The Present and Future of Biologic Materials in Surgery

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The Present and Future of Biologic Materials in
Surgery

• OVALS Conference
• 04Apr09

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Shotgun Injury

• 15 year-old male with a 20-gauge shotgun injury
• Surgically removed pellets and covered with
  Surgisis
• 14 weeks, 2 applications

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The World of Medical Products
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Stem Cells
Advanced Bioprocessing
Interference Genes
Advanced Biomaterials
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The World of Biomaterials

• Broadly Defined
• Categorized by Biocomplexity
• Substrates vs. Scaffolds
• The Basis for Tissue Engineering

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Next Level Biomaterials
Whole Organ Regenerates
Viable, Cellular, Differentiable Materials
Bioactive, Conductive, Remodelable Materials
Biocomplexity
Inert, Inactive, Permanent Materials
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Plastics!
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Substrates Come in Many Forms
Absorbable
Synthetic
Biological
Non-absorbable
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Why next generation biomaterials such as biologic
grafts?
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Why not permanent synthetics?
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Permanent Synthetics

• Are useful in many situations
• But can

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Result in adhesion formation
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Erode into adjacent organs

• Known concern for use of synthetic mesh for
  hiatal hernias
• Can cause fistulas, infections, surface exposure
• Require removal

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Cause chronic pain

• Routinely considered a minor complication in
  inguinal surgery (5-20)
• 11.1 in recent lightweight mesh Lichtenstein
  inguinal hernia study
• Smietanski M et al, Hernia 2009
• Inflammation and mesh interaction has been
  implicated
• Ozkan N et al, J Am Coll Surgery 2008

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Get infected
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A permanent repair does not require a permanent
biomaterial.
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The goal is to balance degradation during
reconstruction
STRENGTH
TIME
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Tissue Engineering Triad
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The New Paradigm for Surgery

• Scaffolding as the implant
• Surgery as the vehicle
• Tissue attachment as the cell source
• Angiogenesis as the prime mechanism
• Complete remodeling as the goal
• Recapitulation of functional tissue as the OUTCOME

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What Is a Remodeling Scaffold?
Host incorporation
Remodeled Tissue
Implanted
Dissolved Support
Breakdown
Biomaterial
Encapsulated Substrate
Strong inflammation
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Why Remodeling

• Safe and effective repair without persistence of
  foreign material
• Capitalize on Mother Natures repair mechanisms
• Not doomed to fail due to dissolution or
  infection
• Scaffolding to guide host response and form
  organized tissue not chaotic scar

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Scar Tissue Is Not Desirable

• It is well-established from the orthopedic and
  body wall literature that scar tissue has only
  70 of the strength of normal, organized tissue.
• Organization and collagen fiber bundle size is
  key.
• Laboratory studies have shown that ECM stimulates
  recapitulation of more normal fiber
  sizes/organization and not scar.

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Tendon Remodeling in the Rabbit Woo, et al., 2006

• Rabbits assigned to no implant or SIS implant
  group
• 6 mm defect in MCL that was either overlayed with
  SIS or left unaugmented
• Evaluated collagen orientation, col V/I ratio,
  ultimate failure stress and strain, and fibril
  diameter at 12 and 26 weeks

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Tendon Remodeling in the Rabbit Woo, et al., 2006
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Tendon Remodeling in the Rabbit Woo, et al., 2006
Normal architecture
SIS Augmented
No Augmentation
The results revealed that in the SIS-treated
group, the collagen fibers were more regularly
aligned as were the cell nuclei. The collagen
fibril diameters were 22.2 larger and the ratio
of collagen type V/I was 28.4 lower than those
for the nontreated group (plt0.05). These
improvements in the morphological characteristics
and biochemical constituents of healing MCLs
following SIS treatment are the likely reasons
for improved mechanical properties.
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Tendon Remodeling in the Rabbit Woo, et al., 2006
Tensile strengths were 50 higher for the
SIS-treated group (3611 MPa) than those for the
nontreated group (249 MPa, plt0.05) at 26 weeks
post-injury.
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What Are Some Scaffolds?

• Some bioresorbable polymers
• Some processed collagen materials
• Natural extracellular matrix (ECM)
• SIS
• UBS
• RCM
• Others

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Source is important

• Small intestinal submucosa (SIS) is isolated from
  the small intestine of pigs
• Consistent U.S. source of same age, weight,
  background, healthy animals
• A naturally strong material

submucosa
mucosa
muscle
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Natural structure of SIS
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Extracellular Matrix

• Ground substance
• The tissue outside the cell
• The cellular nest
• A home for cells
• An attractive environment

Can be harvested and made into a scaffold
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What Is the ECM Made of?

• Primarily collagen
• But in its natural state

• A WHOLE LOT MORE!!

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Natural Extracellular Matrix
Glycosaminoglycans Proteoglycans Glycoproteins Gro
wth Factors
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Stripped Collagen Is Not ECM

• Collagen is the framework, but the other
  components are the biological information
• Grossly altering the structure makes the tissue
  unrecognizable for repopulation
• Crosslinking is a harsh chemical process with
  dire biological consequences

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Mouse implant model

• Rehydrate sample
• Create subcutaneous pocket with blunt dissection
• Implant
• Taking care on placement
• At time point
• Perform microangiography (quantitative or
  qualitative) or collect samples for histology

saline
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Angiogenesis Is Vastly Different
Freeze-dried SIS
Chemically stripped SIS
500X
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Chemical Cross-linking Is Unnatural

• All tissues in the body turn over
• May be imperceptibly slow bone
• May be very quickly mucosa
• Stabilizing a tissue for implant is unnatural
  and can lead to
• Calcification
• Encapsulation
• Disorganized scar formation
• Harnessing turn-over is key!

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Replacement of Tissue Is the Norm

• Hip implants
• Pacemakers
• Dental fillings
• Vascular grafts
• Hernia meshes

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Surgisis can be tailored to fit the application
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Clinical Applications of SIS
Glabellar Lines
Dural Substitute
Tympanoplasty
Corneoplasty
Palate Repair
Facial Reconstruction
Lip Augmentation
Periodontal Graft
Carotid Patch
Tracheoplasty
Pericardial Patch
Staple Line Reinforcement
Lung Perforation Repair

Hemi-nephrectomy Cover
Diaphragmatic Hernia
Gastrocutaneous Fistulas
Paraesophageal Hernia
Gastric Bypass
Inguinal Hernia
Ventral Hernia
Pelvic Organ Prolapse
Anal Fistula
Pubovaginal Sling
Peyronies Repair
Urethral Repair
Vaginal Reconstruction
Diabetic Ulcers
Rectovaginal Fistula
Pressure Ulcers
Venous Ulcers
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Body Wall Reconstruction
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• 55 infants with congenital abdominal defects
  successfully repaired with advanced biomaterials

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Next Level Biomaterials
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Complexity Necessitates Understanding

• Like many tools, the more complex the operation,
  the more likely you need to RTFM.
• Real, long-term benefits for patients can be
  realized if this complexity is properly applied.

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Balancing the 3 Ps
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The Future of T.E. May Be

• Focused on better ways to engineer matrices
• Not all substrates are remodeling scaffolds
• Directed toward more potent ways to attract host
  cells
• Both progenitor and
• Specialized cells
• Driven to better define the proper host OR
  engineering the host to make a better graft
  recipient
• Focusing on the practitioner for acceptance,
  understanding, and proper utilization