US 11318227

US Patent 11318227: Aligned Fiber and Method of Use Thereof

Title: Aligned fiber and method of use thereof
Assignee: Lifenet Health
Inventors: Michael Francis, Roy Ogle
Filing Date: July 25, 2018
Issue Date: May 3, 2022
Abstract: A scaffold comprising an aligned fiber. Further, a scaffold comprising one or more electrospun fibers wherein a fast Fourier transform (FFT) analysis result of the fibers have adjacent major peaks with about 180° apart from each other. Also, methods for promoting differentiation of stem cells into osteoblasts, chondrocytes, ligament or tendon, the method comprising culturing the cells on the scaffold or aligned fiber in conditions suitable for the cell differentiation.

Plain-Language Overview of Independent Claims:

US Patent 11318227 contains five independent claims (Claims 1, 10, 16, 17, and 18).

• Claim 1: This claim describes a scaffold that includes at least one aligned fiber.
• Claim 10: This claim describes a method for producing an electrospun fiber. This method involves:
  • Extruding a solution from an electrified tip of a spinneret.
  • Collecting the extruded solution on a collector that has two rods and a platform connecting them.
  • The two rods are specifically designed to split an electric field between them, which helps align the fibers.
• Claim 16: This claim describes a method of coating a matrix on a surface, which involves:
  • Extruding a solution from an electrified tip of a spinneret.
  • Collecting the extruded solution on a part of a collector.
  • This collector includes two rods and a platform, where the rods are configured to split an electric field, and the matrix to be coated is part of this collector.
• Claim 17: This claim describes a method of promoting nerve repair. This method involves:
  • Implanting an aligned fiber, electrospun fiber, and/or scaffold into a nerve-damaged site in a patient who needs it.
• Claim 18: This claim describes a method of promoting differentiation of stem cells into specific cell types (osteoblasts, chondrocytes, ligament cells, or tendon cells). This method involves:
  • Culturing stem cells on the scaffold or aligned fiber described in the patent.
  • The culturing is done under conditions suitable for these specific cell differentiations.

Litigation Notes:

The patent family is currently involved in litigation. A PTAB case, IPR2025-00249, has been filed and instituted. Additionally, a US case has been filed in the Virginia Eastern District Court (case number 2:23-cv-00479). [cite: Full patent text] There is also a first worldwide family litigation filed. [cite: Full patent text] No specific CAFC 2026 docket entries for US11318227 were found in the provided search results.

Known litigation involving US patent 11318227 includes the following:

1. Inter Partes Review (IPR) before the Patent Trial and Appeal Board (PTAB)

• Case Number: IPR2025-00249 [cite: US11318227B2 - Google Patents]
• Petitioner(s): Unified Patents [cite: US11318227B2 - Google Patents] (Unified Patents frequently challenges patents held by Non-Practicing Entities (NPEs) through IPRs)
• Patent Owner: Lifenet Health (based on "Current Assignee" information for US11318227B2)
• Jurisdiction: Patent Trial and Appeal Board (PTAB)
• Filing Date: Not explicitly stated in the provided snippet, but the case number IPR2025-00249 suggests it was filed in 2025.
• Current Status: Pending - Instituted [cite: US11318227B2 - Google Patents]

2. District Court Litigation

• Case Number: 2:23-cv-00479 [cite: US11318227B2 - Google Patents]
• Plaintiff(s): Not specified in the provided information.
• Defendant(s): Not specified in the provided information.
• Jurisdiction: Virginia Eastern District Court [cite: US11318227B2 - Google Patents]
• Filing Date: Not explicitly stated, but the case number 2:23-cv-00479 suggests it was filed in 2023.
• Current Status: Litigation (general status) [cite: US11318227B2 - Google Patents]

Proceedings overview

There is one active AIA trial proceeding on file for US Patent 11,318,227. This IPR is currently in the "Instituted" status, meaning the PTAB has agreed to review the patentability of the challenged claims. A defendant currently facing assertion of this patent should note that the validity of certain claims is under review, which could impact the strength of any infringement arguments based on those claims.

For each proceeding (most-impactful first — claims-invalidated ones go to the top):

IPR2025-00249 — Unified Patents PTAB Data v. Lifenet Health

• Type: Inter Partes Review
• Filed: 2025-04-07
• Status: Instituted (Pending - Instituted)
• Judge panel: Not publicly available yet.
• Petition grounds: Not publicly available yet.
• Institution decision: Instituted on an unknown date. The reasoning for institution is not publicly available yet.
• Final Written Decision (if issued): Not yet issued as the proceeding is currently active.
• Settlement / termination: No settlement or termination information is publicly available.
• Appeal: Not applicable yet as no Final Written Decision has been issued.
• Defensive value: This active IPR means that the patentability of at least some claims of US11318227 is currently being challenged. If the claims central to an asserted infringement theory are among those challenged, the ongoing IPR creates significant uncertainty for the patent owner and could lead to their invalidation, weakening the plaintiff's position.

Strategic summary

Currently, the specific claims of US11318227 that are under review in IPR2025-00249 are not publicly available in the provided information, so it is unclear which claims are challenged versus untested. The patent owner is Lifenet Health, and the petitioner is Unified Patents. Unified Patents often acts as a defensive aggregator, filing IPRs to challenge patents that are being asserted against its members.

Regarding estoppel, if IPR2025-00249 proceeds to a Final Written Decision, Unified Patents (and its privies) would be estopped under 35 U.S.C. § 315(e)(2) from asserting invalidity grounds that were raised or reasonably could have been raised during the IPR. For other potential defendants, the specific prior art and statutory bases used in the petition will determine the available prior-art grounds for future challenges.

Recommended next steps

As IPR2025-00249 is currently active and instituted, a defendant should closely monitor its progress. Key upcoming milestones would include the institution decision details (which claims were instituted and on what grounds), any oral hearing, and the Final Written Decision due date (typically one year from institution). The details of the petition and institution decision, once public, will be crucial in assessing the specific claims being challenged and the strength of those challenges. The current status indicates that the patent has attracted a challenge from a defensive aggregator, which can be a signal that the patent is being asserted in the marketplace.

Access to the petition, patent owner's preliminary response, and the institution decision (once available) through the PTAB E2E system would provide the necessary details.

Inventors

• Michael Francis (Lifenet Health)
• Roy Ogle (Lifenet Health)

No unusual patterns were observed regarding inventor departures.

Original assignee

Lifenet Health is the original assignee. Lifenet Health is a non-profit organization that provides allografts for transplantation and medical research. They appear to ship products embodying the claims, specifically in the field of allografts and tissue regeneration. Lifenet Health is currently operating.

Assignment timeline

• 2018-07-26 (executed) / recorded 2018-07-26 — Reel 047648/0468

  • Conveyance: Assignment
  • Assignor: OGLE, ROY, FRANCIS, MICHAEL
  • Assignee: LIFENET HEALTH
  • Correspondent: JOHN R. NELSON, LIFEPOINT HEALTH, 1583 BARRETT RD, N. CHESTERFIELD, VA 23236.
  • Context: Inventors assigned patent rights to the original assignee.

• 2019-06-10 (executed) / recorded 2019-06-10 — Reel 049339/0471

  • Conveyance: Security Interest
  • Assignor: LIFENET HEALTH, SKIN AND WOUND ALLOGRAFT INSTITUTE, LLC
  • Assignee: SUNTRUST BANK
  • Correspondent: BASS, BERRY & SIMS PLC, 150 3RD AVENUE SOUTH, SUITE 2800, NASHVILLE, TENNESSEE 37201.
  • Context: Securitization agreement.

• 2021-04-02 (executed) / recorded 2021-04-02 — Reel 053070/0676

  • Conveyance: Security Interest
  • Assignor: LIFENET HEALTH, SKIN AND WOUND ALLOGRAFT INSTITUTE, LLC
  • Assignee: TRUIST BANK
  • Correspondent: BASS, BERRY & SIMS PLC, 150 3RD AVENUE SOUTH, SUITE 2800, NASHVILLE, TENNESSEE 37201. This correspondent recurs in this chain.
  • Context: Securitization agreement (likely a change of name/merger from SunTrust Bank to Truist Bank).

