Evolving Technique Update: How Orthobiologics are Transforming Hip - PowerPoint PPT Presentation

Evolving Technique Update: How Orthobiologics are Transforming Hip Preservation Misty Suri M.D. Medical Director, Head Team Physician New Orleans Pelicans (2007-2017) Team Physician New Orleans Saints Team Physician University of New Orleans Consultant: LSU Athletics Ochsner Sports Medicine Institute Art Villarreal M.D. (fellow)

Orthobiologics • Bone morphogenic proteins • Platelet rich plasma • Hyaluronic acid • Cell therapy

BMP • Member of TGF- β superfamily • Osteogenic activities & promote cartilage formation

• 39 hips Ficat & Arlet stage II or III • trapdoor technique for removal of necrotic bone & placement of autologous cancellous bone graft & BMP-7 • clinical success in 67% – no THA at mean 36 mo f/u

• 72 hips (42 pts) • followed 5-8 years (mean 6.1 years) • Group 1 – ICBG + Novobone (artificial bone) & rhBMP-2 • Group 2 – ICBG + Novobone • survival rate – group 1: 82% – group 2: 72%

Platelet Rich Plasma

• Study group - 91 pts receiving intraarticular PRP • Control group - 180 pts receiving intraarticular 0.25% bupivacaine • No difference in pain at 3 months • PRP group with higher pain at 2 years – 3.4 vs 2.5 p=.005 • PRP group with lower mHHS at 2 years – 79 vs 83 p=.049

• 111 pts receiving weekly IA injection x 3 wks • 3 groups – PRP (44 pts) – PRP+HA (31 pts) – HA (36 pts) • 6 mo VAS scores (mm) : – PRP 21 p=.007 – PRP+HA 35 – HA 44

Hyaluronic Acid

• 85 pts; 2.5 ml HA group- 42, 2.5 ml saline-43 – single 2.5 ml injection • Main outcome VAS on 100mm scale • At 3 months no difference in VAS – -7.8 +/- 24.9mm with HA vs. – -9.1 +/- 27.4 mm saline p=.98

• Meta-analysis of 23 studies – studies w/ highly variable end points, control groups & f/u – mean decrease in VAS across all studies: 1.97 – in randomized studies decrease was: 0.27 • ? minimal clinical relevance

Cell Therapy

• 38 pts (48 hips) – hip arthroscopy & IA BM-MSC infusion • BM-MSC from iliac crest, expanded & given as series of 3 injections from 4-6 wks postop • Median f/u 30 months – VAS 4 to 2 p< 0.01 – mHHS 63 to 72 p< 0.01 – 2 failures (THA)

• 16 hips in 14 pts with ICRS 3 & 4 – Stem cells from peripheral blood – Microfracture > scaffold placed > stem cells injected into scaffold – Mean f/u 16 months – Hip Outcome Score 67 to 95 p< 0.05

• 80 pts w/ ICRS 2-4 – 40 w/ BM-MSC & biodegradable scaffold – 40 microfracture alone – mean f/u 28 months – mHHS, patient satisfaction, Non-arthritic hip score – MSC group • mHHS 63 to 87, patient satisfaction 5.2 to 9, NAHS 61 to 82 – control • mHHS 62 to 76, patient satisfaction 5.5 to 8.4, NAHS 62 to 76

inner outer

Amniotic membranes • Anti scarring/wound healing • Reduce inflammation • Anti microbial • Nonimmunogenic

Amniotic membranes • Anti scarring/wound healing – down regulation of TGF- β reducing activation of fibroblasts – EGF, KGF & HGF – decreased adhesions • flexor tendon repair, nerve wrap/conduit (human) • rat model of peritoneal adhesions • Riboh, JC. Et al. Am J Sports Med. 2016 Sep;44(9):2425-34 • J Kuckelman, J Smith, K Kniery, J Kay, S Lyon, Z Hoffer, S Steele, V Sohn Diseases of the Colon & Rectum 60 (6), E98-E98 • Mamede AC. Et al. Cell Tissue Res. 2012;349(2):447-458. • Koizumi NJ. Et al. Curr Eye Res. 2000;20(3):173-177. • Fairbairn NG, Randolph MA, Redmond RW. J Plast Reconstr Aesthet Surg. 2014;67(5):662-675. • Niknejad, H. et al. Eur Cell Mater. 2008 Apr 29;15:88-99.

