BioRenew ª Placental Tissue Matrix Therapy ª · BioRenew ª PTM Therapy Physician FAQ 1. WhatÕs the difference between PX50 & DX100? PX50¨ is a highly concentrated, ready-to-use

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The Power of the Body.The Innovation of Science.®

Placental Tissue Matrix Therapy™

BioRenew™

Table ofContents

Talk to yourpatients aboutBioRenew™ Placental TissueMatrix Therapyp. 3-4

skyebiologics.com

Patient Marketing Guide

Patient FAQ

Physician FAQ

Product Information

HydraTek® Process

Dosing Protocol

Order Form

Technique Guide

Resources

What is Regenerative Medicine?Regenerative medicine is a leading medical field that combines the latest scientific research and medical technology, with a focus on non-surgical treatment of damaged tissue found in tendons, ligaments, inflamed tissue, degenerated joints and other painful conditions.

Regenerative medicine utilizes the potential of cells, growth factors, and other biologic components to support and enhance the body’s natural repair process. These treatments may reverse the effects of traumatic injury, chronic pain, or wear and tear due to age or overuse.

Where is Regenerative Medicine Typically Used?

Regenerative medicine treatments may be very successful in reducing pain and inflammation, repairing injuries, restoring joints, rejuvenating soft tissues, and improving overall quality of life. Treatments are available for many anti-aging, cosmetic, neurological, pain management, sports medicine and orthopaedic conditions.

Common musculoskeletal conditions treated with regenerative medicine include: inflammation, osteoarthritis, joint pain, tennis elbow, plantar fasciitis, tendinitis and tendinosis, tendon and ligament tears, muscle strains, bursitis, runner’s knee, hip pain, back and neck pain.

What is Skye® BioRenew™ PTM Therapy?

BioRenew™ Placental Tissue Matrix (PTM) Therapy™ is an all-natural treatment that utilizes powerful Growth Factors, Collagens, Extracellular Proteins and Bioactive Molecules naturally found in human placental tissues.1-2 These placental tissue components may provide your body with the foundation it needs to reduce inflammation, restore tissue, reduce scarring, and alleviate pain.3-5

How does it Work?

BioRenew™ PTM Therapy is applied directly to the area of injured or damaged tissue. This biologic treatment replaces the body’s missing ‘connective tissue matrix’, which is a natural interconnected system of Collagens, Growth Factors, and Bioactive Molecules that provide the structure, integrity and replenishment of the body’s various tissues.6-7

Where do Skye® BioRenew™ PTM Therapy products come from?

BioRenew™ products are derived from human placental tissues, donated by volunteer donors after a live healthy C-section delivery. All donors are U.S based. Processing is performed by Skye® Biologics at our AATB accredited facility.

BioRenew™PTM TherapyPatientMarketing Guide

3MRK 025 REV B, NOVEMBER 2015. Copyright © 2015 Skye® Biologics, Inc. All rights reserved. 1-7 References on file with Skye Biologics.

Skye Biologics I 2629 Manhattan Beach Blvd, Redondo Beach, CA 90278 I 310.796.5680 I skyebiologics.com

2. How is the treatment performed?BioRenew™ PTM Therapy can be performed in a doctor’s office. The physician may use a local anesthetic or other methods to numb the area, and the product is applied directly to the injured or damaged connective tissue.

3. What should I expect following treatment? Most patients only require a single treatment to achieve significant results. Patients may experience pain relief as soon as 3-10 days after treatment, and continued improvement over the following weeks and months.

4. How does this compare to other treatments (PRP, Adipose Stem Cells, or Bone Marrow Aspirate)?BioRenew™ PTM Therapy is provided in flowable form, and is applied using minimally invasive technique. No patient blood draw or tissue harvesting is required. BioRenew™ PTM Therapy provides a complete biologic solution with Growth Factors, Collagens, Extracellular Proteins, and Bioactive Molecules.2-3

5. Is this an alternative to surgery? BioRenew™ PTM Therapy contains biologic components that may control inflammation,4 and may help support the restoration of damaged tissues5 so surgery may not required. While surgery is necessary for certain injuries and conditions, it is more invasive, can cause trauma to the body, and often results in significant pain during recovery and longer heal times.

6. How does the physician know where to apply the product?Physicians can accurately target the area based on a review of your diagnostics, along with the use of manual touch, video-fluoroscopy or ultrasound guidance.

7. How long does treatment take?BioRenew™ PTM Therapy is typically a single one-time treatment, not a series. The procedure only takes 5-10 minutes, and your entire visit will typically take approximately 30 minutes.

