Nanofiber-hydrogel composites for enhanced soft tissue replacement and regeneration

a technology of nanofiber and hydrogel, applied in the field of composite materials, can solve the problems of donor site defects, fibrosis and encapsulation, and difficult treatment of soft tissue defects resulting from trauma, oncologic resection, or congenital malformations by conventional means, and achieve the effect of improving the quality of soft tissue reconstruction and improving the properties

Pending Publication Date: 2021-12-30
THE JOHN HOPKINS UNIV SCHOOL OF MEDICINE
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Soft tissue defects resulting from trauma, oncologic resection, or congenital malformation are difficult to treat by conventional means.
Current therapies, including tissue rearrangements or tissue transfer, cause donor site defects.
Other therapies, such as prosthetic implants, lead to fibrosis and encapsulation.
Existing strategies to promote tissue ingrowth are also inadequate for the treatment of soft tissue defects.
Current acellular matrices result in flat, fibrotic sheets of tissue rather than the soft, three-dimensional tissue required for ideal reconstructions.
Finally, while fat grafting can restore soft tissue defects, its wider use is hampered by variable graft survival and limited volumes of restoration.
While several hydrogels have shown some benefits in soft tissue reconstruction, there is no current material that is able to address all of the mechanical challenges in succession.
Under these conditions, however, host tissue cells (e.g., adipocyte progenitors and endothelial progenitors) are not able to penetrate and grow into the scaffolds.
In case of degradable hydrogels, scarring and fibrous tissue formation are typical because ingrowth of host tissue occurs too slowly, or at least at a pace slower than the absorption of the fiber material.
These nanofibers, however, do not offer macroscopic structures, making them difficult to use as 3D scaffolds.
Many commercialized hydrogel fillers cause moderate to severe inflammation in the patient, while not retaining full original volume over time.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Nanofiber-hydrogel composites for enhanced soft tissue replacement and regeneration
  • Nanofiber-hydrogel composites for enhanced soft tissue replacement and regeneration
  • Nanofiber-hydrogel composites for enhanced soft tissue replacement and regeneration

Examples

Experimental program
Comparison scheme
Effect test

example 1

orming Composite with Reduced Inflammation Profiles

[0243]An in situ-forming composite was developed comprising 5 mg / mL of thiolated HA (HA-SH), 10 mg / mL of polycaprolactone (PCL) fibers and the concentration of PEGDA set to match the thiol concentration 1:1 with the combined acrylate and maleimide concentrations (5 mg / mL). The components were mixed together to react approximately 30 minutes before surgery in order to begin gelation, with the bulk of the gelation being completed in situ.

[0244]While gelation success was achieved in vitro and in animals (rodents and rabbits by subcutaneous (s.c.) injection), the chemistry preparation utilizing the thiolated-HA caused short-term moderate inflammation when injected in the subcutaneous rabbit model. In order to produce a composite formulation with reduced inflammation, the reactive groups between the HA and PEG were reversed, keeping an earlier formulation comprising a fiber-maleimide component.

[0245]As shown in FIG. 1A, the upward arrows...

example 2

ed Composite Beads with New Composition

[0252]To improve storage stability and make the gel simpler and more consistent for the end-user, a gel was formed comprising a pre-reacted, beaded formulation, wherein the formulation (7 mg / mL HA-Ac, 8 to 10 mg / mL of fibers with maleimide, and 6.9 m / mL of PEGSH) is fully reacted in bulk at 37° C. By pre-reacting the gel during manufacturing, the labile functional groups did not need to be protected, and the need for extensive mixing and curing by the end-user was removed.

[0253]The bulk gel is formed into 150 or 250 μm beads, then lyophilized in an isotonic solution of sucrose, trehalose, and sodium chloride (to protect the microstructure during the drying process and extend the product's shelf life). The gel beads are then reconstituted with water and within seconds are ready for injection, with the same storage modulus as prior to lyophilization. Optical microscopy images of the beaded composite are shown in FIG. 2. FIG. 2A shows the composit...

example 3

emical Characterization of Composite Beads

Determination of Size Distribution

[0255]Diameters of composite beads were measured along the longest axis of the particles under a confocal microscope image. The analysis were performed counting 51 particles. Histogram of the particles (FIG. 2G) gives the average bead size as 209.41±62.27 μm. FIG. 2H demonstrates confocal microscope images of beads of size ˜75 μm, ˜150 μm and ˜200 μm by measuring the longest axis within the particle.

[0256]Further characterized bead size distribution is performed using image analysis program that will use edge detection for more consistent measurements.

[0257]In some embodiments, different mesh size sieves used to process the bulk composite can yield to different histograms for the bead sizes.

[0258]In an alternative embodiment, SEM (Scanning Electron Microscopy) is used to image composite beads. Staining of the hydrogel or fibers may be required during the imaging process.

Assessing Injectability Based on Size ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
concentrationaaaaaaaaaa
mean lengthaaaaaaaaaa
mean sizeaaaaaaaaaa
Login to view more

Abstract

A composite material can include a gel and at least one nanostructure disposed within the gel. A method for healing a soft tissue defect can include applying a composite material to a soft tissue defect, wherein the composite material includes a gel and a nanostructure disposed within the gel. A method for manufacturing a composite material for use in healing soft tissue defects can include providing a gel and disposing nanofibers within the gel.

Description

[0001]This application claims the benefit of U.S. Provisional Application 62 / 669,307 filed May 9, 2018, which is incorporated by reference herein in its entirety.GOVERNMENT SUPPORT[0002]This invention was made with government support under grant no. 1R21NS085714 awarded by the U.S. National Institutes of Health and grant no. DMR1410240 awarded by the National Science Foundation. The government has certain rights in the invention.BACKGROUNDField[0003]The present disclosure relates to composite materials and methods that restore lost soft tissue volume while promoting soft tissue regeneration. The present invention also relates to composite materials and methods for cosmetic, and reconstructive purposes.Description of Related Art[0004]Soft tissue defects resulting from trauma, oncologic resection, or congenital malformation are difficult to treat by conventional means. Current therapies, including tissue rearrangements or tissue transfer, cause donor site defects. Other therapies, suc...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(United States)
IPC IPC(8): A61L27/48A61L27/36A61L27/56A61L27/54
CPCA61L27/48A61L27/3633A61L27/56A61L2300/62A61L2430/34A61L2400/06A61L2300/236A61L27/54C08L5/08A61L27/52A61L27/20A61L2400/12
Inventor MARTIN, RUSSELLREDDY, SASHANKCOLBERT, KEVINMAO, HAI-QUAN
Owner THE JOHN HOPKINS UNIV SCHOOL OF MEDICINE
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap