm;
dispersing the filtered nanofibers and/or pieces of nanofibrous mat into a liquid system;
heating the liquid system at a temperature below the melting point of polymer to allow for nanofiber self-agglomeration to form a three-dimensional agglomerate;
cooling the liquid system to stop the self-agglomeration.

### Claim 3 (depends on 2)

The method of claim 2, wherein the nanofibrous mat is obtained by electrospinning a polymer to form a nanofibrous mat.

### Claim 4 (depends on 3)

The method of claim 3, wherein the polymer is biocompatible and/or biodegradable.

### Claim 5 (depends on 3)

The method of claim 3, wherein the polymer is selected from the group consisting of polycaprolactone, polylactic acid, polyglycolic acid, poly(lactic-co-glycolic acid), poly(lactic acid-co-caprolactone), polyhydroxyalkanoate, poly(3-hydroxybutyrate-co-3-hydroxyvalerate, poly(ester urethane), collagen, gelatin, regenerated silk, chitin, chitosan, cellulose, and their blends and/or composites.

### Claim 6 (depends on 3)

The method of claim 3, further comprising the addition of a viscosity modifier after the filtering step and before the heating step.

### Claim 7 (depends on 1)

The method of claim 1, wherein the three-dimensional scaffold is electrically conductive and further comprises conductive nanofibers comprising electrospun carbon nanofibers, vapor-grown carbon/graphite nanofibers, and/or non-conductive nanofibers surface-coated with a conductive layer.

### Claim 8 (depends on 6)

The method of claim 6, wherein the liquid system has a viscosity between about 5 cps and about 50 cps.

### Claim 9 (depends on 1)

The method of claim 1, wherein a substrate is added to the liquid system for controlling the shape of agglomerate prior to heating, and wherein the nanofibers and/or pieces of nanofibrous mat agglomerate on the surface of the substrate.

### Claim 10 (depends on 1)

The method of claim 1, further comprising sterilizing the three-dimensional nanofibrous scaffold and/or rinsing the three-dimensional nanofibrous scaffold with a cell culturing medium.

### Claim 11 (depends on 4)

The method of claim 4, wherein the three-dimensional nanofibrous scaffold comprises one or more bioactive species.