Carolyn M. Hettrich

The effect of matrix metalloproteinase inhibition on tendon-to-bone healing in a rotator cuff repair model

HYPOTHESISnRecent studies have demonstrated a potentially critical role of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in the pathophysiology of rotator cuff tears. We hypothesize that local delivery of a MMP inhibitor after surgical repair of the rotator cuff will improve healing at the tendon-to-bone surface interface.nnnMATERIALS AND METHODSnSixty-two male Sprague-Dawley rats underwent acute supraspinatus detachment and repair. In the control group (n=31), the supraspinatus was repaired to its anatomic footprint. In the experimental group (n=31), recombinant alpha-2-macroglobulin (A2M) protein, a universal MMP inhibitor, was applied at the tendon-bone interface with an identical surgical repair. Animals were sacrificed at 2 and 4 weeks for histomorphometry, immunohistochemistry, and biomechanical testing. Statistical comparisons were performed using unpaired t tests. Significance was set at P < .05.nnnRESULTSnSignificantly greater fibrocartilage was seen at the healing enthesis in the A2M-treated specimens compared with controls at 2 weeks (P < .05). Significantly greater collagen organization was observed in the A2M-treated animals compared with controls at 4 weeks (P < .01). A significant reduction in collagen degradation was observed at both 2 and 4 weeks in the experimental group (P < .05). Biomechanical testing revealed no significant differences in stiffness or ultimate load-to-failure.nnnCONCLUSIONnLocal delivery of an MMP inhibitor is associated with distinct histologic differences at the tendon-to-bone interface after rotator cuff repair. Modulation of MMP activity after rotator cuff repair may offer a novel biologic pathway to augment tendon-to-bone healing after rotator cuff repair.

Quantitative Assessment of the Vascularity of the Proximal Part of the Humerus

BACKGROUNDnThe current consensus in the literature is that the anterolateral branch of the anterior humeral circumflex artery provides the main blood supply to the humeral head. While the artery is disrupted in association with 80% of proximal humeral fractures, resultant osteonecrosis is infrequent. This inconsistency suggests a greater role for the posterior humeral circumflex artery than has been previously described. We hypothesized that the posterior humeral circumflex artery provides a greater percentage of perfusion to the humeral head than the anterior humeral circumflex artery does.nnnMETHODSnIn twenty-four fresh-frozen cadaver shoulders (twelve matched pairs), we cannulated the axillary artery proximal to the thoracoacromial branch and ligated the brachial artery in the forearm. In each pair, one shoulder served as a control with intact vasculature and, in the contralateral shoulder, either the anterior humeral circumflex artery or the posterior humeral circumflex artery was ligated. Gadolinium was injected through the cannulated axillary arteries, and magnetic resonance imaging was performed. After imaging, a urethane polymer was injected, and specimens were dissected. For volumetric analysis, the gadolinium uptake on the magnetic resonance imaging was quantified in each quadrant of the humeral head with use of a custom automated program. The gadolinium uptake was compared between the control and ligated sides and between the ligated anterior humeral circumflex artery and ligated posterior humeral circumflex artery groups.nnnRESULTSnThe posterior humeral circumflex artery provided 64% of the blood supply to the humeral head overall, whereas the anterior humeral circumflex artery supplied 36%. The posterior humeral circumflex artery also provided significantly more of the blood supply in three of the four quadrants of the humeral head.nnnCONCLUSIONSnThe finding that the posterior humeral circumflex artery provides 64% of the blood supply to the humeral head provides a possible explanation for the relatively low rates of osteonecrosis seen in association with displaced fractures of the proximal part of the humerus. In addition, protecting the posterior humeral circumflex artery during the surgical approach and fracture fixation may minimize loss of the blood supply to the humeral head.

Open reduction and internal fixation of tibial pilon fractures using a lateral approach

Objectives: To assess the wound complications and reductions achieved in a cohort of patients with pilon fractures who were treated using a novel lateral approach. Design: Retrospective review. Setting: Two level 1 trauma centers affiliated with academic institutions. Patients/Methods: All 44 fractures (in 43 patients) treated by the senior authors with open reduction and internal fixation (ORIF) using the lateral approach as the primary approach were included. Intervention: Data regarding medical comorbidities, mechanism of injury, soft-tissue injury sustained during the injury, treatment, wound healing, and secondary surgeries were recorded. Fractures were classified using the AO/OTA system with most being type C3. Eighteen fractures were open injuries (10 type 3). Fracture reductions were scored using the criteria of Teeny and Wiss. Main Outcome Measurements: Quality of articular reduction and soft-tissue healing. Results: An anatomic or good fracture reduction was achieved in 41 fractures (93%), and a fair reduction was obtained in 3 fractures. Two patients were successfully treated for deep infection (4.5%), and 2 patients developed a wound dehiscence (4.5%). There were no amputations. Twelve patients underwent secondary surgeries (27%). Five of these were for symptomatic screw removal (related to the fibular hardware in all cases), and the sixth was for planned removal of a syndesmotic-type screw (13.6%). Four were for nonunion, representing 9% of all cases. The remaining secondary surgeries (2 cases) were performed for infection. Overall, 13.6% of patients underwent a secondary surgical procedure to address nonunion or infection. Conclusions: When applied in a staged fashion, the lateral surgical approach for pilon fractures provides excellent protection of the soft-tissue envelopes by creating thick flaps while allowing excellent visualization for reconstruction of the anterior and lateral distal tibia.

