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Nadim J Hallab

TitleProfessor
InstitutionRush University, Rush Medical College
DepartmentOrthopedic Surgery
Address1611 W. Harrison St.
Chicago IL 60612
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    Adjunct Professor, Department of Immunity and Emerging Pathogen

    Overview:
    Dr. Hallab’s research involves the study of implant degradation and biologic reactivity to soluble and particulate implant debris with four areas of focus: 1) Immune reactivity to implant debris, from both an adaptive (T-cell) and innate (macrophage) perspective, 2) Implant connections (modular junctions) and implant fretting corrosion, metal release and metal-protein complex formation, 3) Peri-implant cell toxicity responses to implant degradation products such as metals, 4) Study of how material surfaces can be used to control immune and cell function such as bone deposition. Over the years his group has found different types of implant debris (ions vs particles) bind to different specific serum proteins in people with total joint replacements, these differences translate into quantifiable person- and material-specific immune responses that can be used as diagnostic measures of performance. His research has dealt with the engineering aspects of implant degradation (wear and corrosion) and innate/adaptive immune responses to implant debris. He has discovered how metal implant debris induces inflammasome danger signaling and how DTH responses to implants metal depend on both the innate and adaptive immune system. His group has been at the for front of discovery in this field of improving implant performance over the past 20 years and reported that implant metals induce person-dependent monocyte-macrophage activation, where metals such as Cobalt ions and Co-Cr-Mo alloy particles were found to consistently induced inflammasome dependent co-stimulatory molecule increases, lysosome destabilization, hypoxia type responses, and increased DTH immune responses in prospective THA cohorts. Additnionally, he has developed methods for diagnosing metal sensitivity that are being used clinically to help people with or receiving orthopedic implants. They have quantified toxicity responses of many implant metals (e.g. Al, Co, Cr, Cu, Fe, Mo Nb, Ni and Zr) to peri-implant cells. These areas are focused on the continuing mission of his lab to improve implant performance through increased knowledge of person-dependent immune-implant debris interactions.

    My ORCID is 0000-0001-6421-2836.
    My Scopus ID is 7004113864.
    MY NIH COMMONS name is nhallab.

    Education:
    PhD, Tulane University (Biomedical Engineering)
    MS, Texas A&M University (Mechanical Engineering)
    BS, Texas A&M University (Mechanical Engineering)

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    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    1. Caicedo MS, Flores V, Siapno R, Crosby M, Samelko LA, Jacobs JJ, Hallab NJ. Establishing clinically meaningful ranges of metal hypersensitivity in orthopaedic patients using COVID-19 vaccine-induced adaptive immune responses from fully vaccinated adults. J Orthop. 2024 Feb; 48:89-95. PMID: 38089694.
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    2. Caicedo MS, Flores V, Padilla A, Lauryn S, Jacobs JJ, Hallab NJ. COVID-19 (SARS-CoV-2) lymphocyte responses are associated with inflammatory biomarkers in total joint replacement surgery candidates pre-operatively. J Orthop Surg Res. 2021 Jun 30; 16(1):415. PMID: 34193239.
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    3. Royhman D, Pourzal R, Hall D, Lundberg HJ, Wimmer MA, Jacobs J, Hallab NJ, Mathew MT. Fretting-corrosion in hip taper modular junctions: The influence of topography and pH levels - An in-vitro study. J Mech Behav Biomed Mater. 2021 06; 118:104443. PMID: 33752094.
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    4. Mishra PK, Palma M, Buechel B, Moore J, Davra V, Chu N, Millman A, Hallab NJ, Kanneganti TD, Birge RB, Behrens EM, Rivera A, Beebe KS, Benevenia J, Gause WC. Sterile particle-induced inflammation is mediated by macrophages releasing IL-33 through a Bruton's tyrosine kinase-dependent pathway. Nat Mater. 2019 03; 18(3):289-297. PMID: 30664693.
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    5. Singh V, Rawlinson J, Hallab N. Stainless steel wear debris of a scoliotic growth guidance system has little local and systemic effect in an animal model. J Orthop Res. 2018 07; 36(7):1980-1990. PMID: 29323741.
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    6. Royhman D, Patel M, Jacobs JJ, Wimmer MA, Hallab NJ, Mathew MT. In vitro simulation of fretting-corrosion in hip implant modular junctions: The influence of pH. Med Eng Phys. 2018 02; 52:1-9. PMID: 29290499.
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    7. Caicedo MS, Solver E, Coleman L, Jacobs JJ, Hallab NJ. Females with Unexplained Joint Pain Following Total Joint Arthroplasty Exhibit a Higher Rate and Severity of Hypersensitivity to Implant Metals Compared with Males: Implications of Sex-Based Bioreactivity Differences. J Bone Joint Surg Am. 2017 Apr 19; 99(8):621-628. PMID: 28419029.
