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

Abstract

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.

Minced muscle autografting improves bone healing but not muscle function in a porcine composite injury model

“…These methods maintained the dimensions of the SBD and anatomic alignment of the tibia (Figure 1A). 16,17 …”

“…[13][14][15] In other work, we have developed an isolated porcine SBD model, which results in slow but consistent healing of a 25.0 mm defect in the mid-diaphysis of the tibia. 16,17 The purpose of this study was to combine our VML and SBD injury models into a porcine CTI model in Yucatan Minipigs (YMPs).…”

In vitro analysis and in vivo assessment of fracture complications associated with use of locking plate constructs for stabilization of caprine tibial segmental defects

“…Factors such as excessive bone loss, unfavorable healing environment, systemic disease, and biomechanical instability in long bone fracture fixation cases can lead to the formation of large defects with limited regenerative capability [ 25 ]. The risk of malunion or nonunion complications resulting in segmental defects pose innumerable surgical, socio-economic, and research challenges, and current standard treatment options are limited, sometimes necessitating limb amputation [ 20 , 25 ]. In people, the tibial shaft is the most common site for segmental defects due to its size, relative lack of soft tissue coverage, and relatively frequent incidence of fracture [ 7 , 25 ].…”

“…The most relevant species utilized for translational long bone segmental defect modeling are dogs, sheep, goats, and pigs. These species demonstrate physiologic and pathophysiologic similarities to humans in terms of long bone composition and healing, but models utilizing dogs and pigs have declined due to public concerns and limitations in handling and behavior [ 19 , 20 ]. Goats are a preferred model for translational orthopedic studies due to their trainability, cost-effectiveness, and translational characteristics including body weight, long bone dimensions, bone mineral composition, metabolic rate, and bone remodeling rate compared to humans [ 19 , 25 ].…”

“…Due to its stability and suitability for tissue engineering and bone biomaterial research, locking compression plate fixation has gained widespread use in bone segmental defect models [ 20 , 25 ]. However, questions regarding risk factors for locking plate implant failure and possible torsional instability persist, and relatively few studies have been published assessing complications associated with tibial locking plate gap stabilization, particularly in small ruminant species [ 6 , 11 , 26 ].…”