WO2020101689A1 - Matériels et procédés de réparation de nerfs au moyen de greffons nerveux d'origine animale - Google Patents

Matériels et procédés de réparation de nerfs au moyen de greffons nerveux d'origine animale Download PDF

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Publication number
WO2020101689A1
WO2020101689A1 PCT/US2018/061309 US2018061309W WO2020101689A1 WO 2020101689 A1 WO2020101689 A1 WO 2020101689A1 US 2018061309 W US2018061309 W US 2018061309W WO 2020101689 A1 WO2020101689 A1 WO 2020101689A1
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Prior art keywords
nerve
breast
neurotization
nerves
grafts
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PCT/US2018/061309
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English (en)
Inventor
Ivica DUCIC
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Axogen Corporation
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Priority to CA3119782A priority Critical patent/CA3119782A1/fr
Priority to PCT/US2018/061309 priority patent/WO2020101689A1/fr
Priority to AU2018449641A priority patent/AU2018449641B2/en
Priority to CN201880099569.4A priority patent/CN113056294A/zh
Priority to KR1020217014775A priority patent/KR102406052B1/ko
Priority to JP2021526233A priority patent/JP2022507364A/ja
Priority to EP18939894.4A priority patent/EP3880262A4/fr
Priority to IL283079A priority patent/IL283079B2/en
Publication of WO2020101689A1 publication Critical patent/WO2020101689A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3641—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the site of application in the body
    • A61L27/3675—Nerve tissue, e.g. brain, spinal cord, nerves, dura mater
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; 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
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/32—Materials or treatment for tissue regeneration for nerve reconstruction

Definitions

  • MRC Medical Research Council
  • SO no sensory recovery
  • SI recovery of deep cutaneous pain
  • S2 is return of some superficial cutaneous pain and some degree of tactile sensibility
  • S3 is return of superficial cutaneous pain and tactile sensibility without over response
  • S3+ is return of superficial cutaneous pain and tactile sensibility with some 2-point discrimination recovery
  • S4 is complete sensory recovery.
  • the scale has been used to measure meaningful recovery which in some studies has been a defined as S3 and above. Secondly, it was noted that neurotization only required 10 to 15 additional minutes of operative time.
  • Autograft harvest involves harvesting autogenous nerves from abdominal sites and implanting the nerves into the recipient patient’s breast tissue.
  • Autograft harvest based breast neurotization requires longer operation room procedures and increased risk of muscle denervation. Muscle denervation causes laxity, loss of muscle tone, poor aesthetic outcome, and increased risk of incisional hernia.
  • Autograft harvest also involves loss of regenerative capacity because half of nerve diameter goes to muscle and produces dead ends. Therefore, surgical methods that avoid problems associated with autograft harvest based breast neurotization are desirable.
  • the invention provides a standardized and reproducible surgical procedures, and related materials, that allow for conservation of the innervation to the rectus abdominis while allowing for neurotization of the flap.
  • the nerve allograft is used as a novel bridging material in breast neurotization, which overcomes shortcomings of direct coaptation, conduit, or autograft applications, and reflects on connector-assisted nerve coaptation facilitating the nerve repair.
  • the subject invention provides materials and methods for performing breast neurotization with nerve grafts in breast surgeries, such as reconstructive breast surgery.
  • the methods of the invention mitigate risks of conventional surgical methods and provide alternative approaches and mitigation plans.
  • Figure 1 shows key anatomical landmarks for DIEP flap breast neurotization. Outlines of DIEP abdominal flap and post-mastectomy chest wall defect. Essential nerves (ICN1, ICN2, ICN3, ICN10, ICN11, ICN12), vascular structures (medial and lateral DIEA, internal mammary artery and vein), and bony landmarks (ribs I, II, III) are shown.
  • Essential nerves ICN1, ICN2, ICN3, ICN10, ICN11, ICN12
  • vascular structures medial and lateral DIEA, internal mammary artery and vein
  • bony landmarks ribs I, II, III
  • Figure 2A shows DIEP flap dissection in standard lateral to medial fashion. Schematic demonstrating typical positions of distal ends of the sensory components of respective intercostal nerves and expected incision of rectus sheath lateral to intercostal nerves.
  • Figure 2B shows intraoperative DIEP flap dissection with emphasis at the lateral raw perforators and lateral rectus border.