Timeline diagram

timeline
    title Ownership of US 11318227
    2018 : Inventors to Lifenet Health
    2019 : Security Interest to SunTrust Bank
    2021 : Security Interest to Truist Bank
    2022 : Issued

NPE / troll-pattern signals

1. Shell-entity transfer — not present. The assignees are operating companies or financial institutions.
2. Known asserter in the chain — not present. No known NPEs are identified in the assignment chain.
3. Repeat correspondent across the chain — present. BASS, BERRY & SIMS PLC appears as the correspondent for both the 2019-06-10 (Reel 049339/0471) and 2021-04-02 (Reel 053070/0676) security interest recordings.
4. Cascading transfers — not present. The transfers involve the original operating company and financial institutions.
5. Pre-litigation transfer — unclear. While the Google Patents record indicates litigation filed in Virginia Eastern District Court in 2023, the provided assignment data does not include transfers immediately preceding this date.
6. Bankruptcy fire-sale — not present. Lifenet Health appears to be an active, operating company.
7. Privateering — not present. No evidence suggests a privateering arrangement.
8. Defensive aggregator (anti-NPE) — not present. The patent has not been assigned to a defensive aggregator.

Verdict

Insufficient data. While there is a repeat correspondent in the chain (Bass, Berry & Sims PLC for the security interests in Reel 049339/0471 and Reel 053070/0676), the core assignments are from inventors to an operating company and then security interests to financial institutions. There is no clear evidence of a transfer to a licensing-only shell entity or a known NPE, nor a cascading transfer pattern indicating a troll. Further, the litigation mentioned in Google Patents does not have corresponding assignment records in the provided data to suggest a pre-litigation transfer for assertion purposes.

USPTO Assignment Center search page: https://assignmentcenter.uspto.gov/

To identify the most relevant prior art for US Patent 11318227, I will examine the references cited by the patent itself. The priority date for US11318227 is March 14, 2013. Therefore, any patent or publication with an effective date prior to March 14, 2013, can be considered prior art under 35 U.S.C. § 102.

Since the prompt instructs me to refer to the provided "Full patent text (authoritative; prefer this over search results when they conflict)", and also instructs me to "Search the USPTO database for the specific patent number 11318227", and the provided text itself contains references to the Google Patents page, I will use the references listed on the Google Patents page for US11318227 (https://patents.google.com/patent/US11318227/en) as the authoritative list of cited prior art.

Due to the extensive number of prior art citations for US11318227 (over 1000 US patents), presenting a comprehensive analysis for each would be impractical and exceed typical analytical scope. I will identify the most relevant prior art by focusing on patents and publications that are explicitly mentioned within the "DETAILED DESCRIPTION OF THE INVENTION" section of US11318227 as being incorporated by reference for specific technical aspects that are central to the claimed invention. These incorporated references are often highly relevant as they form part of the background knowledge explicitly relied upon by the applicant.

Additionally, I will also look at the earliest dated patents in the "U.S. Patent Documents" list that appear highly relevant to the core concepts of "aligned fibers" and "electrospinning" to ensure a broad review of the most pertinent prior art.

Claims of US11318227 (as per Google Patents):

The claims of US11318227 are:

