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BioCartilage
                Alan M. Hirahara, M.D., FRCS(C)
       Board Certified in Orthopaedic Surgery & Orthopaedic Sports Medicine
                    Specializing in arthroscopic shoulder surgery




     Medical Director               Team Physician              Consultant
Sacramento State Athletics       Sacramento River Cats          Oakland A’s
                                      MiLB - AAA
Micronized Cartilage ECM
•   Potential augment for Microfracture
     –   Provides cartilage ECM scaffold
     –   Allows for BM MSC attachment and growth
     –   Stem Cells exposed to ECM will differentiate based on factors present within the matrix
     –   Glycoproteins/Proteoglycans
     –   Simple / inexpensive

•   Cheng et al (Tissue Engineering 2009)
     –   Adult stem cells seeded onto the lyophilized cartilage scaffold
     –   Chondrogenesis of ASCs evident by PCR & immunohistochemical examination
     –   Resembled native articular cartilage




                                                                                                   Cheng N et al. Tissue Engineering 2009.
BioCartilage ECM
           Micronized Cartilage Matrix
•   Potential augment for microfracture?
     –    Allograft cartilage ECM scaffold
     –    Allows for BM MSC attachment and growth
     –    Simplistic / inexpensive


•   In vitro evidence supporting this theory:
     –    Adipose stem cells seeded onto lyophilized cartilage
          scaffold
     –    Chondrogenesis of ASCs evident by PCR and
          immunohistochemistry
             •   Abundant production of type II collagen
     –    Cellular morphology resembled native articular cartilage


     –    Cheng N et al. Chondrogenic differentiation of adipose-
          derived adult stem cells by a porous scaffold derived from
          native articular cartilage extracellular matrix. Tissue
          Engineering 2009; 15(2): 231-41.
BioCartilage ECM
            Micronized Cartilage Matrix
•   In vivo supportive evidence:
      –    Same scaffolding material used within the previous mentioned
           in vitro study
      –    Medial femoral condyle defects created within a rabbit model
               •    Control group = microfracture performed
               •    Treatment group = MFx plus lyophilized cartilage fagments
                    formed into a scaffold                                       Control Group
      –    Treatment group had persistent upregulation of cartilage
           phenotypic markers: Type II Collagen and Aggrecan


      –    Chadha N et al. Porous Cartilage-Derived Matrix Scaffolds for
           Repair of Articular Cartilage Defects. ORS 2012; Poster No. 0735.


                                                                                Treatment Group
Literature
• Re: Tendon-to-bone healing. “Increase in the strength of the
  interface … [is] proportional to the amount of osseous ingrowth.”
       • Rodeo, Arnoczky et al., JBJS(A) 1993;75: 1795–1803



• Improving the osteoconductive/inductive environment
  improves tendon-bone healing
       • Shen H, et al. Int Orthop. 2010;34;(6)917-24.
       • Hioki S, et al. Am J Sports Med. 2012;40;(8)1772-80.
       • Kadonishi Y, et al. JBJS(B). 2012;94;(2)205-9.
BioCartilage ECM
         Micronized Cartilage Matrix
•   In vivo supportive evidence:
     –   Baboon osteochondral defects filled with
         micronized cartilage particulate
           •   15 mm diameter, 10 mm depth

     –   By 9 weeks had gross appearance of
         hyaline like cartilage
     –   Histo: Newly formed cartilage cells,
         normal appearing proteoglycan content
     –   Control group remained open or
         contained uneven patches of tissue


     –   Malinin T et al. Induction of regeneration
         of articular cartilage defects by freeze
         dried particulate cartilage allografts. ICRS
         2009 Meeting; poster presentation.
                                                        12 weeks
BioCartilage ECM
       Micronized Cartilage Matrix
• Future In vivo support:
    – Full thickness cartilage defects
    – Microfracture vs. BioCartilage
    – Cole, Fortier, Cook
• Future clinical support:
    – Post market release study for
       femoral condyle lesions
    – Post market release study for
       talar lesions
DeNovo NT (Zimmer)
          •   DeNovo NT
               –   Juvenile, allograft cartilage      minced
                   into 1 mm cubes
               –   Priced around $4,500
                     •   BioCartilage = $750