  • Figure 3A shows exposure of the ICNs after the incision of anterior rectus sheath and longitudinal rectus muscle fibers spread. Schematic representation of the retrograde dissection of sensory component of the intercostal nerves (yellow) until joining the motor components (green) at an intramuscular sensory-motor Y junction. If medial row perforators were dominant and used for flap supply, lateral anterior rectus sheet fascial opening and rectus spread might be limited only to allow sensory ICN harvest.
  • Figure 3B shows intraoperative view of a dissected sensory ICN component as marked by the tip of the forceps.
  • Figure 4A shows separation of sensory component of ICN11, just distal to Y-j unction with preserved motor component. Schematic showing resulting sensory nerve pedicle (yellow) and preserved motor component (green) with longitudinally dissected rectus muscle.
  • Figure 4B shows intraoperative picture showing resultant sensory nerve pedicle to be used for neurotization.
  • Figure 5 shows dissection approach to third rib cartilage. Schematic showing the resulting defect following mastectomy, pectoralis major muscle is longitudinally spread and the perichondrium is incised and separated circumferentially, in preparation for the third rib cartilage for removal. Dashed vertical line is sternum.
  • Figure 6A shows schematic drawing showing internal mammary artery and vein after removal of the cartilage. ICN3 is available for use after careful separation from third rib cartilage and perichondrium.
  • Figure 6B shows anatomical specimen dissection identifying ICN3 in its location along the inferior third rib cartilage.
  • Figure 6C shows schematic showing ICN2 exposed by careful dissection from perichondrium and the inferior border of second rib cartilage if dual innervation with ICN3 is desired.
  • Figure 6D shows specimen dissection identifying ICN2 in its location.
  • FIG. 7A shows vascular anastomosis of flap DIEA/DIEV to internal mammary artery and vein. 7A. Schematic showing internal mammary artery and vein are dissected and separated inferiorly, which was then anastomosed to the DIEP flap perforators. Yellow marked flap available donor nerves are sensory ICN11 and ICN12, while recipient chest nerves are INC2 and ICN3.
  • Figure 7B shows intraoperative view of connected flap and chest vessels, and dissected ICN3 in preparation for nerve reconstruction.
  • Figure 8 A shows bridging of donor nerves to recipient nerves with processed human nerve allograft. Schematic showing tension free single nerve neurotization with ICN11 and ICN3 with coaptation of the nerve facilitated by translucent porcine intestinal submucosa nerve connector, as alternative to direct suture.
  • Figure 8B shows specimen illustration of single nerve breast neurotization.
  • Figure 8C shows schematic showing tension free dual nerve neurotization with ICN11 and ICN12 connected to ICN2 and ICN3, respectively.
  • Figure 8D shows specimen illustration of dual nerve breast neurotization.
  • Figure 9A shows traditional dissection and separation of donor intercostal nerve. Schematic showing the donor pedicle that consists of both sensory (yellow) and motor (green) components that were dissected out of the rectus abdominis muscle (original position of pedicle illustrated by dashed yellow line).
  • Figure 9B shows intraoperative picture of traditional dissection of donor intercostal nerve that contains both sensory and motor components.
  • the invention provides surgical methods for implanting autogenous or allogeneic nerves into a patient’s breast. Such implantation induces breast neurotization of the breast tissue in the patient that has undergone or is undergoing a breast surgery, such as mastectomy or breast reconstruction surgery.
  • the methods provided herein allow for neurotization of the entire breast tissue flap via an autogenous or allogeneic nerve graft.
  • the methods comprise implanting nerve tubes, including synthetic nerve tubes, allogeneic nerves, or autogenous nerves into breast flap.
  • Deep inferior epigastric perforator (DIEP) flap breast reconstructions have been known to have limited return of sensation at the recipient site, and potentially cause abdominal bulge and wall weakness at the donor site.
  • Breast neurotization or reinnervation of reconstructed breast flaps have been shown to have protective effects against mechanical or thermal injuries as well as positive effects on a patient’s quality of life.
  • simultaneous breast neurotization of the flap area is yet to be a standardized component in breast reconstruction procedures after mastectomies.
  • current clinical breast neurotization data point to the lack of a standardized operative approach, a standard nerve gap bridging medium, and a paucity in homogenous data for clinical sensory recovery outcomes.
