The effect of genetically modified platelet-derived growth factor-BB over-expressing mesenchymal stromal cells during core decompression for steroid-associated osteonecrosis of the femoral head in rabbits.

BACKGROUND: Approximately one third of patients undergoing core decompression (CD) for early-stage osteonecrosis of the femoral head (ONFH) experience progression of the disease, and subsequently require total hip arthroplasty (THA). Thus, identifying adjunctive treatments to optimize bone regeneration during CD is an unmet clinical need. Platelet-derived growth factor (PDGF)-BB plays a central role in cell growth and differentiation. The aim of this study was to characterize mesenchymal stromal cells (MSCs) that were genetically modified to overexpress PDGF-BB (PDGF-BB-MSCs) in vitro and evaluate their therapeutic effect when injected into the bone tunnel at the time of CD in an in vivo rabbit model of steroid-associated ONFH. METHODS: In vitro studies: Rabbit MSCs were transduced with a lentivirus vector carrying the human PDGF-BB gene under the control of either the cytomegalovirus (CMV) or phosphoglycerate (PGK) promoter. The proliferative rate, PDGF-BB expression level, and osteogenic differentiation capacity of unmodified MSCs, CMV-PDGF-BB-MSCs, and PGK-PDGF-BB-MSCs were assessed. In vivo studies: Twenty-four male New Zealand white rabbits received an intramuscular (IM) injection of methylprednisolone 20 mg/kg. Four weeks later, the rabbits were divided into four groups: the CD group, the hydrogel [HG, (a collagen-alginate mixture)] group, the MSC group, and the PGK-PDGF-BB-MSC group. Eight weeks later, the rabbits were sacrificed, their femurs were harvested, and microCT, mechanical testing, and histological analyses were performed. RESULTS: In vitro studies: PGK-PDGF-BB-MSCs proliferated more rapidly than unmodified MSCs (P < 0.001) and CMV-PDGF-BB-MSCs (P < 0.05) at days 3 and 7. CMV-PDGF-BB-MSCs demonstrated greater PDGF-BB expression than PGK-PDGF-BB-MSCs (P < 0.01). However, PGK-PDGF-BB-MSCs exhibited greater alkaline phosphatase staining at 14 days (P < 0.01), and osteogenic differentiation at 28 days (P = 0.07) than CMV-PDGF-BB-MSCs. In vivo: The PGK-PDGF-BB-MSC group had a trend towards greater bone mineral density (BMD) than the CD group (P = 0.074). The PGK-PDGF-BB-MSC group demonstrated significantly lower numbers of empty lacunae (P < 0.001), greater osteoclast density (P < 0.01), and greater angiogenesis (P < 0.01) than the other treatment groups. CONCLUSION: The use of PGK-PDGF-BB-MSCs as an adjunctive treatment with CD may reduce progression of osteonecrosis and enhance bone regeneration and angiogenesis in the treatment of early-stage ONFH.

Supplemental medial small fragment fixation adds stability to distal femur fixation: A biomechanical study.

INTRODUCTION: Bridge plating of distal femur fractures with lateral locking plates is susceptible to varus collapse, fixation failure, and nonunion. While medial and lateral dual plating has been described in clinical series, the biomechanical effects of dual plating of distal femur fractures have yet to be clearly defined. The purpose of this study was to compare dual plating to lateral locked bridge plating alone in a cadaveric distal femur gap osteotomy model. MATERIALS AND METHODS: Gap osteotomies were created in eight matched pairs of cadaveric female distal femurs (average age: 64 yrs (standard deviation ± 4.4 yrs); age range: 57-68 yrs;) to simulate comminuted extraarticular distal femur fractures (AO/OTA 33A). Eight femurs underwent fixation with lateral locked plates alone and were matched with eight femurs treated with dual plating: lateral locked plates with supplemental medial small fragment non-locking fixation. Mechanical testing was performed on an ElectroPuls E10000 materials testing system using a 10 kN/100 Nm biaxial load cell. Specimens were subject to 25,000 cycles of cyclic loading from 100-1000 N at 2 Hz. RESULTS: Two (2/8) specimens in the lateral only group failed catastrophically prior to completion of testing. All dual plated specimens survived the testing regimen. Dual plated specimens demonstrated significantly less coronal plane displacement (median 0.2 degrees, interquartile range [IQR], 0.0-0.5 degrees) compared to 2.0 degrees (IQR 1.9-3.3, p = 0.02) in the lateral plate only group. Dual plated specimens demonstrated greater bending stiffness compared to the lateral plated group (median 29.0 kN/degree, IQR 1.5-68.2 kN/degree vs median 0.50 kN/degree, IQR 0.23-2.28 kN/degree, p = 0.03). CONCLUSION: Contemporary fixation methods with a distal femur fractures are susceptible to mechanical failure and nonunion with lateral plates alone. Dual plate fixation in a cadaveric model of distal femur fractures underwent significantly less displacement under simulated weight bearing conditions and demonstrated greater stiffness than lateral plating alone. Given the significant clinical failure rates of lateral bridge plating in distal femur fractures, supplemental fixation should be considered, and dual plating of distal femurs augments mechanical stability in a clinically relevant magnitude.

The Effect of Resection Size in the Treatment of Cam-Type Femoroacetabular Impingement in the Typical Patient With Hip Arthroscopy: A Biomechanical Analysis.

BACKGROUND: Arthroscopic osteochondroplasty may improve range of motion and relieve pain in patients with symptomatic hip impingement. Femoral neck fracture is a risk of this procedure because of the weakening of the proximal femur. To our knowledge, there are no biomechanical studies in young human cadaveric bone evaluating the effect of osteochondroplasty on femoral neck strength. PURPOSE/HYPOTHESIS: The purpose was to evaluate loads to fracture in young human cadavers after resection depths of 25% and 40% at the head-neck junction. We hypothesized that both depths will maintain ultimate loads to failure above previously published loads, as well as above physiologic weightbearing loads. STUDY DESIGN: Descriptive laboratory study. METHODS: Cadaveric proximal femoral specimens (6 matched pairs, under the age of 47 years) were divided into 2 groups: 25% or 40% of the diameter at the head-neck junction was resected. The length of the resection was 2 cm and the width of the resection was determined by the length of the anterolateral quadrant at the head-neck junction in all cases. A compressive load was applied directly to the femoral head. Peak load, stiffness, and energy to fracture were compared between groups. RESULTS: The average peak load to fracture after 25% resection (7347 N) was significantly higher than after the 40% resection (5892 N) (P = .010). The average energy to fracture was also significantly higher in the 25% resection group (30.2 J vs 19.2 J; P = .007). The average stiffness was higher in the 25% group, although not statistically significant (P = .737). CONCLUSION: Resection depths of 25% and 40% at the anterolateral quadrant of the femoral head-neck junction may be safe at previously described functional loads such as standing and walking in the age range more typically seen in patients undergoing hip arthroscopy. Loads to fracture were significantly higher than previously reported using older cadaveric specimens. CLINICAL RELEVANCE: Currently, most surgeons limit weightbearing after femoral osteochondroplasty in part because of risk of femoral neck fracture. Given the higher observed loads to fracture, young patients could possibly bear weight sooner after surgery, although postoperative protocols should be individualized based on patient age, weight, bone density, amount of bone resected, concomitant procedures, and potential compliance with activity restrictions.