23496_Axogen_interface

biomaterial synthesis and characterization

welcome to the axogen innovation lab

bioelectronics

we are passionate about restoring nerve function and quality of life to patients with peripheral nerve injuries

histopathology image analysis

tissue processing cell culture tissue engineering

• active laminin • collagen • sugar side chains of CSPG

The peripheral nerve endoneurial tubes (tubes that house individual axons) contain the: which are involved in the molecular and cellular mechanisms of degeneration and regeneration. EndFragment

nerve anatomy

rough nerve surface

intact ECM integrity

compromised ECM integrity

used surgical scissors

trimming is a critical step to prepare the nerve ends for repair and regeneration

prevention of compression

new surgical blade #11

nerve compression

smooth nerve surface

the gap between transected nerve ends must be bridged by a delicate fibrin cable

unprocessed peripheral nerve

processed nerve allograft

high resolution imaging shows similarities between native nerve and processed nerve allograft

microarchitecture maintenance

cell removal

axogen-developed histological assays ensure the quality of every lot of processed nerve allograft

sidechain removal from CSPG

inactivated nerve tissue - limited neurite extension

neurites | green (GAP-43)

whole DRG

in vitro assays help identify the next generation of peripheral nerve repair solutions

bioactive material - organized neurites

bioactivated culture media - increased neurite outgrowth

inactive material - disorganized neurites

neurites | brown (beta III tubulin)

inactivated culture media - limited neurite outgrowth

bioactivated nerve tissue - neurite extension

normal healthy muscle

healthy normal nerve fibers

excess collagen deposition

axons: red | myelin: green

pre-clinical model development allows for exploration of peripheral nerve injuries and new solutions to help patients

normal epineurium

loss of muscle mass

injured surrounding tissue and non-transected nerve

smaller fibers: nerve injury

healthy surrounding tissue and non-transected nerve

healthy tissue

injured tissue

and drive the science of peripheral nerve repair

brand new state of the art facility in downtown Tampa

built to foster innovation and collaboration

continue the conversation with a VIP tour of R&D laboratories

allograft processing is designed to mimic wallerian degeneration

size-matched allografts provide more fascicular area than similarly sized cable autograft

cabled sural nerve autograft

native nerve to be repaired by grafting

revolutionizing the science of nerve repair®

wallerian degeneration prepares the injured nerve for regeneration

• the active laminin • collagen • sugar side chains of CSPG

effects of flexion-extension on direct repair

epineurial retraction with fasicular escape

host response to suture

epineurial suturing minimizes the impact to the regenerating axons

direct neurorrhaphy

epineurial suture placement

perineurial suture placement

epineurial tearing

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natural ECM scaffold

native nerve vs. allograft

nerve physiology: degeneration and regeneration

suturing and tension

large diameter nerve gap repair

preclinical model development

in vitro assays

DR vs. CAR

axoguard HA+ technology

trimming

axogen lab VIP tour

zone of injury

fibrin cable: nerve gap

avive+ technology

preclinical model application

quality assurance assays

avance method

biomaterial platforms

indications-contraindications

the resorbing lubricating layer reduces friction, creates a separating layer

conforms to the shape of the tissue for optimal protection

axoguard HA+ design characteristics enable remodeling and vascularization, a lubrication layer for gliding, and ideal handling

SIS membrane provides a natural scaffold that allows body to restore itself through site-specific remodeling.

translucent, allows clear visualization of underlying tissue

natural ECM scaffold

post implantation vascularization

SIS is a natural scaffold that offers long term protection through site-specific remodeling into the patient’s own tissue.

SIS membrane provides a natural scaffold that allows the body to restore itself through site-specific remodeling.

capillaries

cellular infiltration

supports vascularization and remodeling by host cells, resulting in a new tissue layer

revolutionizing the science of nerve repair®

epineurial retraction with fasicular escape

effects of flexion-extension on direct repair

zone of injury is ~ 13 mm + lost tissue

micro-computed tomography

proximal nerve end

distal nerve end

zone of injury extends into the proximal and distal nerve ends after sharp laceration with knife

scanning electron microscopy

distal nerve end

zone of injury extends into the proximal and distal nerve ends after complex laceration with circular saw

zone of injury is ~ 18 mm + lost tissue

proximal nerve end

distal nerve end

zone of injury is about ~ 13 mm + lost tissue

zone of injury is ~ 18 mm + lost tissue

zone of injury is ~ 14 mm + lost tissue

zone of injury extends into the proximal and distal nerve ends after laceration with broken glass

zone of injury is ~ 14 mm + lost tissue

small intestine submucosa (SIS) - based biomaterial

biomaterial resorption

biomaterial platform with distinct applications for nerve protection

7 days post implantation

placental-derived biomaterial

16 weeks post implantation biomaterial remodeling

trichrome staining

connector-assisted repair (CAR)

cellular debris

phagocytic cell, brown

nerve and muscle injury nerve connector

excess cellular debris

reduced cellular debris

axons, red | myelin, green

fewer myelinated neurons

myelinated neurons

in an injured tissue bed, axoguard nerve connector protects the coaptation site during critical healing period

excess phagocytic cells

direct repair (DR)

fewer phagocytic cells

bioactivated nerve tissue - neurite extension

inactive material - disorganized neurites

bioactive culture media - increased neurite outgrowth

inactivated nerve tissue - limited neurite extension

inactive culture media - limited neurite outgrowth

bioactive material - organized neurites

direct repair (DR)

reduced cellular debris

connector-assisted repair (CAR)

excess phagocytic cells

myelinated neurons

fewer myelinated neurons

fewer phagocytic cells

placental-derived soft tissue matrix designed for optimal handling suitable for nerve, tendon, and other soft tissue procedures

processing removes the trophoblast layer while maintaining amnion and chorion with no maternal components

minimally processed soft tissue matrix retains inherent properties of anmiotic tissue

epithelial cells lining the amnion layer

the orientation of the outer layers is confirmed by histological evaluation for every lot

the orientation of the multi-layer placenta-derived tissue matrix is confirmed by histological evaluation for every lot

multi-layer soft tissue matrix

illustration adapted from: Uchide et al. Mediators Inflamm. 2012; 2012: 270670.