  • certain embodiments of the invention provide surgical techniques that minimize abdominal wall morbidities, provide a standardized breast neurotization technique, and increase the chances of meaningful sensory recovery by utilizing the human processed nerve allograft as the preferred nerve gap bridging material.
  • This operative technique is unique in the use of the nerve allograft for breast neurotization and selective use of only the sensory component of the flap, while preserving the rectus abdominis motor innervation.
  • Processed nerve allografts have been shown in clinical studies to be effective in bridging gap lengths up to 70 mm, with superior meaningful sensory recovery outcomes compared to hollow tube nerve conduits, and comparable to nerve autografts without the additional operative morbidities.
  • the surgical methods of the invention can be customized to enable single or dual nerve breast neurotization and this novel approach performs favorably compared to conduit or autograft neurotization.
  • the materials and methods of the subject invention enable surgeons to apply a standardized and reproducible breast neurotization surgery, further optimizing chances of meaningful sensory recovery.
  • Breast neurotization is an important component of breast reconstruction.
  • the invention demonstrates the importance of taking only the sensory branch and preserving the motor branch at the donor site. This selectivity prevents aberrant nerve regeneration of the recipient sensory nerve into a blind motor stump thus optimizing sensory outcomes. This also provides anatomical justification for why sensation recovery in the autograft-neurotized breasts is less than expected.
  • the invention provides standardized breast neurotization during breast reconstruction, minimized abdominal wall related morbidities, and improved meaningful sensory recovery and thus quality of life in breast reconstruction patients.
  • the invention provides a surgical method for breast neurotization.
  • the method comprises implanting an allogeneic or autologous nerve to the patient’s breast flap.
  • the allogeneic or autologous nerve is obtained from an intercostal nerve (ICN), particularly, ICN10, ICN11, or ICN12.
  • ICN intercostal nerve
  • an allogeneic or autologous ICN10, ICN11, or ICN12 is harvested and implanted to the patient’s ICN2 or ICN3.
  • an allogeneic or autologous nerve from ICN10, ICN11, and ICN12 is harvested and implanted to one of the patient’s ICN2 or ICN3.
  • ICN10 or ICN11 can be harvested and implanted to ICN2 or ICN3.
  • ICN11 or ICN12 can be harvested and implanted to ICN2 or ICN3. Certain such embodiments are described in Figures 12 and 13.
  • two nerves from ICN10, ICN11, or ICN12 are harvested and implanted to the patient’s ICN2 and ICN3.
  • two nerves from ICN10, ICN11, and ICN12 are harvested and each is implanted to one of the patient’s ICN2 and ICN3.
  • ICN10 and ICN11 can be harvested and implanted to ICN2 and ICN3, respectively.
  • ICN11 and ICN12 can be harvested and implanted to ICN2 and ICN3, respectively. Certain such embodiments are described in Figures 12 and 13.
  • only the sensory portion of the nerve ICN10, ICN11, or ICN12 is harvested and implanted in the sensory portion of the nerve ICN2 or ICN3. In certain such embodiments, only the sensory portions of two of the nerves ICN10, ICN11, and ICN12 are harvested and each is implanted in the sensory portion of the nerve ICN2 or ICN3.
  • processed nerve allograft is used as the bridging material in implantation of the donor nerve.
  • nerve tubes can be used as the bridging material in the implantation of the donor nerve.
  • the nerve tubes or processed nerve allografts used in certain embodiments of the invention can contain neurotrophic growth factors that stimulate nerve regeneration. Inclusion of such growth factors facilitates innervation of the flap tissue.
  • growth factors include brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), neurotrophic factor (NGF), neutrophin-3 (NT-3), ciliary neurotrophic factor (CNTF), and leukemia inhibitory factor (LIF).
  • nerve regeneration tubes are described in the United States Patents 9,687,592; 9,108,042; 9,017,714; 8,741,328; 8,632,844; 8,603,512; 7,842,304; 7,615,063; 7,135,040; 6,589,257; 6,090,117; 5,656,605; and 4,778,467. Each of these patents is incorporated herein by reference in its entirety.
  • the set comprises at least two nerve grafts are prepared from ICN10, ICN11, and ICN12 obtained from one donor.
  • the set comprises at least two nerve grafts prepared from ICN10, ICN11, and ICN12 obtained from different donors.