1. A scaffold comprising an electrospun fiber, wherein a fast Fourier transform (FFT) analysis result of the fiber has adjacent major peaks with about 180° apart from each other, and wherein the fiber comprises heart basement membrane extract, heart basement membrane extracellular matrix, placenta basement membrane extract, or placenta basement membrane extracellular matrix.
2. The scaffold of claim 1, wherein the fiber comprises heart basement membrane extract.
3. The scaffold of claim 1, wherein the fiber comprises placenta basement membrane extract.
4. The scaffold of claim 1, wherein the fiber has an average diameter of about 1000 nm or less.
5. The scaffold of claim 1, wherein the fiber has an average diameter of about 500 nm or less.
6. The scaffold of claim 1, further comprising a support.
7. The scaffold of claim 6, wherein the fiber is attached to and/or covers the support.
8. The scaffold of claim 1, which is in a form of an elongated sheet or a composite of multiple layers of sheets.
9. The scaffold of claim 8, wherein the electrospun fiber is aligned in one direction.
10. The scaffold of claim 9, wherein the electrospun fiber is aligned in a direction parallel or perpendicular to the length of the elongated sheet or the multiple layers.
11. The scaffold of claim 8, which is prepared by folding or rolling the sheet or sheets, along with the direction of the electrospun fiber alignment to form an elongated roll implant.
12. A method of promoting nerve repair, the method comprising implanting the scaffold of claim 1 into a nerve damaged site of a subject in need thereof.
13. The method of claim 12, further comprising culturing dorsal root ganglia or stem cells on the scaffold prior to the implanting.
14. A method of promoting differentiation of stem cells into osteoblasts, chondrocytes, ligament cells or tendon cells, the method comprising culturing the stem cells on the scaffold of claim 1 in conditions suitable for the stem cell differentiation.
15. The method of claim 14, wherein the differentiation is into osteoblasts.
16. The method of claim 14, wherein the differentiation is into chondrocytes.
17. The method of claim 14, wherein the differentiation is into ligament cells or tendon cells.
18. An electrospinning apparatus comprising:
    (i) at least one spinneret comprising an electrified tip; and
    (ii) a collector comprising two rods and a platform connected to the two rods, wherein the two rods are configured to split an electric field between them.
19. The apparatus of claim 18, wherein the two rods are configured to rotate.
20. The apparatus of claim 18, further comprising a control mechanism configured to control the electric potential of the electrified tip.
21. The apparatus of claim 18, wherein the platform comprises a bearing having mercury.
22. The apparatus of claim 18, wherein the collector is biocompatible.
23. An electrospinning apparatus comprising:
    (i) two spinnerets, each of which comprises a tip electrified with an opposite charge to one another; and
    (ii) a collector comprising two rods and a platform connecting the two rods, wherein the two rods are grounded.
24. A method of electrospinning an aligned fiber, the method comprising:
    (i) extruding a solution from an electrified tip of a spinneret; and
    (ii) collecting the extruded solution on at least a part of a collector comprising two rods and a platform connected to the two rods, wherein the two rods are configured to split an electric field between them.
25. The method of claim 24, wherein the two rods are configured to rotate.
26. The method of claim 24, further comprising applying a bioactive factor to the solution.
27. The method of claim 26, wherein the bioactive factor comprises a bone morphogenetic protein (BMP).
28. The method of claim 24, wherein the solution comprises heart basement membrane extract, heart basement membrane extracellular matrix, placenta basement membrane extract, or placenta basement membrane extracellular matrix.
29. A method of electrospinning an aligned fiber, the method comprising:
    (i) extruding one or more solutions from electrified tips of two spinnerets, each of which comprises at least one tip electrified with an opposite charge to a tip of the other spinnerets; and
    (ii) collecting the extruded solution on a part of a collector comprising two rods and a platform connecting the two rods, wherein the two rods are grounded.
30. The method of claim 29, further comprising applying a bioactive factor to the solution.
31. The method of claim 30, wherein the bioactive factor comprises a bone morphogenetic protein (BMP).
32. The method of claim 29, wherein the solution comprises heart basement membrane extract, heart basement membrane extracellular matrix, placenta basement membrane extract, or placenta basement membrane extracellular matrix.

Most Relevant Prior Art for US11318227

Based on the explicit references cited within the description of US11318227 and a review of the extensive list of cited U.S. Patents, the following represent some of the most relevant prior art documents. The priority date of US11318227 is March 14, 2013.

1. Publications explicitly incorporated by reference within the specification of US11318227:

• Full Citation: Ayres C E, Jha B S, Meredith H, Bowman J R, Bowlin G L, Henderson S C, Simpson D G. "Measuring fiber alignment in electrospun scaffolds: a user's guide to the 2 D fast Fourier transform approach", J Biomater Sci Polym Ed. 2008; 19(5):603-21.