placental tissue consists of amnion and chorion separating the maternal and fetal sides.

unprocessed peripheral nerve

processed nerve allograft

injured surrounding tissue

axons: red | myelin: green

healthy surrounding tissue

excess collagen desposition

used surgical scissors

new surgical blade #11

nerve protector

nerve injury

injury test

healthy epineurium and fascicles

cells, red collagen, blue

injury control

muscle injury

excess intraneural collagen

healthy control

minimized collagen deposition

in an injured tissue bed, axoguard HA+ acts as a physical barrier and protects the nerve

Regulatory Classification: StartFragmentAvance Nerve Graft is processed and distributed in accordance with US FDA requirements for Human Cellular and Tissue-based Products (HCT/P) under 21 CFR Part 1271 regulations, US State regulations and the guidelines of the American Association of Tissue Banks (AATB). Additionally, international regulations are followed as appropriate. Indication for Use: Avance Nerve Graft is processed nerve allograft (human) intended for the surgical repair of peripheral nerve discontinuities to support regeneration across the defect.EndFragmentStartFragment Contraindications:Avance Nerve Graft is contraindicated for use in any patient in whom soft tissue implants are contraindicated. This includes any pathology that would limit the blood supply and compromise healing or evidence of a current infection.EndFragment

Intended Use: StartFragmentAvive+ Soft Tissue Matrix is intended for use as a soft tissue barrier. The allograft may be used in numerous clinical applications, including covering the peripheral nerve to separate and protect the nerve from the surrounding environment. Rx Only The allograft is to be dispensed only by or on the order of a licensed health professional. Each allograft is intended for single-patient use. Contraindications: Avive+ Soft Tissue Matrix is contraindicated for use in any patient in whom soft tissue implants are contraindicated. This includes any pathology that would limit the blood supply and compromise healing or evidence of a current infection.EndFragment

Regulatory Classifications: StartFragment• US – Class II Medical Device – 510(k) cleared• EU – Class III Medical Device – CE Marked• UK – Class III Medical Device – CE Marked till 30th June 2028• New Zealand Wand – Class III Medical Device• Canada – Class 4 Medical Device Indication for Use: StartFragmentAxoguard Nerve Protector is indicated for the repair of peripheral nerve injuries in which there is no gap. EndFragmentContraindications: This device is derived from a porcine source and should not be used for patients with known sensitivity to porcine material. NOTE: This device is not intended for use in vascular applications.EndFragment

Regulatory Classifications: • US – Class II Medical Device – 510(k) cleared Indications for Use (US): Axoguard HA+ Nerve Protector is indicated for the management of peripheral nerve injuries where there is no gap, or following the closure of the gap. Contraindications: Axoguard HA+ Nerve Protector base membrane is derived from a porcine source and the lubricant coating is composed of sodium hyaluronate and sodium alginate. The Axoguard HA+ Nerve Protector should not be used for patients with known sensitivity to porcine, alginate, or hyaluronate materials. NOTE: This device is not intended for use in vascular applications. EndFragment

Regulatory Classifications: StartFragment• US – Class II Medical Device – 510(k) cleared• EU – Class III Medical Device – CE Marked• UK – Class III Medical Device – CE Marked till 30th June 2028• New Zealand Wand – Class III Medical Device•. Canada – Class 4 Medical Device Indications for Use (US): StartFragmentStartFragmentAxoguard Nerve Connector is intended for the repair of peripheral nerve discontinuities where gap closure can be achieved by flexion of the extremity.EndFragment Indications for Use (EU): Axoguard Nerve Connector is indicated for the repair of peripheral nerve discontinuities with gaps up to 5 mm. EndFragmentContraindications: This device is derived from a porcine source and should not be used for patients with known sensitivity to porcine material. NOTE: This device is not intended for use in vascular applications. EndFragment

Regulatory Classifications: • US – Class II Medical Device – 510(k) cleared • New Zealand – Class III Medical Device – WAND Registered Indications for Use (US): Axoguard Nerve Cap is indicated to protect a peripheral nerve end and to separate the nerve from surrounding environment to reduce the development of a symptomatic or painful neuroma. Contraindications: This device is derived from a porcine source and should not be used for patients with known sensitivity to porcine material. This device is not intended for use in vascular applications. This device is contraindicated for use in any patient for whom soft tissue implants are contraindicated; this includes any pathology that would limit the blood supply and compromise healing or evidence of a current infection. AxoguardNerve Cap should not be implanted directly under the skin. NOTE: This device is not intended for use in vascular applications. EndFragment

6 weeks post surgery

time of injury and repair

the lubricant coating helps in minimizing the potential for soft-tissue attachments.

lubricant coating, purple