  • a set of nerve grafts disclosed herein can be used in a suitable surgery, for example, breast neurotization surgery described herein.
  • a set of nerve grafts may be prepared from one or more intercostal nerves that are obtained from one or more animal sources.
  • animal sources may generally include non-ruminants in addition to ruminants such as, but not limited to, sheep, cows, horses, pigs, goats, etc. It will be appreciated that other animals may be sources of a set of nerve grafts for use in humans or animals, as appropriate. It will also be appreciated that nerve grafts prepared from one or more intercostal nerves obtained from one or more animal sources may be used in surgical techniques akin to those described herein.
  • the surgical techniques described herein may be utilized depending on the graft source (e.g., human, animal, etc.) and on the graft recipient (e.g., human, animal, etc.). It will also be appreciated that such animal-sourced grafts may be used as xenografts in the breast neurotization techniques described herein in humans, or may be used (as xenografts, allografts or autografts) in reconstruction of intercostal nerve defects in animals. In some implementations, the at least two nerve grafts may be prepared from at least two different ICNs obtained from a single animal source.
  • a single animal source may comprise a single animal (e.g., one sheep) or multiple animals (e.g., multiple sheep).
  • the at least two nerve grafts may be prepared from at least two different ICNs obtained from different animal sources.
  • Different animal sources may comprise multiple different animals (e.g., a sheep and a pig, or two different species of sheep).
  • a set of nerve grafts may be prepared from one or more nerves that are obtained from one or more animal sources, including from those animal sources described above.
  • Such grafts may be used as xenografts in the reconstruction of nerve defects in humans, or may be used as xenografts, allografts or autografts in the reconstruction of nerve defects in animals.
  • Each of the nerve grafts in the set of nerve grafts of the invention can be processed to prepare nerve grafts suitable for implantation in a recipient.
  • Certain techniques of processing nerves to produce nerve grafts are described in United States Patents 9,572,911; 9,402,868; 7,851,447; and 6,972,168. Each of these patents is incorporated herein by reference in its entirety. Definitions:
  • An autologous graft is an organ, a tissue, or a part thereof obtained from a first site from a subject for implantation to a second site in the subject.
  • An allogeneic graft is an organ, a tissue, or a part thereof obtained from a first individual for implantation to a second individual of the same species as the first individual.
  • Neurotization refers to re-innervation of nerves in a portion of a body that has lost its innervation through irreparable damage to its nerve. Neurotization does not require a complete return of the sensation, sensory, or motor properties of the portion of the body that lost its innervation.
  • Preoperative markings were made with the patient standing.
  • the patient is subsequently brought to the operating room and placed in supine position with bilateral arms abducted.
  • the abdominal flap ( Figure 1) is dissected in a standard lateral to medial fashion until lateral row perforators and associated intercostal nerves are exposed ( Figures 2A-2B).
  • the anterior rectus sheath is incised craniocaudally along the lateral row perforators to expose the rectus abdominis muscle, lateral perforator vessels, and intercostal nerves (ICN) 11 and ICN12 ( Figures 3A-3B).
  • the motor component is preserved to prevent denervation of the rectus abdominis muscle.
  • the motor preservation is performed even when the lateral perforators are chosen as the dominant vascular supply. This is accomplished by harvesting the sensory component just distal to the sensory-motor Y-junction, leaving the motor innervation to the lateral rectus abdominis muscle intact ( Figures 4A-B).
  • ICNs The inclusion of one or two ICNs depends on whether a single or dual innervation of the flap is desired. Once sensory ICN branch(es) are dissected and divided, the remainder of the DIEP flap vascular dissection is completed, leaving the flap perfused until chest dissection is complete.
  • the pectoralis major muscle fibers are longitudinally split over the third costal cartilage to expose the perichondrium of the third rib.
  • the perichondrium is incised and subperichondrial dissection performed, followed by the removal of the third costal cartilage.
  • the posterior perichondrium is carefully incised and a lateral-to-medial dissection is performed until the internal mammary vessels are visualized (Figure 5).
  • the ICN3 runs along the inferior border of third rib ( Figures 6A-6B). Once identified under the perichondrium and along the inferior rib border, it is preserved, traced medially, then divided, and reflected laterally for subsequent nerve coaptation. If dual innervation is desired, then the ICN2 can be found within the upper pole of the surgical field, under the perichondrium, just inferior to and along the second rib border ( Figures 6C-6D).