  • Publication/Filing Date: 2008
  • Brief Description: This publication describes methods for measuring fiber alignment in electrospun scaffolds using a 2D fast Fourier transform (FFT) approach. The patent references this work for how FFT analysis may be performed to measure fiber alignment.
  • Potential Anticipation (35 U.S.C. § 102): This publication directly teaches the use of FFT analysis to characterize fiber alignment in electrospun scaffolds. Claims 1-3, 8-11, 14-17, 24, 25, 28-32, which rely on or describe an "aligned fiber" or a scaffold where "a fast Fourier transform (FFT) analysis result of the fiber has adjacent major peaks with about 180° apart from each other," could be anticipated or rendered obvious by this reference, particularly regarding the method of characterizing alignment. This paper describes the characterization, but not necessarily the specific materials or the electrospinning apparatus used to achieve the alignment as claimed.

• Full Citation: U.S. Patent No. 6,189,537 to Bell et al.

  • Publication/Filing Date: February 20, 2001
  • Brief Description: This patent describes demineralized matrices and methods of making them. US11318227 refers to this patent for demineralized matrices.
  • Potential Anticipation (35 U.S.C. § 102): Claims related to a "biocompatible matrix derived from natural sources that has been optionally cleaned, disinfected, chemically modified, decellularized, particulated, homogenized, lyophilized, gamma ray irradiated, and/or plasticized" or "demineralized matrices" (mentioned in the description but not directly in the main claims as a specific feature of the aligned fiber or scaffold itself, but rather as a type of matrix that can be coated). Specifically, if the electrospun fiber were coated on a demineralized bone matrix, this patent could anticipate aspects of the matrix itself as described in the specification for supporting the electrospun fibers. For example, if claim 6 or 7's "support" or "biocompatible matrix" were interpreted broadly to include demineralized bone, this could be relevant. Claims related to methods of preparing bone matrix solutions, or using such solutions, could also be relevant if this patent describes relevant solutions.

• Full Citation: U.S. Patent No. 6,305,379 to Bell et al.

  • Publication/Filing Date: October 23, 2001
  • Brief Description: Similar to US6189537, this patent also describes demineralized matrices and methods for their preparation. US11318227 refers to this patent for demineralized matrices.
  • Potential Anticipation (35 U.S.C. § 102): Similar to US6189537, this patent could anticipate aspects of a demineralized biocompatible matrix if used as a support for the claimed electrospun fibers. This would potentially impact claims 6 and 7, and the general teaching of coating matrices as described in the specification, if those matrices are demineralized.

• Full Citation: PCT/US2011/49192 (International Application No.)

  • Publication/Filing Date: August 25, 2011 (International Filing Date)
  • Brief Description: This PCT application describes methods for preparing heart basement membrane extract and/or heart basement membrane extracellular matrix. US11318227 explicitly mentions this application as describing the preparation methods for these materials.
  • Potential Anticipation (35 U.S.C. § 102): This application is highly relevant

Based on the analysis of US Patent 11318227 (US'227) and the prior art references cited on its Google Patents page, the following combinations of prior art would render the claims obvious under 35 U.S.C. § 103 as of the priority date of March 14, 2013. A person having ordinary skill in the art (POSITA) would have been motivated to combine these references due to the predictable nature of electrospinning, the known desire for aligned scaffolds in tissue engineering, and the common practice of characterizing materials.

The core inventive concepts of US'227, as outlined in its Summary and Detailed Description, include:

1. A scaffold comprising an aligned fiber, particularly electrospun fibers, with alignment quantifiable by a Fast Fourier Transform (FFT) analysis showing adjacent major peaks about 180° apart.
2. An electrospinning apparatus configured to produce aligned fibers, specifically one with a collector comprising two rods and a platform, wherein the rods split an electric field, or an apparatus with two spinnerets having oppositely charged tips and a collector with two grounded rods.
3. Methods of electrospinning or preparing electrospun fibers using the described apparatus.
4. Methods of culturing cells (e.g., stem cells, dorsal root ganglia) on such scaffolds and promoting their differentiation into specific cell types (e.g., osteoblasts, chondrocytes, ligament, tendon) or promoting nerve repair.
5. Methods of coating a biocompatible matrix with such aligned electrospun fibers.

Obviousness Argument 1: Aligned Electrospun Fiber Scaffolds with Quantifiable Alignment

Combination: US20100280624A1 in combination with Ayres et al. (2008).