8. What is the post-treatment care?Always follow the advice of your physician. Typically, no immobilization, bracing or other inconvenient post-treatment care is required. Physician may prescribe off-loading, immobilization, or protected active rehabilitation.

9. What is the recovery time?No sedation is necessary, so patients are able to walk out on their own after appropriate monitoring.

10. Does my health insurance cover treatment using BioRenew™ PTM Therapy?Like many regenerative medicine procedures, BioRenew™ PTM Therapy procedures are considered elective or non-covered by insurance providers.

BioRenew™ PTM TherapyPatient FAQ

1. How do I know if BioRenew™ PTM Therapy is right for me?

BioRenew™ PTM Therapy has been reported to be effective in the clinical treatment of various conditions.1 Consult your physician to determine if BioRenew™ PTM therapy is right for your condition.



BioRenew™PTM TherapyPhysicianFAQ

1. What’s the difference betweenPX50 & DX100?

PX50® is a highly concentrated, ready-to-use biologic formulated for common painful weekend warrior conditions. PX50® is available in 0.5cc and 1.0cc volumes.

DX100® is a premium formulation, for more complex and interventional pain conditions. DX100® is available in 1.0cc, 1.5cc and 2.0cc volumes.

2. Is there an advantage between the frozen and room temperature products?Skye® BioRenew™ products are available in both cryopreserved and ambient temperature versions. Cryopreservation is the historical standard for long term storage. Skye® HydraTek® Process developed a market-first room temperature product, The Original Ambient Flowable Tissue Matrix™ through its unique preservation technology, for improved ease of storage, handling and application.

3. What are common conditions these products are used to treat? Common musculoskeletal conditions treated with regenerative medicine include: inflammation, osteoarthritis, joint pain, tennis elbow, plantar fasciitis, tendinitis and tendinosis, tendon and ligament tears, muscle strains, bursitis, runner’s knee, hip pain, back and neck pain. Visit biorenewtherapy.com for more information on common conditions.

4. How much product can I apply?A dosing protocol is available for reference on treating common conditions. Physicians may apply a larger dose of product at their discretion. There is no contraindication for the amount of product used per treatment, or for reapplication.

5. Are there any contraindications?The product should not be implanted in the presence of active infection. Certain antibiotic residuals may remain in the tissue. Package inserts (IFUs) are available at skyebiologics.com/resources.

6. You recommend mixing with sterile saline, do I have to?No. The product may be used straight out of the vial without mixing. However, many conditions being are easier to treat effectively with a larger total amount of fluid, so the products can be extended with sterile saline to the desired volume. Mixing instructions are provided on our application technique guide, available at skyebiologics.com/resources.

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8. Do these products cause an immune response?BioRenew™ PTM Therapy products are created using placental tissues and components, which are considered ‘immune privileged’,1 and cause little to no response in the patient. As a results, no graft matching or blood typing is required.

9. Have there been any adverse reactions?No adverse clinical reactions to Skye® Biologics placental tissue matrix products have been reported.

10. How common are BioRenew™ PTM Therapy procedures?Skye® Biologics has produced tens of thousands of units to date, for use around the country.

11. What is the recovery time?Depending on the condition, patients are typically reporting reduced pain symptoms just days after treatment. Improvement may commonly be noticed 3-10 days post treatment, and continue to improve over the coming weeks and months. In tendon and ligament treatment, continued improvement and remodelling has been tracked to the 6 month mark.2

12. Do all patients respond the same? No. While most patients report significant improvement shortly after treatment, occasionally patients may see improvement start at 4-8 weeks post treatment. Patients with extensive medical histories may notice less improvement. Factors such as compliance, co-morbidity, diet, activity, lifestyle, or re-injury may affect outcomes.

13. What should I charge patients for treatment?Each physician’s patient base may vary. For reference on pricing around the country, please contact Skye® Biologics, and ask for ‘BioRenew™ Therapy Account Support’.

14. Is there a code to bill insurance for the product?No. These products, like many regenerative medicine treatments, are considered elective, and are not covered by insurance. The products are charged ‘cash-pay’ to the patient, or included in the total cost of treatment to the patient.

15. Is there a CPT code for the procedure?Various procedure codes are available for common pain management procedures, which may be applicable. For a reference list of procedure codes, please contact Skye® Biologics, and ask for ‘BioRenew™ Therapy Account Support’.

BioRenew™ PTM TherapyPhysician FAQ

7. What other fluids can I mix the product with?

Skye®recommends to mix with sterile saline. At their discretion, physicians may mix with an anesthetic or other fluids such as adipose tissue, bone marrow aspirate, or PRP. Skye does not validate the efficacy of any other therapeutic agents.