Cartilage Repair: Third-generation Cell-based Technologies—basic Science, Surgical Techniques, Clinical Outcomes

The goal of all cartilage replacement techniques is the reformation of mature organized hyaline cartilage. However, currently cartilage repair techniques lead principally to production of fibrocartilage, which has material properties that are inferior to hyaline cartilage. Cell-based therapies such as autologous chondrocyte implantation hold promise for cartilage regeneration; however, these techniques still do not predictably result in hyaline cartilage formation. The newest, “third-generation techniques” have been developed to address the limitations of earlier techniques. These new procedures use 3 novel approaches: chondro-inductive or chondro-conductive matrix; use of allogeneic cells, both of which may allow a single-stage surgical approach; and techniques to mechanically condition the developing tissue before surgical application to improve the material properties and maturation of the implant. However, at this time there is very limited clinical data available on the nature and outcomes of these procedures.

Vascular Endothelial Growth Factor: An Essential Component of Angiogenesis and Fracture Healing

Fractures require adequate stability and blood supply to heal. The vascular supply to long bones is compromised in a fracture, and the ability to heal hinges on the ability of new blood vessels to proliferate from surrounding vessels in a process known as angiogenesis. This process is largely driven by the growth factor, vascular endothelial growth factor (VEGF), whose levels are increased locally and systemically during fracture healing. VEGF is involved in many steps throughout the fracture healing cascade, from initially being concentrated in fracture hematoma, to the promotion of bone turnover during the final remodeling phase. This article reviews the current literature surrounding the role of VEGF and other growth factors in reestablishing vascular supply to fractured bone, as well as medications and surgical techniques that may inhibit this process.

The effect of muscle paralysis using Botox on the healing of tendon to bone in a rat model.

HYPOTHESISnDespite good clinical results after rotator cuff repair, follow-up studies show significant rates of failed healing. This may be because of excessive tension on the repaired tendon due to shoulder motion. We hypothesized that botulinum toxin A injections would result in improved attachment strength and collagen organization at the tendon-bone interface at early time points but may result in decreased mechanical properties at later time points because of the negative effects of stress deprivation.nnnMATERIALS AND METHODSnWe performed division and repair of the supraspinatus tendon in 132 rats: 66 underwent repair alone and 66 received injections of botulinum toxin into the muscle before repair. Rats were killed at 4, 8, and 24 weeks and were evaluated by use of histologic, biomechanical, and micro-computed tomography analyses.nnnRESULTSnAt 4 and 24 weeks, there was no significant difference in load to failure between groups. At 8 weeks, the botulinum group had a significantly lower load to failure compared with controls (27.7 N vs 46.7 N, P < .01). The weight of the supraspinatus muscle was significantly decreased at 4 and 8 weeks in the botulinum group, but it recovered by 24 weeks. Micro-computed tomography analysis showed the botulinum group to have significantly less bone volume, total mineral content, and total mineral density at 8 weeks. Histologic analysis showed formation of a more normal tidemark and increased collagen fiber organization in the botulinum specimens at 4 weeks.nnnDISCUSSIONnBotulinum toxin A-treated specimens had increased collagen fiber organization at 4 weeks and decreased mechanical properties at later time points. The rapid healing of the rat rotator cuff likely makes it difficult to realize benefits from reduction in strain.