  • the flap is then disconnected from the donor-site and brought to the chest.
  • Microsurgical arterial and venous anastomosis is performed in standard fashion ( Figures 7A- 7B).
  • the nerve coaptation is performed using a 1 -2mm x 50 or 1 -2mm x 70 processed human nerve allograft ( Avance ® Nerve Graft, AxoGen, Alachua FL) to bridge the gap.
  • interposing nerve allograft is then microsurgically connected to chest recipient and flap donor nerve ends via direct suture, alternatively, proximal and distal coaptation can be facilitated with a translucent and porous porcine intestinal submucosa nerve connector ( AxoGuard Nerve Connector, AxoGen, Alachua FL) ( Figure 8A,B).
  • the flap is then inset and the abdominal donor site closed in standard fashion, thus, completing the neurotized DIEP flap breast reconstruction.
  • Homogeneity of a surgical approach is critical to reliably comment on the efficacy of a procedure or a procedural concept such as breast neurotization.
  • establishing a standardized surgical technique is important to facilitate future homogenous comparative analysis.
  • a clear understanding of the principles of nerve surgery as well as expertise regarding the characteristics of available reconstructive choices like nerve conduits, autografts, and processed nerve allografts are critical for successful execution of this proposed procedure.
  • Standard treatment of nerve injuries consists of tensionless primary repair whenever possible. However, if primary repair is not possible, then bridging materials are utilized, which include nerve autografts, tube conduits, and processed nerve allografts.
  • the nerve gap encountered with breast neurotization typically measures between 50 to 70 mm, thus, far exceeding the length that is recommended for reconstruction with nerve conduits.
  • nerve autografts have traditionally been preferred when reconstructing extremity nerve defects, they are associated with donor-site complications including additional incisions, wound healing issues, painful neuroma formation, or bulge/incisional hernias if rectus muscle is denervated.
  • Processed nerve allograft is an extracellular matrix (ECM) scaffolding created from donated human peripheral nerve tissue that has been decellularized, pre-degenerated, and sterilized, which results in a cell-free microstmctural architecture with the protein composition of nerve tissue.
  • ECM extracellular matrix
  • the resultant allograft is composed of bundles of endoneurial microtubes, contained within the original nerve’s fascicle and epineurial scaffold, which is comprised of ECM proteins (laminin, fibronectin, and glycosaminoglycans) that provide natural axonal growth cues for guided regrowth, otherwise not found in hollow tube conduits.
  • ECM proteins laminin, fibronectin, and glycosaminoglycans
  • the first critical element of the donor site dissection depends on identification and perseveration of the donor intercostal nerves.
  • Cadaveric studies have found that the rectus abdominis is innervated by nerves from the rectus sheath plexus that run parallel with the most lateral branch of the DIEA before running with arterial perforators into the rectus abdominis and anterior abdominal wall.
  • the lateral branch of the DIEA and lateral row perforators are intimately related to the intercostal nerves that innervate the rectus abdominis muscle and any damage incurred to these structures during DIEP flap harvest would contribute to the previously mentioned donor-site morbidity of abdominal wall weakness, abdominal bulge, or hernia.
  • DIEP flap aims to overcome TRAM (transversus rectus abdominis muscle) flap shortcomings, the reported incidence of abdominal bulge or incisional hernia occurrence after a DIEP flap is still 3-5%. By conserving the motor component of the lateral intercostal nerves to the lateral rectus, abdominal wall morbidity should be minimized even further.
  • ICN11 and/or ICN12 are proposed.
  • the cutaneous sensory nerves will be followed proximally in a retrograde fashion to the Y- junction where it joins the motor component before continuing proximally as a mixed nerve.
  • the sensory component is harvested at the Y-j unction, fully preserving the motor branches going into the lateral rectus abdominis.
  • the pure sensory nerve pedicle is relatively short and therefore, a processed nerve allograft can be used if necessary to bridge the gap ( Figures 8).
  • This approach is suggested to provide a proper anatomical platform aiming to optimize the chances of neurotization and meaningful recovery, while also fully preserving rectus abdominis innervation.
  • ICN3 is the recipient nerve of choice, but ICN2 can also be reliably found in the anterior chest within the same surgical field.
