Spatial control of bone formation using a porous polymer scaffold co-delivering anabolic RHBMP-2 and anti-resorptive agents

Current clinical delivery of recombinant human bone morphogenetic proteins (rhBMPs) utilises freeze-dried collagen. Despite effective new bone generation, rhBMP via collagen can be limited by significant complications due to inflammation and uncontrolled bone formation. This study aimed to produce an alternative rhBMP local delivery system to permit more controllable and superior rhBMP-induced bone formation. Cylindrical porous poly(lactic-co-glycolic acid) (PLGA) scaffolds were manufactured by thermally-induced phase separation. Scaffolds were encapsulated with anabolic rhBMP-2 (20 μg) ± anti-resorptive agents: zoledronic acid (5 μg ZA), ZA pre-adsorbed onto hydroxyapatite microparticles, (5 μg ZA/2 % HA) or IkappaB kinase (IKK) inhibitor (10 μg PS-1145). Scaffolds were inserted in a 6-mm critical-sized femoral defect in Wistar rats, and compared against rhBMP-2 via collagen. The regenerate region was examined at 6 weeks by 3D microCT and descriptive histology. MicroCT and histology revealed rhBMP-induced bone was more restricted in the PLGA scaffolds than collagen scaffolds (-92.3 % TV, p < 0.01). The regenerate formed by PLGA + rhBMP-2/ZA/HA showed comparable bone volume to rhBMP-2 via collagen, and bone mineral density was +9.1 % higher (p < 0.01). Local adjunct ZA/HA or PS-1145 significantly enhanced PLGA + rhBMP-induced bone formation by +78.2 % and +52.0 %, respectively (p ≤ 0.01). Mechanistically, MG-63 human osteoblast-like cells showed cellular invasion and proliferation within PLGA scaffolds. In conclusion, PLGA scaffolds enabled superior spatial control of rhBMP-induced bone formation over clinically-used collagen. The PLGA scaffold has the potential to avoid uncontrollable bone formation-related safety issues and to customise bone shape by scaffold design. Moreover, local treatment with anti-resorptive agents incorporated within the scaffold further augmented rhBMP-induced bone formation

Delamination Cysts: A Predictor of Acetabular Cartilage Delamination in Hips with a Labral Tear

The treatment and prognosis of labral tears of the hip depend primarily on whether there is concomitant injury of the adjacent acetabular articular cartilage. We asked whether a delamination cyst on the preoperative plain radiographs correlated with delamination of the acetabular articular cartilage at the time of hip arthroscopy. We reviewed the preoperative radiographs of 125 consecutive hips that had a labral tear at hip arthroscopy for the presence of a delamination cyst. A delamination cyst was defined as an acetabular subchondral cyst either directly adjacent to a lateral acetabular cyst or in relation to a subchondral crack in the anterosuperior portion of the acetabulum. All patients with acetabular cartilage delamination at arthroscopy were identified. There were 16 patients with delamination cysts on radiographs and 15 patients with cartilage delamination at arthroscopy. A delamination cyst on the preoperative anteroposterior and/or frog lateral radiographs of the hip accurately predicted acetabular cartilage delamination, especially in hips with labral tears not caused by a major trauma. A delamination cyst is a previously unrecognized and novel radiographic sign that can preoperatively identify acetabular cartilage delamination in patients with labral tears, thereby facilitating the selection of the appropriate surgery and determining prognosis

Symphysis Pubis Osteomyelitis with Bilateral Adductor Muscles Abscess

Osteomyelitis of the pubis symphysis is a rare condition. There have been various reports in the literature of inflammation and osteomyelitis as well as septic arthritis of pubic symphysis. However, due to the fact that these conditions are rare and that the usual presenting symptoms are very nonspecific, osteomyelitis of the pubic symphysis is often misdiagnosed, thus delaying definitive treatment. We present a case that to our knowledge is the first case in literature of osteomyelitis of the pubic symphysis in a 17-year-old boy with juvenile idiopathic arthritis (JIA), which was initially misdiagnosed and progressed to bilateral adductor abscesses. A high suspicion of such condition should be considered in a JIA patient who presents with symphysis or thigh pain

Radiographic Outcomes of a Percutaneous, Reproducible Distal Metatarsal Osteotomy for Mild and Moderate Bunions: A Multicenter Study.

Hallux valgus is a prevalent condition. Many open surgical methods of correction have been described. We performed a percutaneous, extra-articular distal metatarsal osteotomy for mild to moderate bunion deformity. The minimally invasive technique was used in 217 feet (180 patients; age 49 ± 4.7 years, mean ± standard deviation) at 4 centers in North America (Center 1: November 2012 to March 2017; Center 2: January 2010 to May 2016; Center 3: October 2013 to June 2016; Center 4: January 2015 to June 2017). The procedure was used in simultaneous bilateral cases in 28 patients (15.6%) and in nonsimultaneous bilateral cases in 9 patients (5.0%). Immediate postoperative weightbearing was used in all cases. The mean preoperative intermetatarsal angle, hallux abductus angle, and tibial sesamoid position were 14.6° ± 3.5°, 30.7° ± 7.8°, and 5.4 ± 1.4, respectively. At final follow-up of 9.3 ± 6.1 months, the mean intermetatarsal angle, hallux abductus angle, and tibial sesamoid position were 4.7° ± 2.8°, 8.4° ± 6.1°, and 2.0 ± 1.0, respectively (p \u3c .0001 for all comparisons). No major complications were noted. All 217 osteotomies achieved union; 3 feet (1.4%) in 3 patients (1.7%) experienced asymptomatic malunion. Superficial pin-site infection was seen in 42 (19.4%) of the 217 feet (39 patients, 21.7%). The radiographic results of this percutaneous technique appear to be reproducible across multiple centers, and the technique is useful when correcting intermetatarsal and hallux abductus angles. This percutaneous osteotomy for realignment of the first ray allows immediate postoperative weightbearing and, in this initial review, appears to be safe and effective, even in simultaneous bilateral cases

Biomechanical testing results.

<p>Biomechanical testing parameters to compare HS-injected bones and saline-injected (control) bones at 34 days and 51 days post-osteotomy. For statistical analysis, a two-tailed un-paired t test was performed between the HS-injected group and controls, in which * indicates p<0.05.</p

Classification of Bone Fill Scores.

<p>Classification of Bone Fill Scores.</p

Frequency of post-operative complications.

<p>The frequency of infection and early euthanasia was increased in the HS-injected group compared to controls. For statistical analysis, a two-tailed un-paired t test was performed between the HS-injected group and controls, in which * indicates p<0.05.</p

Summarized results for Immunohistochemistry analysis.

<p>Immunohistochemistry results of dissected tibiae at 34 days and 51 days post-osteotomy.</p

Microcomputed tomography (μCT) results.

<p>μCT histomorphometric analysis of distracted bone injected with 5 µg HS or saline (Control), at 34 and 51 days post-osteotomy. For statistical analysis, a two-tailed un-paired t test was performed between the HS-injected group and controls, in which * indicates p<0.05.</p

Average bone fill scores.

<p>Data is represented as a mean of Bone-fill scores, as blindly graded by radiological assessment.</p