Internal Fixation Construct and Defect Size Affect Healing of a Translational Porcine Diaphyseal Tibial Segmental Bone Defect.


Journal

Military medicine
ISSN: 1930-613X
Titre abrégé: Mil Med
Pays: England
ID NLM: 2984771R

Informations de publication

Date de publication:
02 11 2021
Historique:
received: 16 09 2020
revised: 04 11 2020
accepted: 18 11 2020
pubmed: 27 11 2020
medline: 12 11 2021
entrez: 26 11 2020
Statut: ppublish

Résumé

Porcine translational models have become the gold-standard translational tool to study the effects of major injury and hemorrhagic shock because of their similarity to the human immunologic response to trauma. Segmental bone defects (SBDs) typically occur in warfighters with associated severe limb trauma. The purpose of this study was to develop a translational porcine diaphyseal SBD model in Yucatan minipigs (YMPs), which could be used in bone healing investigations that simulate injury-relevant conditions. We were specifically working toward developing a critical sized defect (CSD). We used an adaptive experimental design in which both 25.0 mm and 40.0 mm SBDs were created in the tibial mid-diaphysis in skeletally mature YMPs. Initially, eight YMPs were subjected to a 25.0 mm SBD and treated with intramedullary nailing (intramedullary nail [IMN] 25mm). Due to unanticipated wound problems, we subsequently treated four specimens with identical 25.0 mm defect with dual plating (open reduction with internal fixation [ORIF] 25mm). Finally, a third group of four YMPs with 40.0 mm defects were treated with dual plating (ORIF 40mm). Monthly radiographs were made until sacrifice. Modified Radiographic Union Score for Tibia fractures (mRUST) measurements were made by three trauma-trained orthopedic surgeons. CT scans of the tibias were used to verify the union results. At 4 months post-surgery, mean mRUST scores were 11.7 (SD ± 1.8) in the ORIF 25mm YMPs vs. 8.5 (SD  ± 1.4) in the IMN 25mm YMPs (P < .0001). All four ORIF 25mm YMPs were clinically healed. In contrast, none of the IMN 25mm YMPs were clinically healed and seven of eight IMN 25mm YMPs developed delayed wound breakdown. All four of the ORIF 40mm YMPs had flail nonunions with complete hardware failure by 3 months after surgery and were sacrificed early. CT scanning confirmed that none of the IMN 25mm YMPs, none of the ORIF 40mm YMPs, and two of four ORIF 25mm YMPs were healed. A third ORIF 25mm specimen was nearly healed on CT scanning. Inter-rater and intra-rater reliability interclass coefficients using the mRUST scale were 0.81 and 0.80, respectively. YMPs that had a 40 mm segment of bone removed from their tibia and were treated with dual plating did not heal and could be used to investigate interventions that accelerate bone healing. In contrast, a 25 mm SBD treated with dual plating demonstrated delayed but successful healing, indicating it can potentially be used to investigate bone healing adjuncts or conversely how concomitant injuries may impair bone healing. Pigs treated with IMN failed to heal and developed consistent delayed wound breakdown presumably secondary to chronic limb instability. The porcine YMP SBD model has the potential to be an effective translational tool to investigate bone healing under physiologically relevant injury conditions.

Sections du résumé

BACKGROUND AND OBJECTIVE
Porcine translational models have become the gold-standard translational tool to study the effects of major injury and hemorrhagic shock because of their similarity to the human immunologic response to trauma. Segmental bone defects (SBDs) typically occur in warfighters with associated severe limb trauma. The purpose of this study was to develop a translational porcine diaphyseal SBD model in Yucatan minipigs (YMPs), which could be used in bone healing investigations that simulate injury-relevant conditions. We were specifically working toward developing a critical sized defect (CSD).
METHODS
We used an adaptive experimental design in which both 25.0 mm and 40.0 mm SBDs were created in the tibial mid-diaphysis in skeletally mature YMPs. Initially, eight YMPs were subjected to a 25.0 mm SBD and treated with intramedullary nailing (intramedullary nail [IMN] 25mm). Due to unanticipated wound problems, we subsequently treated four specimens with identical 25.0 mm defect with dual plating (open reduction with internal fixation [ORIF] 25mm). Finally, a third group of four YMPs with 40.0 mm defects were treated with dual plating (ORIF 40mm). Monthly radiographs were made until sacrifice. Modified Radiographic Union Score for Tibia fractures (mRUST) measurements were made by three trauma-trained orthopedic surgeons. CT scans of the tibias were used to verify the union results.
RESULTS
At 4 months post-surgery, mean mRUST scores were 11.7 (SD ± 1.8) in the ORIF 25mm YMPs vs. 8.5 (SD  ± 1.4) in the IMN 25mm YMPs (P < .0001). All four ORIF 25mm YMPs were clinically healed. In contrast, none of the IMN 25mm YMPs were clinically healed and seven of eight IMN 25mm YMPs developed delayed wound breakdown. All four of the ORIF 40mm YMPs had flail nonunions with complete hardware failure by 3 months after surgery and were sacrificed early. CT scanning confirmed that none of the IMN 25mm YMPs, none of the ORIF 40mm YMPs, and two of four ORIF 25mm YMPs were healed. A third ORIF 25mm specimen was nearly healed on CT scanning. Inter-rater and intra-rater reliability interclass coefficients using the mRUST scale were 0.81 and 0.80, respectively.
CONCLUSIONS
YMPs that had a 40 mm segment of bone removed from their tibia and were treated with dual plating did not heal and could be used to investigate interventions that accelerate bone healing. In contrast, a 25 mm SBD treated with dual plating demonstrated delayed but successful healing, indicating it can potentially be used to investigate bone healing adjuncts or conversely how concomitant injuries may impair bone healing. Pigs treated with IMN failed to heal and developed consistent delayed wound breakdown presumably secondary to chronic limb instability. The porcine YMP SBD model has the potential to be an effective translational tool to investigate bone healing under physiologically relevant injury conditions.

Identifiants

pubmed: 33242094
pii: 6006802
doi: 10.1093/milmed/usaa516
pmc: PMC8902946
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1115-e1123

Subventions

Organisme : NIAMS NIH HHS
ID : P30 AR072581
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL091816
Pays : United States
Organisme : NHLBI NIH HHS
ID : T35 HL110854
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002529
Pays : United States

Commentaires et corrections

Type : ErratumIn

Informations de copyright

© The Association of Military Surgeons of the United States 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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Auteurs

Todd O McKinley (TO)

Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Roman M Natoli (RM)

Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

James P Fischer (JP)

Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Jeffrey D Rytlewski (JD)

Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA 52240, USA.

David C Scofield (DC)

Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Rashad Usmani (R)

Department of Orthopaedic Surgery, University of Louisville School of Medicine, Louisville, KY 40202, USA.

Alexander Kuzma (A)

Department of Orthopaedic Surgery, University of Kentucky School of Medicine, Lexington, KY 40506, USA.

Kaitlyn S Griffin (KS)

Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.

Emily Jewell (E)

Department of Orthopaedic Surgery, University of North Carolina School of Medicine, Chapel Hill, NC 27516, USA.

Paul Childress (P)

Anagin Incorporated, Noyes Pavilion, Indianapolis, IN 46202, USA.

Karl D Shively (KD)

Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Tien-Min Gabriel Chu (TG)

Indiana University School of Dentistry, Indianapolis, IN 46202, USA.

Jeffrey O Anglen (JO)

Sadhana Boneworks, Indianapolis, IN 46220, USA.

Melissa A Kacena (MA)

Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

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