• US20100280624A1 (published November 4, 2010, prior to US'227's priority date) explicitly discloses "Aligned electrospun scaffold, use of same for culturing cells, and methods of promoting differentiation of cells." This patent teaches the fundamental concept of an electrospun scaffold where the fibers are aligned. Similar disclosures can be found in US20120078358A1 (published March 29, 2012), US20130071477A1 (published March 21, 2013), and US20130071478A1 (published March 21, 2013), all predating the US'227 priority date. These references establish the prior art's knowledge of producing and utilizing scaffolds with aligned electrospun fibers.
• Ayres et al. (2008) ("Measuring fiber alignment in electrospun scaffolds: a user's guide to the 2 D fast Fourier transform approach," J Biomater Sci Polym Ed. 2008; 19(5):603-21) (published 2008, prior to US'227's priority date) provides a detailed methodology for characterizing and quantifying fiber alignment in electrospun scaffolds using Fast Fourier Transform (FFT) analysis. The patent itself references this publication as a method for performing FFT analysis. The FFT analysis result showing "adjacent major peaks with about 180° apart" is a direct and predictable mathematical representation of a well-aligned linear fibrous structure, as acknowledged in US'227's description.

Motivation to Combine: A POSITA seeking to develop or improve aligned electrospun scaffolds, as taught by US20100280624A1, would naturally need a reliable method to quantify the degree of fiber alignment. Ayres et al. (2008) presents a well-established and publicly available method (FFT analysis) for precisely this purpose. It would be a routine matter for a POSITA to apply a known analytical technique to characterize a known material (aligned electrospun fibers). The characterization method does not impart novelty to the scaffold itself, but rather provides a way to describe an existing property.

Conclusion: Claims relating to a scaffold comprising aligned electrospun fibers, particularly when characterized by FFT analysis showing adjacent major peaks about 180° apart, would have been obvious given the combination of prior art disclosing such scaffolds and methods for their quantitative characterization.

Obviousness Argument 2: Electrospinning Apparatus for Aligned Fiber Production

Combination: US8227236B2 in combination with general knowledge of electrospinning apparatus from references such as US7364687B2, US5470392A, and the principles of electric field manipulation for fiber alignment.

• US8227236B2 (granted July 24, 2012, prior to US'227's priority date) describes "Systems and methods for forming an aligned nanofiber scaffold." This reference establishes the prior art's knowledge of electrospinning systems specifically designed to produce aligned nanofibers.
• US7364687B2 (granted April 29, 2008, prior to US'227's priority date) teaches a general "Electrospinning apparatus." Numerous other patents like US5470392A (1995), US6312521B1 (2001), US6569201B2 (2003), US7122046B2 (2006), US7651634B2 (2010), and US8337894B2 (2012) also detail various electrospinning apparatus and processes, including components like spinnerets, collectors, and high voltage power supplies. These references show that the basic components and principles of electrospinning were well-known.
• The concept of manipulating electric fields and collector geometries to control fiber distribution, diameter, and alignment is explicitly stated as known in the background of US'227 itself: "Polymer solution properties, applied electrical potential, polymer molecular weight, polymer solution flow rate, distance between spinner and collector, ambient parameters (e.g. humidity, air velocity, temperature) and motion of the collecting target can be altered to form fibers of controlled fiber distribution, diameter and alignment via electrospinning." This includes using charged collectors or multiple electrodes. The idea of using grounded collectors with oppositely charged spinnerets to neutralize fiber charges and enhance collection thickness is also described in US'227 as a modification of a known process, implying it was within the general knowledge of the art.

Motivation to Combine: A POSITA, motivated by the desire to produce aligned electrospun fibers (as taught by US8227236B2 and others), would routinely experiment with and optimize electrospinning apparatus configurations to achieve or improve fiber alignment. Given the known ability to alter electrical potential and collector design to control alignment, developing a collector with two charged rods to "split an electric field" (as depicted in FIG. 1A/1D of US'227) or using grounded rods with oppositely charged spinnerets would be a predictable design choice to guide and collect charged fibers. These are recognized engineering approaches for manipulating electrostatic fields in electrospinning to achieve desired fiber deposition patterns, including alignment.

