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 ConsultantSacramento 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 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