BioXclude™ Technology Presentation
BioXclude™ Technology Presentation
Amnion-Chorion
• Avascular tissue comprising the inner most layer of placenta separating the mother and fetus
Adapted from Boyd (1970)
Adapted from: Niknejad, H et, al.European Cells and Materials 2008; 15:88-99
Amniotic fluid
Maternal decidua
Layer Extracellular Matrix Composition
Amnion
Epithelium
Basement Membrane Collagen types III, IV, V; laminin, fibronectin, nidogen
Compact layer Collagen types I, III, V, VI; fibronectin
Fibroblast layer Collagen types I, III, VI; nidogen, laminin, fibronectin
Intermediate (spongy) layer
Collagen type I, III, IV; proteoglycans
Chorion
Reticular layer Collagen types I, III, IV, V, VI; proteoglycans
Basement Membrane Collagen types VI; fibronectin, laminin
Trophoblasts
Amniotic Tissue
Procurement - Placenta obtained from consenting
donor during elective caesarian section.
- Compliance with AATB and FDA allograft tissue standards.
Purion™ Processing Technology - First used in ophthalmology (2006)- Today used to treat chronic wounds, plastics, sports medicine, and many others- Cleanses and maintains delicate tissue structure - Dehydrates and embosses graft- Terminally sterilized (10-6 SAL)- Retains active growth factors, cytokines, and extracellular matrix architecture
Tissue Processing and Procurement
Benefits of Combined Amnion-Chorion Allograft
•BioXclude is the only product in thedental market with combined Amnion-Chorion
•BioXclude contains 4 to 5x more growthfactors than amnion only allografts
•Chorion layer accounts for over 80% ofthe growth factors found in BioXclude
•BioXclude is 4 to 5x thicker than amnion onlyallografts
IHC Analysis of Amnion Chorion and Porcine Membranes 1
* Significant difference vs. porcine** No significant difference vs. porcine
FGF = Fibroblast Growth FactorTGFβ = Transforming Growth Factor BetaPDGFα = Platelet-Derived Growth Factor AlphaPDGFβ = Platelet-Derived Growth Factor Beta
Laminin Laminin-5 TGFβ FGF PDGFα PDGFβ
Amnion Chorion(BioXclude, n=5)
4.4 ± 0.55 (p<0.001)*
4.2 ± 0.45(p<0.001)*
1.4 ± 0.9(p<0.05)*
0.7 ± 0.45(p<0.05)*
2.4 ± 0.55(p<0.005)*
3.2 ± 1.1(NS)**
Porcine Collagen(BioGide®, n=5)
0.0 0.0 0.0 0.0 0.0 3.0 ± 0.0
0.0
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4.2 ± 0.45
BioXclude Porcine
Laminin-5
Xenoudi P and Lucas M. IADR Meeting, Abstract #146797. San Diego, CA. March 16-19 2011University of Colorado School of Dental Medicine, Advanced Periodontal Therapies
PR061312v01
Purion® Processing Retains Biological Properties
Scientific Attributes of Amniotic Tissue
Literature Review - 2009― Reviewed over 150 papers (27 met inclusion criteria)― Findings: Possesses four unique attributes
(1) Immunoprivileged ― No foreign body inflammatory response― No reported adverse events ever reported
(2) Anti-Inflammatory ― Modulates inflammation: decreased patient pain― Downregulates inflammatory cell recruitment
(3) Anti-Bacterial ― Reduces risk of infection ― Tight seal formed after placement precludes bacteria
(4) Accelerates Healing― Cytokines / Growth Factors (PDGF, VEGF, FGF…) ― Cell adhesion proteins (fibronectin, laminin, laminin-5…)
Chen E, Tofe A. J Implant Adv Dent 2009; 2(3):67-75.
Courtesy of MiMedx Group
Presented at ER
42 Days postop
PR081301v01
Chronic Wound (use not in dental, GF potential) 2
10 Days postop debridement
Case Overview• Preop wound size was 18.75cm2; amputation
scheduled; Epifix® was last resort.• 30% wound area reduction at 7 days• Additional 15% area reduction at 14 days• Additional application at 14 days• Wound closed at 28 days.• At 3 months, patient is walking with custom
molded show.