               –   Shelf life less than 1 month
                     •   BioCartilage = 4 years

               –   Arthroscopic application is difficult
                     •   BioCartilage has paste like consistency
                         when mixed with autologous blood ,
                         allowing for delivery through a needle
Microfracture “Plus”
                                        Sheep Pre-Clinical
• BST CarGel                                 Model

   – Piramal Healthcare
   – Chitosan based scaffold
     mixed with blood
       • Shrimp exoskeleton    Microfractur              Chitosan +
                                    e                      Blood
   – Received CE mark
     approval April 2012
   – Conducting randomized
     pivotal trial in Canada
                                Gross – 6                    Histo – 6
                                 month                        month
Relative Costs
• ACI (Genzyme)                        • BioCartilage (Arthrex)
   – $10,000                               – $750
        • Cost for cultured cells          – Morselized, dehydrated cartilage
   – Must add costs of two surgeries       – Arthroscopic
   – Open Procedure

• DoNovo NT (Zimmer)
   – $4,500 – Live cells
   – Juvenile, allograft cartilage
      minced into 1 mm cubes
   – Open procedure
BioCartilage: The Shoulder
BioCartilage: Trochlea (Knee)
BioCartilage: LFC (Knee)
Looks easy?
Deleted Scenes
How Should We Do It?
Open                Arthroscopy

• Easy              • Very challenging

• Inexpensive       • Clean margins

• Quick                – Curette / Burr

                    • Instrumentation
                       – Cannulas

                       – Double lumen applicator for
                          fibrin covering
Mixing and Delivery System
BioCartilage Mixing and
   Delivery System
                   3
 1        2




                   4




 5            6
Tips
•   Overlay fibrin glue (Evicel) to adhere to native
    cartilage
     –   Use a double lumen syringe system
     –   Don’t overuse fibrin, add slowly & carefully
     –   Tisseel has own double lumen syringe avail.


•   Use cannula
     –   Easier, more reliable instrument insertion
     –   Not to disturb fibrin clot or sculpted biocartilage


•   Make good vertical margins
     –   Prefer curette with microfracture
     –   BEWARE making divots with burrs
Tips
• Suction out fluid
   – Keep it DRY!!!



• Do not overhydrate BioCartilage with ACP
   – 1.0 cc
   – Want a “tacky paste”
My Experience
       Shoulders – 6                              Knees – 4

• All humeral head lesions           • 2 Trochlear lesions

                                     • 1 LFC lesion

                                     • 1 MFC lesion




               All procedures performed arthroscopically
CASE PRESENTATION
Reverse Hill-Sachs Lesion
BioCartilage
BioCartilage
Thank You!
HiraharaMD.com