Amniotic membranes • Reduce inflammation – suppression of IL-1 α , IL-1 β and MMPs • Khouw et al . Biomaterials 20 :815-1822. • Tseng et al . J Cell Physiol 179 : 325-335. • Lee et al . Curr Eye Res 20 : 325-334. • Solomon et al . Br J Ophthalmol 85 : 444-449. • Hao et al . Cornea 19 : 348-352. • Kim et al . Exp Eye Res 70 : 329-337. • Higa et al . Cornea 24 :206-212.

Amniotic membranes • Anti microbial – AM cells produce antimicrobial molecules: • bactricidin • β -lysin, transferrin • 7S immunoglobulin • β 3 defensin • cystatin 3 • Krisanaprakornkit et al . Infect Immun 66 : 4222-4228. • Harder et al . Am J Respir Cell Mol Biol 22 : 714-721. • Galask RP, Snyder IS. Am J Obstet Gynecol. 1970;106(1):59-65. • Koizumi NJ. Et al. Curr Eye Res. 2000;20(3):173-177. • Malhotra C, Jain AK. World J Transplant. 2014;4(2):111-121. • Sangwan VS, Basu S. Br J Ophthalmol. 2011;95(1):1-2.

Amniotic membranes • Nonimmunogenic – lack of HLA-: A, B, & DR – HLA-G induces immune tolerance through inhibition of NK cells & macrophages – reduce activation of T-cells through regulation of multiple cytokines such as IL-2, -4, -7, -15 and IFN- γ • Malhotra C, Jain AK. World J Transplant. 2014;4(2):111-121. • Insausti CL, et al. Stem Cells Cloning. 2014;7:53-63. • Banas R, et al. Cell Transplant. 2014;23(9):1111-1125. • Kang JW, et al. J Vet Sci. 2012;13(1):23-31. • Magatti M, et al. Cell Transplant. 2009;18(8):899-914. • Higa et al . Cornea 24 :206-212. • Hori et al . Cornea 25 : S53-S58. • Sargent, IL. Exp Clin Immunogenet 10 : 85-102. • Szekeres-Bartho, J. Int Rev Immunol 21 :471-495.

Amniotic membranes • Nonimmunogenic – AM-derived stem cells effect on the immune system due to ability to prevent monocyte differentiation into dendritic cells • key cell type for antigen presentation • Malhotra C, Jain AK. World J Transplant. 2014;4(2):111-121. • Insausti CL, et al. Stem Cells Cloning. 2014;7:53-63. • Banas R, et al. Cell Transplant. 2014;23(9):1111-1125. • Kang JW, et al. J Vet Sci. 2012;13(1):23-31. • Magatti M, et al. Cell Transplant. 2009;18(8):899-914. • Higa et al . Cornea 24 :206-212. • Hori et al . Cornea 25 : S53-S58. • Sargent, IL. Exp Clin Immunogenet 10 : 85-102. • Szekeres-Bartho, J. Int Rev Immunol 21 :471-495.

Amniotic membranes • ?chondrogenic – cell culture studies • AM-derived pluripotent cells can be directed to chondrogenic line via BMP-2, BMP-7, or chondrogenic medium • also can serve as scaffold for – bone marrrow derived MSC adhesion – chondrogenic differentiation – chondrocyte adhesion & proliferation • Malhotra C, Jain AK. World J Transplant. 2014;4(2):111-121. • Insausti CL, et al. Stem Cells Cloning. 2014;7:53-63. • Banas R, et al. Cell Transplant. 2014;23(9):1111-1125. • Kang JW, et al. J Vet Sci. 2012;13(1):23-31. • Magatti M, et al. Cell Transplant. 2009;18(8):899-914. • Higa et al . Cornea 24 :206-212. • Hori et al . Cornea 25 : S53-S58. • Sargent, IL. Exp Clin Immunogenet 10 : 85-102. • Szekeres-Bartho, J. Int Rev Immunol 21 :471-495.