Conclusion The Future of ACL Injury

Size: px
Start display at page:

Download "Conclusion The Future of ACL Injury"

Transcription

1 Conclusion The Future of ACL Injury Bones had a job I totally envy. He was the doctor on Star Trek, and whenever someone was hurt, he came in with his tricorder, waved it over the patient and it told him the diagnosis. Even better, he could push a second button on the device, wave it over the patient again, and the problem would be fixed. No wonder a $10 million prize has recently been offered to anyone who can develop a working tricorder. Unfortunately, we do not have that technology yet. While we have ways to accurately diagnose ACL tears via physical examinations and magnetic resonance imaging, we still need to perform extensive surgery to replace the torn ligament. When I think about the future of ACL surgery, I think about the tricorder solution can we develop a noninvasive way to treat ACL injuries? Steps along that path include making surgery less invasive. Our profession has already made great strides in this direction. The advent of arthroscopic surgery where much of the operation can now be performed through small incisions using a camera to see inside the joint has been a major advance. The use of smaller incisions to harvest both hamstring and patellar tendon grafts as well as the invention of fixation devices that can be used to secure the graft without direct visualization have also made our surgery easier on patients. Enhancing primary (suture) repair of the ACL using a biologic scaffold is the next logical step. This technique avoids the need for graft harvest, thus maintaining the normal anatomy of the extensor mechanisms of the knee as well as the hamstring musculature (without the risks of infection or elevated failure rates associated with allografts). The specifics of this technique will undoubtedly improve as we see how patients respond to this new therapy, and we learn more about the biology of the joint and its response to this treatment. Improved understanding of the individual types of blood cells, their role in the wound healing process, identification of the complex array of interacting growth factors in the injured joint, and a better understanding of all the pathways that stimulate matrix production and organization will M.M. Murray et al. (eds.), The ACL Handbook: Knee Biology, Mechanics, and Treatment, DOI / , Springer Science+Business Media New York

2 310 Conclusion all help to improve the repair process for the ACL and other commonly injured intra-articular structures including the posterior cruciate ligament, menisci, and the shoulder rotator cuff tendon. It is my hope that one day, we will be able to stimulate repair of the ACL with techniques that are even less invasive and more effective at stimulating the regeneration of this ligament. Perhaps someday, an ACL injury will not feel like a death sentence for an athlete. When Emily tears her ACL in the future, she will be carried off the field and may only need a simple injection into her knee, possibly guided by ultrasound or another imaging modality, to assure proper placement of a scaffold and the introduction of the right biologic stimuli. A tricorder would be even better. Perhaps the final frontier will be in the prevention of these injuries. I expect we will see advances in all of these areas in the near future, and it will be an exciting time as we boldly go where no one has gone before.

3 A Achilles tendon allografts fresh/frozen, 148 with and without BMSCs, 208 tissue engineering, 170 ACL healing. See also Wound healing age and skeletal maturity effect bio-enhanced suture repair, 301, 302 cellular level mechanisms, 305, 306 histologic sections, 303, 304 ligament appearance, 302, 303 photomicrographs, ACL insertion site, 304, 305 PRP, in vivo model, complete ACL tear absorbable vs. nonabsorbable sutures, 235 ECM-based scaffold and platelet, platelet carrier, stimulation of, platelet deliver, platelet-rich plasma use, platelet vs. carrier alone, selection and validation, surgical technique improvement, suture technique, wound (see Wound healing) ACL prevention program, ACL reconstruction. See Anterior cruciate ligament reconstruction (ACLR) ACL repair safety collagen-based biomaterials, 265 ECM scaffold complications, 269, 271 definition, 266 immunologic response, 266 parameters determination cytokines, 267 flexion vs. extension, 266 leukocytosis, 267 MRI measurement, 266, 267 physical properties, 266 porcine model, intra-articular collagen safety platelet concentration, 268 PRP vs. non-prp group, 270 qualitative histological evaluation, 269 SPONGE/CPC-GEL, 269 SPONGE/ECM, 268 synovial thickness, MRI, 270 ACL response, injury cell collagen production after injury, 95 cell migration after injury ACL explants, 92, 93 fibroblasts, 93 two-dimensional cultures, 94 cell proliferation after injury, histologic phases, 97 inflammatory phase, 98 epiligamentous regeneration phase, 97 proliferative phase, 99 remodeling phase, 99 vascularity changes, ACL tears. See Partial ACL tears; Pediatric ACL tears M.M. Murray et al. (eds.), The ACL Handbook: Knee Biology, Mechanics, and Treatment, DOI / , Springer Science+Business Media New York

