Biologics for Sports Injuries Jason L. Dragoo, MD Associate Professor Department of Orthopaedic Surgery Introduction Survey of common conditions Cover only injuries with evidence NOT RTC RTC Pectoralis Epicondylitis No Evidence Some Evidence Good Evidence Hamstring Tendinopath y OA/Cartilage Tendinopath y Types of PRP Inflammatory Anti-inflammatory IL-1β IL-6 IFN-γ TNF-α IL-4 IL-10 PPP + + LP-PRP + + + LR-PRP + + + + + RBC + LR-PRP (WBC rich) = inflammatory LP-PRP (WBC poor) = anti-inflammatory 1
Types of Stem Cells Bone Marrow Derived (BMSC) Harvested via: Iliac crest (low numbers) Needs concentration (BMAC) Adipose Derived (ADSC) Harvested via: Fat pad (arthroscopic) Abdomen/buttock PRP: Lateral Epicondylitis 29 Studies PRP vs Corticosteroids 6 vs 3 PRP vs Local Anesthetic 3 vs 0 PRP vs Laser Therapy 1 vs 1 PRP vs Whole Blood 4 Similar! Best evidence LR-PRP (WBC) or Whole Blood Muscle Injury: Hamstring/Pectoralis Injury Differentiation: muscle fiber production Proliferation: number of myoblasts/fibroblasts (leads to scar tissue) 2
PRP doesn t work for Muscle Regeneration PRP shown to lead to proliferation Many reports that patients are worse with PRP: Pain/myositis ossificans Animal Trial Muscle regeneration (PPP) vs fibrosis (PRP) PPP PRP 3
Muscle Regeneration PPP used 2 weeks after injury Standard pain-free rehab Returned to play at 6 wks Injury No loss of strength or ROM 3 month follow up PRP: Patellar Tendinopathy 19 Studies One vs Multiple Injections(x2) PRP vs Shockwave Therapy PRP vs Dry Needling After ACLR - BTB Best evidence: LR-PRP (WBC) PRP: Symptoms of Osteoarthritis If OA has an inflammatory component PRP= Anti-inflammatory effect 4
PRP: OA symptoms Level I studies PRP better than HA LP-PRP 5 (n=570) LR-PRP 1 (n=160) Use of LP-PRP (non-wbc) recommended AJSM, 2015 LP-PRP significantly better than than HA LR-PRP no difference compared to HA BMAC: OA Symptoms Shapiro et al, AJSM 2017 (OA RCT) Similar pain relief to saline injections Chahla et al, OJSM 2016 (Review) Madry et al, Stem Cells International 2017 Low Quality Studies Mechanisms Unknown 5
ADSCs Open harvest Cultured 3 weeks + PRP n=18 patients ADSC Injection o Ž T šœgp ŒŠ agj ˆ š ŒGY Results: WOMAC: 49.9 30.3 Lysholm: 40.1 73.4 Pre injection Post injection @ 6mo Human Double Blind RCT: OA Stem Cells + Arthroscopy Standard arthroscopy Arthroscopically harvested ADSCs Processing in OR Removal of Ca +2 cartilage Injection after closure Arthroscopy alone Meniscectomy, LB, synovectomy 4 days TDWB/full ROM Saline injection Outcome measures: KOOS, VAS, MRIs- T1ρ and T2 Map @ 6mo, 1, 2 yr follow-up OA Trial Early Results Pre-op 1 year post-op 6
Human RCT: Chondral Defect Stem Cell Treatment Arthroscopically harvested ADSCs Cell concentration Autologous fibrin glue FDA approved matrix No marrow stimulation Microdrilling plus Std treatment FDA approved matrix 8 weeks TDWB Stratified for lesion size Outcome measures: KOOS, VAS, MRIs- T1ρ and T2 Map @ 6mo, 1, 2 yr follow-up Cartilage Defect Study Patient 1 Patient 2 Augmentation of Meniscal Repairs? Intrinsic healing rate of meniscus repairs is poor Average failure rate of 23.1% at 5 years post-repair (Nepple, 2012) Open: 16-29% (Sommerlath, 1989; Sommerlath, 1991; Rockborn, 2000) Outside-in: 23.9% (Majewski, 2006) Inside-out: 0-29% (Eggli, 1995; Johnson, 1999; Steenbrugge, 2004; Logan, 2009) All inside: 4-28.6% (Lee, 2005; Logan, 2009) 7
ACLR + meniscal repair improved healing vs. isolated meniscal repair Biologic Augmentation Meniscal Tears Reasonable human trial evidence Animal only trials/ minimal evidence Cell Therapy ACL Recon Biologics Rasping Little to NO evidence PRP Trephination Fibrin Clot ACL Reconstruction Murray et al, OJSM 2016 Figueroa et al, 2015 Andriolo et al, 2015 Moraes et al, 2014 Arthroscopy Biomed Res Int Cochrane Library Enhance Graft to Bone Healing: unlikely Accelerate Graft Remodeling: maybe Improve Clinical Outcomes: no evidence 8
PRP: Achilles Tendinopathy 24 Studies PRP vs Saline (x2) PRP vs Rehab Repair + PRP No Significant difference Evidence for use of PRP PubMed article search: 9,212 Lateral Epicondylitis Patellar Tendinopathy OA symptoms Inflammation Level I Evidence Yes Yes Yes Yes Little Evidence for PRP RTC Repair Achilles Tendinopathy Acute Injury Intra-operative use Cartilage regeneration Muscle regeneration Bone regeneration Meniscal repair Improved love life Baldness 9
4 Which PRP system should I use? Choose flexible system Can produce multiple formulations Low/high WBCs, RBCs, PLT Amniotic Fluid and Cells Not much data! FDA tightened language for use Allograft biology 10
Slide 28 4 Jason Dragoo, 5/1/2014