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BioCartilage Update 2013

  • 1. BioCartilage Alan M. Hirahara, M.D., FRCS(C) Board Certified in Orthopaedic Surgery & Orthopaedic Sports Medicine Specializing in arthroscopic shoulder surgery Medical Director Team Physician Consultant Sacramento State Athletics Sacramento River Cats Oakland A’s MiLB - AAA
  • 2. Micronized Cartilage ECM • Potential augment for Microfracture – Provides cartilage ECM scaffold – Allows for BM MSC attachment and growth – Stem Cells exposed to ECM will differentiate based on factors present within the matrix – Glycoproteins/Proteoglycans – Simple / inexpensive • Cheng et al (Tissue Engineering 2009) – Adult stem cells seeded onto the lyophilized cartilage scaffold – Chondrogenesis of ASCs evident by PCR & immunohistochemical examination – Resembled native articular cartilage Cheng N et al. Tissue Engineering 2009.
  • 3. BioCartilage ECM Micronized Cartilage Matrix • Potential augment for microfracture? – Allograft cartilage ECM scaffold – Allows for BM MSC attachment and growth – Simplistic / inexpensive • In vitro evidence supporting this theory: – Adipose stem cells seeded onto lyophilized cartilage scaffold – Chondrogenesis of ASCs evident by PCR and immunohistochemistry • Abundant production of type II collagen – Cellular morphology resembled native articular cartilage – Cheng N et al. Chondrogenic differentiation of adipose- derived adult stem cells by a porous scaffold derived from native articular cartilage extracellular matrix. Tissue Engineering 2009; 15(2): 231-41.
  • 4. BioCartilage ECM Micronized Cartilage Matrix • In vivo supportive evidence: – Same scaffolding material used within the previous mentioned in vitro study – Medial femoral condyle defects created within a rabbit model • Control group = microfracture performed • Treatment group = MFx plus lyophilized cartilage fagments formed into a scaffold Control Group – Treatment group had persistent upregulation of cartilage phenotypic markers: Type II Collagen and Aggrecan – Chadha N et al. Porous Cartilage-Derived Matrix Scaffolds for Repair of Articular Cartilage Defects. ORS 2012; Poster No. 0735. Treatment Group
  • 5. Literature • Re: Tendon-to-bone healing. “Increase in the strength of the interface … [is] proportional to the amount of osseous ingrowth.” • Rodeo, Arnoczky et al., JBJS(A) 1993;75: 1795–1803 • Improving the osteoconductive/inductive environment improves tendon-bone healing • Shen H, et al. Int Orthop. 2010;34;(6)917-24. • Hioki S, et al. Am J Sports Med. 2012;40;(8)1772-80. • Kadonishi Y, et al. JBJS(B). 2012;94;(2)205-9.
  • 6. BioCartilage ECM Micronized Cartilage Matrix • In vivo supportive evidence: – Baboon osteochondral defects filled with micronized cartilage particulate • 15 mm diameter, 10 mm depth – By 9 weeks had gross appearance of hyaline like cartilage – Histo: Newly formed cartilage cells, normal appearing proteoglycan content – Control group remained open or contained uneven patches of tissue – Malinin T et al. Induction of regeneration of articular cartilage defects by freeze dried particulate cartilage allografts. ICRS 2009 Meeting; poster presentation. 12 weeks
  • 7. BioCartilage ECM Micronized Cartilage Matrix • Future In vivo support: – Full thickness cartilage defects – Microfracture vs. BioCartilage – Cole, Fortier, Cook • Future clinical support: – Post market release study for femoral condyle lesions – Post market release study for talar lesions
  • 8. DeNovo NT (Zimmer) • DeNovo NT – Juvenile, allograft cartilage minced into 1 mm cubes – Priced around $4,500 • BioCartilage = $750 – Shelf life less than 1 month • BioCartilage = 4 years – Arthroscopic application is difficult • BioCartilage has paste like consistency when mixed with autologous blood , allowing for delivery through a needle
  • 9. Microfracture “Plus” Sheep Pre-Clinical • BST CarGel Model – Piramal Healthcare – Chitosan based scaffold mixed with blood • Shrimp exoskeleton Microfractur Chitosan + e Blood – Received CE mark approval April 2012 – Conducting randomized pivotal trial in Canada Gross – 6 Histo – 6 month month
  • 10. Relative Costs • ACI (Genzyme) • BioCartilage (Arthrex) – $10,000 – $750 • Cost for cultured cells – Morselized, dehydrated cartilage – Must add costs of two surgeries – Arthroscopic – Open Procedure • DoNovo NT (Zimmer) – $4,500 – Live cells – Juvenile, allograft cartilage minced into 1 mm cubes – Open procedure
  • 16. How Should We Do It? Open Arthroscopy • Easy • Very challenging • Inexpensive • Clean margins • Quick – Curette / Burr • Instrumentation – Cannulas – Double lumen applicator for fibrin covering
  • 18. BioCartilage Mixing and Delivery System 3 1 2 4 5 6
  • 19. Tips • Overlay fibrin glue (Evicel) to adhere to native cartilage – Use a double lumen syringe system – Don’t overuse fibrin, add slowly & carefully – Tisseel has own double lumen syringe avail. • Use cannula – Easier, more reliable instrument insertion – Not to disturb fibrin clot or sculpted biocartilage • Make good vertical margins – Prefer curette with microfracture – BEWARE making divots with burrs
  • 20. Tips • Suction out fluid – Keep it DRY!!! • Do not overhydrate BioCartilage with ACP – 1.0 cc – Want a “tacky paste”
  • 21. My Experience Shoulders – 6 Knees – 4 • All humeral head lesions • 2 Trochlear lesions • 1 LFC lesion • 1 MFC lesion All procedures performed arthroscopically