4 312 ACL treatment children extraosseous stabilization techniques, growth plates, nonsurgical treatment history, physeal-sparring ACL reconstruction, physis closure, 44 prevention, skeletal growth, 42 surgical treatment, 47 tanner I and II, transphyseal ACL reconstruction, 42 43, treatment, current gold standard method, history ACL reconstruction, Claudius Galen contribution, primary repair, Segond fracture, 20 synthetic replacement, Age and skeletal maturity effect, ACL healing. See also Pediatric ACL tears bio-enhanced suture repair, 301, 302 cellular level mechanisms, 305, 306 histologic sections, 303, 304 ligament appearance, 302, 303 photomicrographs, ACL insertion site, 304, 305 PRP, Allografts Achilles tendon fresh/frozen, 148 with and without BMSCs, 208 ACL reconstruction, 35 vs. autograft, biological scaffolds, 205 Anterior cruciate ligament (ACL) biology cell type endoligament, 70 fibroblast, 68 in animal study, 69 mechanoreceptors, 70 microscopic appearance/histology, nuclear shapes, 68 shapes, 69 growth and development, physiologic function anatomy and location, 63, 64 function, 65 plant and pivot motion, 63, 64 role, 63 stretchability, 65, 66 waviness/crimp, photomicrograph, 65 structure components, 68 type I collagen, Anterior cruciate ligament reconstruction (ACLR). See also ACL response, injury ACL ruptures prevention, 37 allograft, 35 allograft vs. autograft, complications, endoscopic/two incisions, hamstring/patellar tendon, autograft use, indications, 30 isolate ACL tear, LOE I and LOE II, 34 medial collateral ligament, metal/bioabsorbable screws, 36 rehabilitation, 36 single/double bundle, 34 Anteroposterior laxity testing, 191 Autografts vs. allograft, biological scaffolds advantage, 204 incomplete ligamentization, 205 ligamentization process, 204 use, hamstring/patellar tendon, B Bench to bedside approach. See Translational medicine Bio-enhanced ACL reconstruction. See Healing, ACL graft Biological scaffolds, ACL allografts, 205 autografts, cell seeding, collagen scaffolds/xenografts, collagen scaffold vs. PRP, growth factors, 208 platelet-rich plasma (PRP), synthetic materials, tissue engineering, 203 B lymphocytes, ligament healing, 260 Bone marrow stromal cells (BMSCs),

5 313 C Cell seeding anterior cruciate ligament fibroblasts, 207 bone marrow stromal cells, Collagen ACL biology, 66 biological scaffolds clinical applications, 206 limitation, 207 vs. PRP, cell, 95 description, 67 formation, impaired healing, ultrastructure, 67 Complete ACL tear. See ACL healing Crimp biology, tissue engineering, 169 Cytokines, 267. See also Platelets E Endoligament, 70, 130 Enzyme-linked immunosorbent assay (ELISA) ACL tissue engineering, 184 in vitro models, 128 Epidemiology, ACL injury age-specific risks, 9 cost, data, 4 5 description, 3 4 female athletes, 6 7 frequency, ACL tears, 5 prevention, reoccurrence, ACL tear, sports-specific risks, 7 9 surgery rate, 12 vulnerable persons, 5 Epiligament, 103 Erythrocytes. See Red blood cells (RBCs) Extracellular matrix (ECM) scaffold bioenhanced repair safety complications, 269, 271 definition, 266 deposition, 85 and platelets, 235 (see also Platelets) F Fibroblast growth factor (FGF-2), Fibroblasts, Flexcell bioreactor, 133 G Gait analysis techniques, 192 Granulocytes, wound healing basophils, 81 eosinophils, 81 neutrophils apoptotic process, 81 migration, 80 Growth factors, collagen synthesis, 208, 209 H Healing, ACL graft. See also Wound healing biology of, 286 blood clot constituents, 287 cell-enhanced ACL reconstruction, growth factor exogenous application, 288 preclinical studies, 289 released platelets, 288 VEGF-treated grafts, 289 intra-articular, 287 platelets, 293 ACL-reconstructed group, activation, 287 collagen-platelet hydrogel, 291 CPC, 290, 291 future work, 295 uses, 289 reconstruction procedures, 287 I Impaired healing, joint issues ACL vs. MCL head-to-head test, healing, 102 cellular response characterization, 102 collagen formation, epiligament and endoligament response, 103 extra-articular wound healing, 106 intra-articular wound healing, revascularization response, 103 scaffold formation, Inflammatory phase, ACL injury response, 98 epiligamentous regeneration phase, 97 proliferative phase, 99 remodeling phase, 99 Insulin-like growth factor (IGF), 241 Intra-articular ligament. See Anterior cruciate ligament (ACL) biology