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    8. Hallab NJ, Jacobs JJ. Chemokines Associated with Pathologic Responses to Orthopedic Implant Debris. Front Endocrinol (Lausanne). 2017; 8:5. PMID: 28154552.
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    9. Samelko L, Landgraeber S, McAllister K, Jacobs J, Hallab NJ. Cobalt Alloy Implant Debris Induces Inflammation and Bone Loss Primarily through Danger Signaling, Not TLR4 Activation: Implications for DAMP-ening Implant Related Inflammation. PLoS One. 2016; 11(7):e0160141. PMID: 27467577.
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    10. Royhman D, Patel M, Runa MJ, Wimmer MA, Jacobs JJ, Hallab NJ, Mathew MT. Fretting-corrosion behavior in hip implant modular junctions: The influence of friction energy and pH variation. J Mech Behav Biomed Mater. 2016 09; 62:570-587. PMID: 27310572.
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    11. Chen Y, Hallab NJ, Liao YS, Narayan V, Schwarz EM, Xie C. Antioxidant impregnated ultra-high molecular weight polyethylene wear debris particles display increased bone remodeling and a superior osteogenic:osteolytic profile vs. conventional UHMWPE particles in a murine calvaria model. J Orthop Res. 2016 05; 34(5):845-51. PMID: 26495749.
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    12. Kanaji A, Orhue V, Caicedo MS, Virdi AS, Sumner DR, Hallab NJ, Yoshiaki T, Sena K. Cytotoxic effects of cobalt and nickel ions on osteocytes in vitro. J Orthop Surg Res. 2014 Oct 08; 9:91. PMID: 25288055.
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    13. Caicedo MS, Solver E, Coleman L, Hallab NJ. Metal sensitivities among TJA patients with post-operative pain: indications for multi-metal LTT testing. J Long Term Eff Med Implants. 2014; 24(1):37-44. PMID: 24941404.
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    14. Hsu AR, Levine BR, Skipor AK, Hallab NJ, Paprosky WG, Jacobs JJ. Effect of a second joint arthroplasty on metal ion levels after primary total hip arthroplasty. Am J Orthop (Belle Mead NJ). 2013 Oct; 42(10):E84-7. PMID: 24278909.
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    15. Singh V, Simpson J, Rawlinson J, Hallab N. Growth guidance system for early-onset scoliosis: comparison of experimental and retrieval wear. Spine (Phila Pa 1976). 2013 Aug 15; 38(18):1546-53. PMID: 23656961.
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    16. Levine BR, Hsu AR, Skipor AK, Hallab NJ, Paprosky WG, Galante JO, Jacobs JJ. Ten-year outcome of serum metal ion levels after primary total hip arthroplasty: a concise follow-up of a previous report*. J Bone Joint Surg Am. 2013 Mar 20; 95(6):512-8. PMID: 23515985.
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    17. Hallab NJ, Caicedo M, McAllister K, Skipor A, Amstutz H, Jacobs JJ. Asymptomatic prospective and retrospective cohorts with metal-on-metal hip arthroplasty indicate acquired lymphocyte reactivity varies with metal ion levels on a group basis. J Orthop Res. 2013 Feb; 31(2):173-82. PMID: 22941579.
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    18. Mathew MT, Abbey S, Hallab NJ, Hall DJ, Sukotjo C, Wimmer MA. Influence of pH on the tribocorrosion behavior of CpTi in the oral environment: synergistic interactions of wear and corrosion. J Biomed Mater Res B Appl Biomater. 2012 Aug; 100(6):1662-71. PMID: 22707174.
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    19. Dalal A, Pawar V, McAllister K, Weaver C, Hallab NJ. Orthopedic implant cobalt-alloy particles produce greater toxicity and inflammatory cytokines than titanium alloy and zirconium alloy-based particles in vitro, in human osteoblasts, fibroblasts, and macrophages. J Biomed Mater Res A. 2012 Aug; 100(8):2147-58. PMID: 22615169.
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    20. Mishra PK, Wu W, Rozo C, Hallab NJ, Benevenia J, Gause WC. Micrometer-sized titanium particles can induce potent Th2-type responses through TLR4-independent pathways. J Immunol. 2011 Dec 15; 187(12):6491-8. PMID: 22095717.
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    21. Orhue V, Kanaji A, Caicedo MS, Virdi AS, Sumner DR, Hallab NJ, Jahr H, Sena K. Calcineurin/nuclear factor of activated T cells (NFAT) signaling in cobalt-chromium-molybdenum (CoCrMo) particles-induced tumor necrosis factor-a (TNFa) secretion in MLO-Y4 osteocytes. J Orthop Res. 2011 Dec; 29(12):1867-73. PMID: 21557302.