Retains Biological Factors- Growth factors - Cell adhesion proteins- Interleukins - Tissue inhibitors of metalloproteinases
Cellular Activity - Migration of human
mesenchymal stem cells in-vitro - Recruitment of mesenchymal
progenitor stem cells in-vivo
Koob T et al. Int Wound J 2013; Online:1-8AmnioFix Scientific and Clinical Compendium, March 2013. MiMedx Group
Purion Processing Technology 3
Non-Dental Trade Names - EpiFix™ (wound care) - AmnioFix™ (sports medicine)- Many others
Cytokine FreshPurion
ProcessedPDGF-AA PDGF-BB TGF-a TGF-b bFGF EGF VEGF IL-10 IL-4 PIGF TIMP-1 TIMP-2 TIMP-4
Cytokines Present in Amnion/Chorion Tissue
PR081306v02
#30 Pre-Op 1 week
2 week 4 week 18 week
Post-Op
Courtesy of Barton Foutz, DDS, Henderson, CO
Site Preservation without Flap Elevation or Primary Closure
Post-Op
Post-Op
Tooth #3 BX in Place* Site Closure
96 Hours 10 Days 3 Months
Holtzclaw D, Toscano N. J Implant Adv Clin Dent 2011; 2(6):49-55
* Grafted FDBA
Site Preservation 4
PR061316v01
Osseous Defect BioXclude Folded Over Itself* Site Closure
3 Months Implant Placement Pre-Op / 3 Month Post-Op
Courtesy of Dan Holtzclaw, DDS, MS, Austin TX
PR071302v02
Site Preservation (Moderate Buccal Defect) 5
* Site grafted with FDBA
Defect on #19 Site Closure* 10 Days
8 Weeks 3 Months
* Second piece of BioXclude was placed over the top covering crest and lingual aspect
PR061323v02
Site Preservation (Moderate Buccal Defect) 6
Courtesy of Dan Holtzclaw, DDS, MS, Austin TX
Excellent Tissue Profile
Buccal Dehiscence Defect Extraction Socket BioXclude Over FDBA
Non-Primary Closure 3 Months Pre-Op / 3 Mo Post-Op
Courtesy of Dan Holtzclaw, DDS, MS, Austin TX
Site Preservation (Small Buccal Defect)
Haroon Ashraf DDS, Kerri Font DDS,MS, Michael Schurr PhD, Mark Lucas DDS,MS, Charles Powell DDS,MS
University of Colorado School of Dental Medicine Postgraduate PeriodonticsABSTRACT Materials
Conclusion
Purpose: In surgical procedures, the selection of adjunctive biomaterials may amplify the innate regenerative potential within a wound and enhance the clinical outcome. The purpose of this study is to evaluate wound biomodification by assessing antimicrobial properties present within a human derived composite amnion-chorionmembrane (ACM).
Material & Methods: Membranes analyzed in the study were the human ACM BioXclude™ (SnoasisMedical) and the porcine derived collagen membrane BioGide® (Geistlich). Paper discs were used as a positive control along with paper discs containing tetracycline (TCN) at a minimum bactericidal concentration (MBC) of 62 µg/mL as a negative control. Three bacterial species were used in the study: Aggregatibacteractinomycetemcomitans (A.a.), Streptococcus mutans (S.m.), and Streptococcus oralis (S.o.).
The same number of colony forming units per milliliter (CFU/mL) for each bacterial species was inoculated on each membrane and control discs. Samples were grown over brain heart infusion (BHI) agar medium under optimal conditions. Discs from each group were removed at 12 and 24 hours and sonicated to remove the bacteria off the membranes. A serial dilution was performed to quantify bacterial growth in triplicate by counting the CFU/mL present. A Wilcoxon signed-rank test was performed to compare any differences between growths.
Results: Three in vitro trials were conducted. TheACM inhibited growth at all time points, with allbacterial strains, identical to the negative controlTCN discs. The collagen membrane and positivepaper controls did not inhibit growth of any of thebacterial species throughout the 24-hour studyperiod.
Bacterial Growth
It was determined that the ACM was as bactericidal as paper discs inoculated with TCN at its MBC. The collagen membrane does not appear to have anti-microbial properties due to its support of the bacterial growth similar to the positive control discs.
IN VITRO ANALYSIS OF ANTIMICROBIAL ACTIVITY BETWEEN AN AMNION-CHORION MEMBRANE AS COMPARED TO A COLLAGEN
MEMBRANE
Abstract # 2523349
0.7BioXclude - FGF (40x)
2.4BioXclude - PDGFα (40x)
Median Microbial Count
4.2 ± 0.45 0 ± 0
3.0 ± 03.2 ±1.1
Allograft Amnion Chorion Porcine Collagen0 ± 04.4 ± 0.55
Figure 1. Bacterial growth following removal of attempted A.a. culture from ACM (left half of plate) and collagen membrane (right half of plate) at 24 hours following serial dilution. P < 0.05 for microbial growth on ACM and negative control vs. either
collagen membrane or positive control.
Figure 2: Median microbial count for each membrane and bacteria at 12 hours.
Figure 3: Median microbial count for each membrane and bacteria at 24 hours.