  • the processed nerve allograft overcomes the short nerve pedicle from the DIEP flap and allows for a tension-free nerve coaptation.
  • the lateral ICN4 can be used along the anterior axillary line.
  • ICN4 can be used with the internal mammary vascular system, because there are two pivoting points, one vascular medially, and the other nerve laterally, which might affect the extent of flap rotation and inset.
  • erogenous nipple/areola sensory innervation is primarily carried by the lateral branches of ICN4 and the implications of using a nerve with these functions for breast neurotization at this time is not well understood.
  • ICN4 is used to neurotize the entire breast flap, then there may be sequelae related to overstimulation. Taking this into consideration, as well as the fact that lateral branches of ICN4 are usually transected at the level of the chest wall musculature in the process of mastectomy, these branches are mostly unavailable for neurotization, unless specifically dissected and preserved before or during the mastectomy.
  • ICN4 may not be preferred as a dominant recipient for breast neurotization.
  • connector-assisted microsurgical coaptation of the interposing nerve allograft between the flap donor and chest recipient nerves may facilitate growth across the coaptation site without fascicular misalignment or undue axonal escape.
  • the surgical methods of the invention revolutionize breast reconstruction by offering a reliable, reproducible, and effective neurotization procedure.

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Abstract

La présente invention concerne des matériaux, notamment des ensembles de greffons nerveux, qui permettent d'exécuter une neurotisation mammaire au moyen de nerfs de xénogreffe au cours d'interventions chirurgicales mammaires, telles qu'une intervention chirurgicale mammaire reconstructive. Certains modes de réalisation de l'ensemble de greffons nerveux comprennent au moins deux greffons nerveux préparés à partir d'un ou de plusieurs nerfs, tels qu'un ou plusieurs nerfs intercostaux (ICN), obtenus auprès d'une ou de plusieurs sources animales. De tels greffons nerveux de sources animales peuvent être utilisés en tant que xénogreffes dans la reconstruction de défauts nerveux chez les êtres humains, et, en particulier, les greffons ICN de sources animales peuvent être utilisés comme xénogreffes dans la reconstruction de défauts de nerfs ICN chez les êtres humains, notamment par l'utilisation de la technique de neurotisation du sein décrite par les présentes. Les greffons nerveux de sources animales peuvent également être utilisés dans la reconstruction de défauts nerveux chez des receveurs animaux, en tant que xénogreffes, allogreffes et autogreffes.
PCT/US2018/061309 2018-11-15 2018-11-15 Matériels et procédés de réparation de nerfs au moyen de greffons nerveux d'origine animale WO2020101689A1 (fr)

Priority Applications (8)

Application Number Priority Date Filing Date Title
CA3119782A CA3119782A1 (fr) 2018-11-15 2018-11-15 Materiels et procedes de reparation de nerfs au moyen de greffons nerveux d'origine animale
PCT/US2018/061309 WO2020101689A1 (fr) 2018-11-15 2018-11-15 Matériels et procédés de réparation de nerfs au moyen de greffons nerveux d'origine animale
AU2018449641A AU2018449641B2 (en) 2018-11-15 2018-11-15 Materials and methods for nerve repair with animal-sourced nerve grafts
CN201880099569.4A CN113056294A (zh) 2018-11-15 2018-11-15 使用动物来源神经移植物的神经修复所用的材料及方法
KR1020217014775A KR102406052B1 (ko) 2018-11-15 2018-11-15 동물 기원 신경 이식편으로 신경을 수복하기 위한 재료 및 방법
JP2021526233A JP2022507364A (ja) 2018-11-15 2018-11-15 動物由来の神経移植片を用いた神経修復のための材料および方法
EP18939894.4A EP3880262A4 (fr) 2018-11-15 2018-11-15 Matériels et procédés de réparation de nerfs au moyen de greffons nerveux d'origine animale
IL283079A IL283079B2 (en) 2018-11-15 2018-11-15 Materials and methods for nerve repair with nerve grafts of animal origin

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EP3880262A4 (fr) 2022-07-20
IL283079B1 (en) 2023-09-01
IL283079A (en) 2021-06-30
KR102406052B1 (ko) 2022-06-07
AU2018449641B2 (en) 2023-11-30
AU2018449641A1 (en) 2021-06-03
CN113056294A (zh) 2021-06-29
IL283079B2 (en) 2024-01-01

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