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    22. Deirmengian C, Hallab N, Tarabishy A, Della Valle C, Jacobs JJ, Lonner J, Booth RE. Synovial fluid biomarkers for periprosthetic infection. Clin Orthop Relat Res. 2010 Aug; 468(8):2017-23. PMID: 20300901.
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    23. Caicedo MS, Pennekamp PH, McAllister K, Jacobs JJ, Hallab NJ. Soluble ions more than particulate cobalt-alloy implant debris induce monocyte costimulatory molecule expression and release of proinflammatory cytokines critical to metal-induced lymphocyte reactivity. J Biomed Mater Res A. 2010 Jun 15; 93(4):1312-21. PMID: 19844976.
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    24. Smith RA, Maghsoodpour A, Hallab NJ. In vivo response to cross-linked polyethylene and polycarbonate-urethane particles. J Biomed Mater Res A. 2010 Apr; 93(1):227-34. PMID: 19557792.
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    25. Caicedo MS, Desai R, McAllister K, Reddy A, Jacobs JJ, Hallab NJ. Soluble and particulate Co-Cr-Mo alloy implant metals activate the inflammasome danger signaling pathway in human macrophages: a novel mechanism for implant debris reactivity. J Orthop Res. 2009 Jul; 27(7):847-54. PMID: 19105226.
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    26. Kanaji A, Caicedo MS, Virdi AS, Sumner DR, Hallab NJ, Sena K. Co-Cr-Mo alloy particles induce tumor necrosis factor alpha production in MLO-Y4 osteocytes: a role for osteocytes in particle-induced inflammation. Bone. 2009 Sep; 45(3):528-33. PMID: 19497395.
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    27. Lee GH, Kumar A, Berkson E, Verma N, Bach BR, Hallab N. A biomechanical analysis of bone-patellar tendon-bone grafts after repeat freeze-thaw cycles in a cyclic loading model. J Knee Surg. 2009 Apr; 22(2):111-3. PMID: 19476174.
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    28. Jacobs JJ, Urban RM, Hallab NJ, Skipor AK, Fischer A, Wimmer MA. Metal-on-metal bearing surfaces. J Am Acad Orthop Surg. 2009 Feb; 17(2):69-76. PMID: 19202120.
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    29. Hallab NJ, Jacobs JJ. Biologic effects of implant debris. Bull NYU Hosp Jt Dis. 2009; 67(2):182-8. PMID: 19583551.
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    30. Caicedo M, Jacobs JJ, Reddy A, Hallab NJ. Analysis of metal ion-induced DNA damage, apoptosis, and necrosis in human (Jurkat) T-cells demonstrates Ni2+ and V3+ are more toxic than other metals: Al3+, Be2+, Co2+, Cr3+, Cu2+, Fe3+, Mo5+, Nb5+, Zr2+. J Biomed Mater Res A. 2008 Sep 15; 86(4):905-13. PMID: 18050301.
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    31. Scuderi GJ, Brusovanik GV, Golish SR, Demeo R, Hyde J, Hallab N, Vaccaro AR. A critical evaluation of discography in patients with lumbar intervertebral disc disease. Spine J. 2008 Jul-Aug; 8(4):624-9. PMID: 18069067.
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    32. Jacobs JJ, Hallab NJ. Loosening and osteolysis associated with metal-on-metal bearings: A local effect of metal hypersensitivity? J Bone Joint Surg Am. 2006 Jun; 88(6):1171-2. PMID: 16757747.
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    33. Buvanendran A, Kroin JS, Berger RA, Hallab NJ, Saha C, Negrescu C, Moric M, Caicedo MS, Tuman KJ. Upregulation of prostaglandin E2 and interleukins in the central nervous system and peripheral tissue during and after surgery in humans. Anesthesiology. 2006 Mar; 104(3):403-10. PMID: 16508385.
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    34. De Ranieri A, Virdi AS, Kuroda S, Healy KE, Hallab NJ, Sumner DR. Saline irrigation does not affect bone formation or fixation strength of hydroxyapatite/tricalcium phosphate-coated implants in a rat model. J Biomed Mater Res B Appl Biomater. 2005 Aug; 74(2):712-7. PMID: 15988751.
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    35. De Ranieri A, Virdi AS, Kuroda S, Shott S, Leven RM, Hallab NJ, Sumner DR. Local application of rhTGF-beta2 enhances peri-implant bone volume and bone-implant contact in a rat model. Bone. 2005 Jul; 37(1):55-62. PMID: 15869922.
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    36. Hallab NJ, Anderson S, Caicedo M, Skipor A, Campbell P, Jacobs JJ. Immune responses correlate with serum-metal in metal-on-metal hip arthroplasty. J Arthroplasty. 2004 Dec; 19(8 Suppl 3):88-93. PMID: 15578560.