These in-office treatments contain the complete placental connective tissue matrix, including:

• Collagens1

• Growth Factors2

• Extracellular Proteins3

• Bioactive Molecules4

BioRenew™ PTM TherapyIn-Office Pain & Sports Med Products

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PX50®

Placental Tissue Matrix

Flowable tissue matrix formulated for common pain management conditions.

Product Sizes: 0.5cc, 1.0cc

DX100®

Placental Tissue Matrix

Flowable tissue matrix formulated for complex and interventional pain conditions.

Product Sizes: 1.0cc, 1.5cc and 2.0cc

INDICATION

Skye® Biologics human placental connective tissue matrix is intended for homologous use to replace or supplement damaged or inadequate connective tissue.5

Minimally manipulated biologic allografts are regulated by the U.S. Food and Drug Administration (FDA) as Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps), under Section 361 of the PHS Act.6

Ready To Use FluidNo thawing or hydration required.

Cryopreserved VersionThe historic standard for preservation.

Room Temperature VersionThe only product of it’s kind in market. For improved storage and handling.

Non-ImmunogenicChorion-free. Created using only immune-privileged components that induce little or no immune response.

1Single, One-Time TreatmentDoesn’t require a repeat or series treatment.

No Invasive Blood or Tissue Draw Unlike PRP, Adipose Cells, or Bone Marrow Cells.

5 Year Shelf LifeFor all cryopreserved and ambient products.

Safety & QualityHydraTek® Process removes antigens, and is proven to preserve both the biological viability and biomechanical integrity.

PX50® & DX100®

HydraTek® Process Advantage

THE DIFFERENCE IS IN THE PROCESS

HydraTek® Process has developed a series of industry-first products, including:

The Original Flowable Connective Tissue Matrix™ and The Original Ambient

Flowable Tissue Matrix™.

HydraTek® has been shown to preserve a majority of the natural

collagens found in unprocessed placental tissues,7 and contain a higher

concentration of more growth factors than leading competitors.8

Growth Factors Preserved by the HydraTek® Process8

Fibroblast

bFGF

Epidermal

EGF

Keratinocyte

KGF

Platelet- Derived AA

PDGF -AA

Platelet- Derived BB

PDGF-BB

Placental

PIGF

Transforming -β1

TGF -b1

Transforming -β2

TGF -b2

Transforming -β3

TGF -b3

Vascular endothelial

VEGF

Extracellular Proteins and Bioactive Molecules of Placental Tissues9-12

Collagen Hyaluronan Fibronectin Laminins

COL HA FIB LAM

Tissue Inhibitors of Metalloproteinases

TIMP-1 TIMP-2 TIMP-4

Interleukin-10Interleukin-4

IL-04 IL-10

Milligrams(mg)

Leading Competitor 1

Leading Competitor 2

HydraTek® PX50®

HydraTek® DX100®

Biologic Content Per Vial – Comparison of Sports Med Products13

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PX50® & DX100®

Dosing Protocol

Common Pain Management Conditions

These protocols are for reference purposes only, and suggest the minimum dosing requirements. Final dosing determination

is up to the physician. Various factors, including the size or severity of the injury, may dictate amount of graft required.

While PX50® and DX100® work well as a single dose, one-time treatment, there is no contraindication to applying a higher

volume of graft. For more robust treatment, or premium treatment option, a higher dose of graft may be applied.

PX50® and DX100® are indicated as a placental connective tissue matrix, to supplement or replace damaged or inadequate

connective tissue. In all applications, the graft should be applied appropriately into or onto the intended area of damaged

or inadequate connective tissue.

Skye®recommends to mix with sterile saline. At their discretion, physicians may mix with an anesthetic or other fluids such

as adipose tissue, bone marrow aspirate, or PRP. Skye®does not validate the efficacy of any other therapeutic agents.

Condition Total Implantable Volume Mixing Directions

Plantar Fasciitis 2.0cc total 0.5cc or 1.0cc graft, plus remainder of sterile saline

Rotator Cuff 1.5cc total 0.5cc or 1.0cc graft, plus remainder of sterile saline

Epicondylitis 1.0cc total 0.5cc graft plus 0.5cc sterile saline

Tendonopathy 1.0cc total 0.5cc graft plus 0.5cc sterile saline

Muscle Tears 1.0cc total 0.5cc graft plus 0.5cc sterile saline

Ligament Strains 1.0cc total 0.5cc graft plus 0.5cc sterile saline

Neuritis 1.0cc total 0.5cc graft plus 0.5cc sterile saline

Degenerative Disease (Can vary depending on size and level of degeneration)