BioXclude left exposed at site closure
1 week postop 1 month postop Final Abutment connection at 6 weeks
Absence of keratinized tissue
Courtesy of Nicola De Angelis, DDS, MS, University of Genoa, Italy
Keratinized Tissue Augmentation
BioXclude adapted around implants
Tooth #14 BioXclude Exposed* 2 Weeks
10 Weeks Restored (15 Months) Restored (15 Months)
* Grafted with FDBA
Courtesy of Muyeenul Hassan, BDSIndiana University School of Dentistry, Graduate Periodontics
PR061320v01
Site Preservation (heavy smoker) 7
Courtesy of Paul Rosen, DMD, MSYardley, PA
Extraction Socket with Bone Loss 15
Pre-Op 2 Weeks (BX Dehiscence) 5 Weeks
5 Months5 Months 5 Months
• Full maxilla flap reflection followed by scaling and root planning and osseous contouring.
• BioXclude placed over only one side the exposed bone.
• Reattachment measured by force needed to pull suture separating the gingiva.
Holtzclaw D et al. J Imp Adv Clin Dent 2102; 4(5); 19-25
Tensile Strength (in grams) Required to Separate Gingival Flap
72 hours 1 week 2 weeks 3 weeks
Control (nothing) 200 350 1,600 2,100*
BioXclude side 325 1,700 2000* 2,200** Sutures pulled through without flap displacement
PR061315v01
Aids in Formation of Clinical Attachment 37
Pre-Op BioXclude Placement Site Closure
Implants @ 4 months* 6 Months** 10 Months
Childers G. Retrieved from http://www.snoasismedical.com. May 2012
* 7.5 mm increase in ridge width (5.5 mm → 13 mm)** Increase zone of attached gingiva and partial root coverage on tooth #21
Ridge Split 25
PR061333v01
Overview - Single site (private practice) - 12 months results - 64 consecutive patients, 78 sites- Average age = 57 years (range 34-92)- 14 smokers, 2 oral bisphosphonates,
1 rheumatoid arthritis
Results - No adverse effects - Excellent early healing- PD: Pre = 8.5 mm, Post = 3.4 mm- CAL: Pre = 9.0 mm, Post = 4.4 mm- PD Improvement: 5.1 mm - CAL Improvement: 4.6 mm
Holtzclaw D, Toscano N, Clinical Advances in Periodontics. 2013; 3 (3): 131-137
PR061329v02
Clinical Study - Guided Tissue Regeneration 12
Pre-Op #30 Grafted with FDBADefect
BioXclude Placed Dry BioXclude Hydrated
Probing Depth Pre-Op = 12 mm 3 Months = 3 mm
16 Month Post-Op
PR061327v01
Guided Tissue Regeneration 35
Courtesy of Dan Holtzclaw, DDS, MS, Austin TX
Grade III Furcation Buccal BioXclude Over Bone Graft* Grade III Furcation Lingual
Site Closure Buccal 6 Month Post-Op
* Grafted with Osteocel and rhPDGF
Pre-Op / 6 Mo Post-Op
PR061347v02
Rosen, P . Clinical Advances in Periodontics. 2013; 3 (2): 64-69
Guided Tissue Regeneration 29
Pre-op radiograph BioXclude over FDBA
Site closure 1 week post-op 4 month radiograph
Missing buccal wall
PR031402v01
Courtesy of Muyeenul Hassan, BDS, MS, Univ of Detroit Mercy School of Dentistry
Sinus Lift Membrane Perforation Repair 23
Sinus membrane perforation
BioXclude™ Placement BioXclude™ adheres to the sinus membrane and seals perforation
Lateral sinus window covered with BioXclude™
Bone allograft placement into sinus cavity
Courtesy of Dan Holtzclaw, DDS, MSAustin, TX
Pre-Op CBCT Perforated Sinus Placed BioXclude
Sinus Packed w/ Bone Placed Sinus 4 Month CBCT
PR061338v01
Courtesy of Dan Holtzclaw, DDS, MS, Austin TX
Sinus Perforation and Elevation 24
Failed implant removal Bone graft placement
BioXclude placement Post-op view Reentry
Implant placement
PR101301v01
Courtesy of Robert Miller, DDS, MS, Austin TX
Immediate Implant 13
Immediate Implant
Placement Around Implants Intentionally Left Exposed
Placed Over Implant Treads 1 Year Post-Restoration
Courtesy of Dan Cullum, DDS (Coeur D Alene, ID)
#18 Extracted, #19 Edentulous
Pre-Op Implant #20 Defect
BioXclude in Place* 12 Month Post-Op 12 Month Radiograph
Pre-Op Radiograph
* Grafted with Accell Bone Putty
Implant Repair 29
Courtesy of Dan Holtzclaw, DDS, MS, Austin TX
PR061330v01
Buccal defect Bone graft placement
BioXclude placement Post-op view Reentry
Implant placement
PR031401v01
Courtesy of Robert Miller, DMD, Plantation, FL
Immediate Implant (Moderate Facial Defect) 14
Extraction #8 and #9 FDBA placed
Untrimmed BioXclude placed Bone has grown over seated implants at 5 month reentry,
Placement of healing abutments
Deep V shaped defects present after implant placement
PR021501v01
Courtesy of Robert J Miller, DMD, Plantation, FL
Immediate Implant 22
Pre-Op Placement of BioXclude
10 Days Post-OP Implants at 3 Months Final Restoration
Grafted w/FDBA
* 4.2 mm increase in ridge width at site #28 (2.3 mm → 6.5 mm) 4 mm increase in ridge width at site #29 (4.5 mm → 8.5 mm)
Holtzclaw D, Toscano N. J Implant Adv Clin Dent 2012; 4(2):25-37
Ridge Split 32
PR061331v01
Extraction #23-26, Tenting Screws Placed
Collagen Membrane PlacedGrafted with FDBA
BioXclude Placement Site Closure*
PR061346v02
* Vestibular dissection into the chin was performed to close the site.