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    37. Hallab NJ, Messina C, Skipor A, Jacobs JJ. Differences in the fretting corrosion of metal-metal and ceramic-metal modular junctions of total hip replacements. J Orthop Res. 2004 Mar; 22(2):250-9. PMID: 15013082.
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    38. Jacobs JJ, Hallab NJ, Skipor AK, Urban RM. Metal degradation products: a cause for concern in metal-metal bearings? Clin Orthop Relat Res. 2003 Dec; (417):139-47. PMID: 14646711.
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    39. Hallab N, Link HD, McAfee PC. Biomaterial optimization in total disc arthroplasty. Spine (Phila Pa 1976). 2003 Oct 15; 28(20):S139-52. PMID: 14560185.
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    40. Verma N, Noerdlinger MA, Hallab N, Bush-Joseph CA, Bach BR. Effects of graft rotation on initial biomechanical failure characteristics of bone-patellar tendon-bone constructs. Am J Sports Med. 2003 Sep-Oct; 31(5):708-13. PMID: 12975190.
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    41. Cunningham BW, Orbegoso CM, Dmitriev AE, Hallab NJ, Sefter JC, Asdourian P, McAfee PC. The effect of spinal instrumentation particulate wear debris. an in vivo rabbit model and applied clinical study of retrieved instrumentation cases. Spine J. 2003 Jan-Feb; 3(1):19-32. PMID: 14589241.
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    42. Cunningham BW, Orbegoso CM, Dmitriev AE, Hallab NJ, Sefter JC, McAfee PC. The effect of titanium particulate on development and maintenance of a posterolateral spinal arthrodesis: an in vivo rabbit model. Spine (Phila Pa 1976). 2002 Sep 15; 27(18):1971-81. PMID: 12634556.
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    43. Hallab NJ, Vermes C, Messina C, Roebuck KA, Glant TT, Jacobs JJ. Concentration- and composition-dependent effects of metal ions on human MG-63 osteoblasts. J Biomed Mater Res. 2002 Jun 05; 60(3):420-33. PMID: 11920666.
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    44. Vermes C, Glant TT, Hallab NJ, Fritz EA, Roebuck KA, Jacobs JJ. The potential role of the osteoblast in the development of periprosthetic osteolysis: review of in vitro osteoblast responses to wear debris, corrosion products, and cytokines and growth factors. J Arthroplasty. 2001 Dec; 16(8 Suppl 1):95-100. PMID: 11742458.
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    45. Jacobs JJ, Roebuck KA, Archibeck M, Hallab NJ, Glant TT. Osteolysis: basic science. Clin Orthop Relat Res. 2001 Dec; (393):71-7. PMID: 11764373.
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    46. Hallab N. Metal sensitivity in patients with orthopedic implants. J Clin Rheumatol. 2001 Aug; 7(4):215-8. PMID: 17039137.
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    47. Hallab NJ, Mikecz K, Vermes C, Skipor A, Jacobs JJ. Orthopaedic implant related metal toxicity in terms of human lymphocyte reactivity to metal-protein complexes produced from cobalt-base and titanium-base implant alloy degradation. Mol Cell Biochem. 2001 Jun; 222(1-2):127-36. PMID: 11678594.
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    48. Hallab NJ, Bundy KJ, O'Connor K, Moses RL, Jacobs JJ. Evaluation of metallic and polymeric biomaterial surface energy and surface roughness characteristics for directed cell adhesion. Tissue Eng. 2001 Feb; 7(1):55-71. PMID: 11224924.
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    49. Hallab NJ, Mikecz K, Jacobs JJ. A triple assay technique for the evaluation of metal-induced, delayed-type hypersensitivity responses in patients with or receiving total joint arthroplasty. J Biomed Mater Res. 2000 Sep; 53(5):480-9. PMID: 10984695.
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    50. Hallab N, Jacobs JJ, Black J. Hypersensitivity to metallic biomaterials: a review of leukocyte migration inhibition assays. Biomaterials. 2000 Jul; 21(13):1301-14. PMID: 10850924.
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    51. Jacobs JJ, Silverton C, Hallab NJ, Skipor AK, Patterson L, Black J, Galante JO. Metal release and excretion from cementless titanium alloy total knee replacements. Clin Orthop Relat Res. 1999 Jan; (358):173-80. PMID: 9973989.
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    52. Hallab NJ, Bundy KJ, O'Connor K, Clark R, Moses RL. Cell adhesion to biomaterials: correlations between surface charge, surface roughness, adsorbed protein, and cell morphology. J Long Term Eff Med Implants. 1995; 5(3):209-31. PMID: 10172729.
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