6 314 In vitro models, ACL injury ACL vs. MCL cell behavior, 129 advantages, biologic mechanism, 125 biosynthesis, 128 cell culture medium, 124 complex wound models bioreactor designs, flexcell bioreactor, 133 ligament bioreactor, 134 Wolff s law, history, 123 migration, outcome assessment biochemistry and molecular biology, histology, penicillin, mold juice, 123 proliferation cell-staining method, flow cytometry principle, 127 MTT assay, 128 spectromorphometric analysis, wound models cells alone, 130 cells and biomaterials, high-density cell culture, 131, 132 scratch test, 130 In vivo models, ACL injury canine (dog) biologic augmentation, 151 biomechanical data, 150 caprine (goat) ACL graft tensioning, 156 AP laxity, 157 biomechanical data, 154 collagen scaffold grafts, patellar tendon graft, 157 primary suture repair, 157 complete ACL tear absorbable vs. nonabsorbable sutures, 235 ECM-based scaffold and platelet, platelet carrier, healing stimulation, platelet deliver, platelet-rich plasma use, healing, platelet vs. carrier alone, selection and validation, surgical technique improvement, suture technique, human ACLs vs. large animal models, interspecies differences gross anatomy vs. knee biomechanics, 141, 142 range of motion, goniometer, 143 statistical analysis, 143 tensile strength, 141 knee stabilization, 139 ovine (sheep) ACL grafts, biologic enhancements, 155 biomechanical data, effects of choosing grafts, 155 fixation techniques, 151 primary suture repair, PRP preparation, 151 porcine (pig) bio-enhanced ACL repair, 160 biomechanical data, 158 fixation technique, 159 in situ forces, 159 rabbit biomechanical data, 147 BMP2, 148 semitendinosus tendon grafts, 146 synthetic grafts, 148 rodents advantages, 144 biomechanical data, 145 injection of MSCs, 144 macrophages depletion, 144 semitendinosus tendon, 144 weaknesses of, 140 J Joint function anteroposterior laxity testing, 191 gait analysis techniques, 192 passive knee laxity measurements, 190 L Lachman test, 194 Leukocyte-adhesion deficiency-1 (LAD-1), 254 Leukocytes. See White blood cells (WBCs) Ligament bioreactor, 134

7 315 Ligament healing. See ACL healing erythrocytes, leukocytes, 252 lymphocytes B cells, 260 T lymphocytes, macrophages, material properties, 188 multiple cell types, 250 neutrophils, structural properties, and tendons, tissue engineering (see Tissue engineering) tensile failure testing, 187 viscoelastic properties, 189 Lymphocytes ligament healing B cells, 260 T lymphocytes, wound healing, M Macrophages ligament healing alternatively activated (M2), 257 classically activated (M1), gene expression and function, 256 MCL transection vs. ACL reconstruction, 258 monocytes and, 255 primary ACL repair, 258 regulatory, 82 wound healing, 82 Mechanoreceptors, 70, 276 Medial collateral ligament (MCL) ACL healing, head-to-head test, healing, 102 ligament healing, 257 partial ACL tears, 217 Megakaryocyte, 77, 239 Monocyte, wound healing, 83 N Neutrophils, ligament healing acute inflammatory response, apoptotic process, 254 blood components role, 253 LAD-1, 254 platelet-rich plasma, robust inflammation, 253 P Partial ACL tears central cut, 216 individual growth factors collagen-gag sponge, 218 FGF-2, macroscopic observation, medial collateral ligament, 217 wound healing process, 218 model development biomechanical strength, ACL healing, collagen-platelet composites use, functional histologic response, ligament strength restoration, 222 patellar ligament wounds, 221 wound sites comparison, 220 scaffold formation, 216 Passive knee laxity, 190 Patellar ligament wounds, 221 Pediatric ACL tears. See also ACL treatment growth plates injury, risk, damage of, 43 structure, knee, 42 nonsurgical treatment history, physeal-sparring ACL reconstruction extraosseous stabilization techniques, transosseous, physis closure, 44 prevention, skeletal growth, 42 surgical treatment, 47 tanner I and II, transphyseal ACL reconstruction, 42 43, treatment, Pivot shift test, 194 Plasminogen, 110 Platelet-derived growth factor (PDGF), 241 Platelet-rich plasma (PRP) ACL healing, age and skeletal maturity effect, biological scaffolds biologic adjunct, 210 clinical studies, 209 orthopedics, 209 surgery, vs.collagen scaffold, concentration, 245, 246 in vivo model, use of,