Double Membrane - GBR 26
Courtesy of Dan Holtzclaw, DDS, MS, Austin TX
Healing at 21 Days
Defect at #10 Block Graft* BX over Grafted Area
10 Days Post-Op Re-Entry at 7.5 Months Pre-Op and 11 Months
* Grafted with Cancellous Allograft Block and FDBA
Block Graft 19
PR061334v01
Wang V. Retrieved from http://www.snoasismedical.com. January 2013
Missing Palatal Bone BioXclude Placement* Site Closure (note gingival cleft)
48 Hours Post-Op 10 Days Post-Op Pre-Op 6 Months* Placed over rhBMP-2 + Collagen Sponge and Titanium Mesh
PR061335v01
Courtesy of Dan Holtzclaw, DDS, MS, Austin TX
rhBMP-2 and Titanium 17
Atrophic anterior maxilla
BioXclude placed over Ti; site closure
8 month healing Mesh removed at 10 months, implants placed*
CBCT scans at preop and 10 months
rh-BMP2 is placed underneath Ti mesh
PR021502v02
Courtesy of Dan Holtzclaw, DDS, MS, Austin, TX
Ridge Augmentation with rhBMP-2 and Ti 20
Healing abutments placed after 4 months
At 10 days incision line epithelialized over
* All exposed threads are grafted with Maxxeus 70/30 allograft blend and BioXclude
Allograft Block and Particulate* BioXclude Placed Over ePTFE
Site Closure 2 Week Post-Op Pre-op CBCT
* Both block graft and cortical/cancellous particulate are contain allogenic stem cells
PR091303v01
Courtesy of Paul Petrungaro, DDS, Chicago, IL
GBR with ePTFE and Block Graft 21
Edentulous Site with Ext #24, 25
4 Month Post-op
82 year old female with OAF, post extraction #3
CBCT view Defect exposed
Defect covered with buccal fat pad and then BioXclude
Buccal flap advanced with primary closure
6 week postop
PR051501v01
Courtesy of Erica Shook, DDS, University of the Pacific, Dugoni School of Dentistry, Dept of Oral & Maxillofacial Surgery, San Francisco, CA
Oroantral Fistula (OAF) Closure 18
Extracted #18 and #19
Non-primary closure 14 week re-entry Implants placed
Allograft blend placed
PR051401v01
Courtesy of Dan Holtzclaw, DDS, MS, Austin, TX
Double Extraction Site Preservation 8
BioXclude placed
Parabiosis Model Stem Cell Recruitment In Vivo
• Tissue samples taken at 3, 7, 14 and 28 days.
Villeda S. et al 2014
Mann et al. J Surg Res, 2015
dhACM
Sham
Control ADM
GFP
• Implanted dHACMs recruited significantly more progenitor cells compared with controls (*P < 0.05) and displayed in vivo SDF-1 expression with incorporation of CD34, CD90 and CD31 + progenitor cells within the matrix.
Courtesy of MiMedx Group
EpiFix® placed
PR081302v01
Healing with Reduced Scar Tissue 36
Day 1 Week 2 Week 3 Week 4 10 Months
Overview - Randomized, controlled, split month study- 9 patients, 22 sites- Sites grafted with Maxxeus FDBA; covered
with either ACM (BioXclude) or d-PTFE- Membranes left intentionally exposed
Results at 3 Months Postoperative- Statistically significant greater bone volume
measured by micro CT (55.1% vs 39.7%) - Statistically significant less post-op pain on
days 1 and 2- Radiographic increase in ridge height (slight
loss in height for d-PTFE) - Less radiological ridge width resorption
Hassan, M, Blanchard S, Prakasam, S. AAP Poster Presentation. Sept 19-22, 2014, San Francisco, CA. University of Indiaana, Department of Periodontics
PR041501v01
Clinical Study – Site Preservation 38
PR061344v01
Thank You!