Knee 2.5cc total 0.5cc or 1.0cc graft, plus remainder of sterile saline

Ankle 2.0cc total 0.5cc or 1.0cc graft, plus remainder of sterile saline

Shoulder 2.0cc total 0.5cc or 1.0cc graft, plus remainder of sterile saline

Finger / Toe 0.25cc total 0.25cc graft, or 0.125cc graft plus 0.125cc sterile saline

Facets 0.5cc total per facet 0.25cc graft plus 0.25cc saline

Sacroilliac (SI) 1.5cc total 0.5cc or 1.0cc graft, plus remainder of sterile saline

EDU 006 REV A, OCTOBER 2015. Copyright © 2015 Skye® Biologics, Inc. All rights reserved. 9


Shipping Information

Facility Name:

Shipping Contact Name:

Product Arrival Date (MM/DD/YY):

Shipping Address:

City: State: Zip:

Phone: Fax:

Email:

Billing Information

Cardholder: Card Type: Visa MC Amex

Card Number: Expiry Date:

(If preferred, please call in your credit card information to Skye Client Relations at 310-796-5680)

Billing Address:

City: State: Zip:

Phone: Fax:

Email:

Order Information

Product Volume Room Temp Frozen Price/Ea. Qty Total

PX50®0.5cc PX50 PX50P

1.0cc PX100 PX100P

DX100®

1.0cc DX100 DX100P

1.5cc DX150 DX150P

2.0cc DX200 DX200P

Shipping & Handling (For ambient temp only. Call for cryofrozen.) Total Product Charges

Standard Overnight (up to 5 units) Add $65.00 Shipping & Handling Charges

Priority Overnight (up to 5 units) Add $75.00Total Order

First AM Delivery Add $150.00

Our Client Relations team is available by phone at 310-796-5680. Orders will be filled when payment is processed.

PX50® & DX100®

In-Office Order Form

MRK 021 REV B, NOVEMBER 2015. Copyright © 2015 Skye® Biologics, Inc. All rights reserved.


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To place an order, fax to (888) 696-5662 or email to [email protected].

(If preferred, please call in your credit card information to

PX50® & DX100®

In-Office Technique Guide

EDU 005 REV C, DECEMBER 2015. Copyright © 2015 Skye® Biologics, Inc. All rights reserved. 11


Storage & Handling

Preparation & Application

72hr

+

PX50® & DX100® CRYO PRODUCT is shipped in a cryo-cooler. Shipping box must be kept room tempera-ture & sealed until use.

+

PX50® & DX100® CRYO PRODUCT containers have a 72 hour shelf life. Contact client relations if longer stor-age time is required.

+

PX50® & DX100® CRYO PRODUCT can be stored at -20°C for up to 6 months, or -40°C until the expiry date.

+

CRYO PRODUCT ONLY remove product package from cold storage 15 min prior to use to thaw.

2.

If mixing is desired*, remove cap & add sterile saline or other fluid, and replace cap.

3.

Shake vial to mix completely.

PX50® & DX100® can be stored at ambient tempera-ture until the expiry date.

1.

Using aseptic technique, peel open clear product pouch & present vial onto sterile field.

4.

Open vial & draw into syringe using 18G needle (or similar). Change to 21-23G to inject.

5.

Find and mark the injection site using manual touch, ultrasound or other guidance.

6.

Numb the site or sedate the patient as desired.

7.

Apply the graft directly to the area of damaged or inade-quate connective tissue, with small, clockwise injections.

* NOTE: Mix at up to a 2:1 ratio, depending on the preferred total injectable volume for the intended site. Product may be combined with sterile saline or other fluid. Larger volumes may need to be mixed in the syringe.

Post-Treatment

After use affix Tissue ID Label from box to the included Track-ing Card, and return to Skye client relations.

Typical post-treatment care includes immobilization & off- loading of the injured area to allow for optimal recovery.

Physicians may prescribe anti- inflammatories or other medi-cations as they see fit.

At physician’s discretion, pro-tected active rehab without immobilization or anti-inflam-matories may be prescribed.

Resources

please visitskyebiologics.com/resources

please visitbiorenewtherapy.com

For more information contact:

White PapersInstructions for Use Technique GuidesProduct Indications Certificates & Licenses

More informationon BioRenew™ PTMTherapy

MRK 025 REV A, OCTOBER 2015. Copyright © 2015 Skye® Biologics, Inc. All rights reserved. 12


310.745.3600

Documents

BioRenew ª Placental Tissue Matrix Therapy ª · BioRenew ª PTM Therapy Physician FAQ 1. WhatÕs the difference between PX50 & DX100? PX50¨ is a highly concentrated, ready-to-use