8 316 Platelet-rich plasma (PRP) (cont.) vs. non-prp group, porcine model, 270 preparation, ovine, 151 Platelets activation of, 240 aggregating, 243 concentration 3 and 5 PRP produce, 245, 246 bone healing, 246 dose response relationship, 245 PRP, 245 growth factors association, 242 release, 240 in vivo model, complete ACL tear absorbable vs. nonabsorbable sutures, 235 carrier alone vs., delivery of, and ECM-based scaffold, platelet carrier, stimulation of, PRP use, selection and validation, surgical technique improvement, suture technique, physiological conditions, 239 platelet-rich plasma and ACL healing, definition, growth factor receptor expression, 244 growth factors associated, 242 with red blood cells, 240 wound healing megakaryocyte, 77 number vs. growth factor release, 77 role, 76 Polymerase chain reaction (PCR), 185 Polytetrafluoroethylene (PTFE) graft, Preclinical models advantages, biomechanics, 186 R Red blood cells (RBCs) ligament healing CD163, 251 effect of, 252 fibroblast proliferation, 250 inflammation, role, wound repair, 250 wound healing, 78 Reinnervation. See also Wound healing after ACL reconstruction, enhanced ACL repair, 281 Revascularization. See also Wound healing after ACL reconstruction, 279 enhanced ACL repair, 281 response, impaired healing, 103 Rolimeter, 196 Rotator cuff tendon, 170 S Scratch test, 130 Skeletal maturity effect. See Age and skeletal maturity effect, ACL healing Stretchability, ACL, 65, 66 Synthetic materials, ACL poly(l-lactic acid) (PLLA), 206 PTFE graft, T Tensile failure testing, 187 TERM. See Tissue Engineering and Regenerative Medicine (TERM) Thrombocytes. See Platelets Thromboxane A2 (TXA2), 76 Tissue engineering ACL treatment, biological scaffolds, 203 biomaterial, choice collagen, polymers advantage, 172 cell sources cartilage repair procedures, 170 MPC differentiation, 171 clinical approaches bio-artificial, 174 enhanced ACL repair, 175 primary repair enhance, 174 stress shielding, 173 definition, 167 growth factors, healthy ligaments crimp, 169 provisional scaffold, 170 tears, 170 outcome assessment ACL, 181 biochemistry and molecular biology, biomechanical evaluation, healing ligament, definition, 181

9 317 end result cards, 180 histology, human trials, in vitro phase, joint function, biomechanical evaluation, knee scores, 197 patient care improvement, preclinical models testing, signaling molecules, 172 triad of, 168 uses, 176 Tissue Engineering and Regenerative Medicine (TERM), T lymphocytes, ligament healing chronic inflammatory processes, 260 skin wound healing, tendon-bone healing, 259 Transforming growth factor beta (TGF-beta), 241 Translational medicine aims, 118 barriers clinicians vs. experts, language, 120 industry, 121 petri dish research, 121 regulatory framework, 120 clinical trial phase 1, phase 2, 119 phase 3, 119 definition, 115 gene therapy and stem cells use, 117 TERM, T1 T2 dilemma, two-way principle, 116 T suppressor lymphocytes, 83 TXA2. See Thromboxane A2 (TXA2) V Vascular endothelial growth factor (VEGF), 241 Visual analog scale (VAS), 193 W White blood cells, wound healing anabolic effects, 79 diapedesis, ligament healing, 252 photomicrograph, 79 tissue injury, 80 Wolff s law, Wound healing. See also Impaired healing, joint issues crucial role, extra-articular, 106 goal, 73 granulocytes basophils, 81 eosinophils, 81 neutrophils, 80, 81 inflammatory phase, initial processes, 75 intra-articular, in vitro models cells alone, 130 cells and biomaterials, high-density cell culture, 131, 132 the scratch test, 130 lymphocytes, mechanoreceptors, 276 monocytes and macrophages, nerves and blood vessels ACL after injury, 277 after ACL reconstruction, after bio-enhanced ACL repair, healing response, 278 roles, 281 nerve structures, Pacinian corpuscle, 276 partial ACL tears, 218, 222 platelets, (see also Platelets) principal phases of, 74 proliferative phase fibroblasts, outcome, 84 red blood cells, 78 reflex arcs, knee, 274, 276 reinnervation (see Reinnervation) remodeling phase, revascularization (see Revascularization) Ruffini corpuscles, 275 structures, 275 synovial tissue, nerve fibers, 275 tendon graft, 274 thromboxane A2 (TXA2), 76 timing of cellular involvement, 86 white blood cells, 78 80