Conclusion: The various electrospinning apparatus claims, particularly those related to specific collector configurations for generating aligned fibers, would have been obvious to a POSITA by combining existing electrospinning technologies with the known principles of electric field manipulation for fiber guidance, in light of the prevalent demand for aligned scaffolds.

Obviousness Argument 3: Methods of Culturing Cells and Promoting Differentiation on Aligned Electrospun Scaffolds

Combination: US20100280624A1 in combination with US20080287955A1 and general knowledge in tissue engineering.

• US20100280624A1 (published November 4, 2010) explicitly teaches "Aligned electrospun scaffold, use of same for culturing cells, and methods of promoting differentiation of cells." This directly covers the general claims for culturing cells and promoting their differentiation on such scaffolds. Specific differentiation pathways (osteoinductive, chondroinductive, ligament/tendon differentiation) are also explicitly taught in this and similar applications like US20120078358A1, US20130071477A1, and US20130071478A1.
• US20080287955A1 (published November 13, 2008) further specifically discloses a "Nerve guide comprising aligned electrospun fibers," demonstrating the application of aligned electrospun scaffolds for nerve repair.

Motivation to Combine: The field of tissue engineering has a long-standing motivation to use biocompatible scaffolds to support cell growth, proliferation, and differentiation for repairing damaged tissues. The prior art (e.g., US20100280624A1) clearly teaches that aligned electrospun scaffolds are beneficial for these purposes, including promoting differentiation into bone, cartilage, ligament, and tendon cells. For nerve repair, US20080287955A1 shows the specific utility of aligned electrospun fibers as nerve guides. A POSITA would be motivated to apply these known aligned scaffolds for their demonstrated therapeutic benefits, using various cell types (including stem cells and dorsal root ganglia, which are commonly used in tissue engineering research) to achieve known outcomes (osteogenesis, chondrogenesis, ligament/tendon genesis, nerve repair). The materials specified in US'227 (e.g., collagen, ECM, PCL) are also well-known in prior art for tissue engineering scaffolds (e.g., US8007788B2, US8178129B2).

Conclusion: The methods of culturing cells on aligned electrospun scaffolds and promoting their differentiation or nerve repair would have been obvious to a POSITA, as these applications are directly taught and motivated by existing prior art in tissue engineering using such scaffolds.

Obviousness Argument 4: Coating a Biocompatible Matrix with Electrospun Fibers

Combination: Any electrospinning method patent (e.g., US20090226487A1) in combination with a patent disclosing biocompatible matrices (e.g., US6432437B1 or US8007788B2) and the understanding of using electrospinning for coating.

• US20090226487A1 (published September 10, 2009) describes "Electrospinning method[s]," encompassing the general process of extruding a solution and collecting it as fibers. The concept of collecting electrospun fibers directly onto a target substrate (matrix) acting as a collector is a common and fundamental application of electrospinning.
• US6432437B1 (granted August 13, 2002) discloses a "Tissue engineering scaffold," and many other references (e.g., US8007788B2, US8124409B2, and the extensive list of tissue engineering scaffolds) describe various biocompatible matrices (bone, cartilage, synthetic polymers, ECM, etc.) and their forms (particulates, sheets, blocks) for use in implants.

Motivation to Combine: A POSITA in the field of medical implants and tissue engineering would be motivated to enhance the properties of existing biocompatible matrices by coating them with aligned electrospun fibers. This approach could provide a more favorable surface for cell attachment, proliferation, and guided tissue regeneration. Given the known electrospinning methods and the availability of various biocompatible matrices, it would be an obvious design choice to adapt an electrospinning apparatus (potentially one already configured for alignment) to deposit fibers directly onto a pre-existing matrix, thereby forming a coated implant. The patent itself mentions the collector "may comprise a bone matrix, and the electrospun fiber is collected on the surface of the bone matrix, resulting in coating of the bone matrix." This indicates that using a matrix as a collector was understood.

Conclusion: The methods of coating a biocompatible matrix with electrospun fibers using an electrospinning apparatus would be obvious to a POSITA seeking to create advanced composite tissue engineering constructs with improved regenerative properties.