Assessment of vascularity of the femoral head using gadolinium (Gd-DTPA)-enhanced magnetic resonance imaging: A CADAVER STUDY

In spite of extensive accounts describing the blood supply to the femoral head, the prediction of avascular necrosis is elusive. Current opinion emphasises the contributions of the superior retinacular artery but may not explain the clinical outcome in many situations, including intramedullary nailing of the femur and resurfacing of the hip. We considered that significant additional contribution to the vascularity of the femoral head may exist. A total of 14 fresh-frozen hips were dissected and the medial circumflex femoral artery was cannulated in the femoral triangle. On the test side, this vessel was ligated, with the femoral head receiving its blood supply from the inferior vincular artery alone. Gadolinium contrast-enhanced MRI was then performed simultaneously on both control and test specimens. Polyurethane was injected, and gross dissection of the specimens was performed to confirm the extraosseous anatomy and the injection of contrast. The inferior vincular artery was found in every specimen and had a significant contribution to the vascularity of the femoral head. The head was divided into four quadrants: medial (0), superior (1), lateral (2) and inferior (3). In our study specimens the inferior vincular artery contributed a mean of 56% (25% to 90%) of blood flow in quadrant 0, 34% (14% to 80%) of quadrant 1, 37% (18% to 48%) of quadrant 2 and 68% (20% to 98%) in quadrant 3. Extensive intra-osseous anastomoses existed between the superior retinacular arteries, the inferior vincular artery and the subfoveal plexus.

Endosteal Strut Augment Reduces Complications Associated With Proximal Humeral Locking Plates

BackgroundLocking-plate technology has renewed interest in plate fixation for treating proximal humerus fractures. Complications associated with these devices, including loss of reduction, screw cutout, and intra-articular penetration, are frequent. Establishing a second column of support may reduce complications and improve clinical outcome scores.Questions/purposesWe asked whether addition of an endosteal cortical allograft strut, used as an augment to locking-plate fixation for displaced proximal humerus fractures, would reduce complications and improve clinical outcome scores.Patients and MethodsWe retrospectively reviewed the charts and radiographs of 38 patients treated by this method. All patients were evaluated with serial radiographs, as well as the Disabilities of the Arm, Shoulder, and Hand and Constant-Murley scores. There were seven two-part, 19 three-part, and 12 four-part fractures. The minimum followup was 49xa0weeks (average, 75xa0weeks; range, 49–155xa0weeks).ResultsNo patient had intra-articular screw penetration or cutout. No patient had complete osteonecrosis, but one had partial osteonecrosis. The reduction was lost in one patient. The mean Disabilities of the Arm, Shoulder, and Hand score was 15 (range, 0–66.4). The mean Constant-Murley score was 87 (range, 51–95).ConclusionsLow rates of complication and high clinical outcome scores can be achieved when treating complex proximal humerus fractures with locking-plate fixation and an endosteal strut augment.Level of EvidenceLevel IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Locked Plating of the Proximal Humerus Using an Endosteal Implant

Purpose: To report on the use of a supplemental medial endosteal implant to prevent varus collapse and screw cutout in proximal humerus fractures treated with a laterally placed locking plate. Methods: Twenty-seven patients meeting study inclusion criteria were included in the study. Follow-up averaged 63.1 weeks (minimum 37 weeks and maximum 120 weeks). All patients were either older than 70 years or had sustained a proximal humerus fracture with medial comminution. Using the anterolateral acromial approach, a proximal humeral locking plate augmented with a medial endosteal implant (fibular allograft in 23 patients and semitubular plate in 4 patients) was used for fixation. Intraoperative fluoroscopic images and the most recent follow-up radiographs were used to measure the head–shaft angle and loss of height between the implant and the articular surface. Results: Only 1 of 27 patients had significant loss of reduction with collapse of the fracture into varus (4.2 mm change). Ninety-six percent of patients maintained their original reduction with an average loss of height of 1.2 mm and an average change in shaft–head angle of 2.2 degrees. There were no implant failures or screw perforations of the articular surface and no radiographic or clinical evidence of AVN. Conclusions: Use of a medial endosteal implant as a supplement to a lateral locking plate is effective in maintaining operative reduction, preventing varus collapse, and implant failure in fractures with medial comminution and/or poor bone quality. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Rate of avascular necrosis following proximal humerus fractures treated with a lateral locking plate and endosteal implant

IntroductionTreatment of displaced proximal humerus fractures remains challenging. The introduction of locking plates has renewed interest in treating these fractures with joint-preserving techniques rather than hemiarthroplasty, but high complication rates are still reported. Avascular necrosis is not solely dependent on the initial fracture pattern, but can also result from intraoperative and postoperative vascular insults.MethodWe describe a technique to minimize disruption of humeral head blood supply and maximize fracture fixation. A total of 34 patients with complex proximal humerus fractures were treated with a locking plate and endosteal implant through an anterolateral approach and followed for an average of 66xa0weeks to determine the rates of avascular necrosis.ResultsNo patient suffered complete osteonecrosis (0%) and only one patient suffered partial necrosis (2.8%) of the humeral head. The length of the posteromedial hinge was not predictive of this complication.ConclusionUse of the anterolateral approach and endosteal augment of a lateral locking plate can minimize avascular necrosis following proximal humerus fracture.