Osteoporosis represents a major health problem in terms of compromising bone strength and increasing the risk of bone fractures. It can be medically treated with bisphosphonates, which act systemically upon oral or venous administration. Further, bone regenerative treatments in osteoporotic conditions present a challenge. Here, we focused on the development of a synthetic bone substitute material with local diminishing effects on osteoporosis. Composites were created using calcium phosphate cement (CPC; 60 wt%) and polylactic-co-glycolic acid (PLGA; 40 wt%), which were loaded with alendronate (ALN). In vitro results showed that ALN-loaded CPC/PLGA composites presented clinically suitable properties, including setting times, appropriate compressive strength, and controlled release of ALN, the latter being dependent on composite degradation. Using a rat femoral condyle bone defect model in osteoporotic animals, ALN-loaded CPC/PLGA composites demonstrated stimulatory effects on bone formation both within and outside the defect region.

Abstract:The current study aimed to evaluate the biological performance of calcium phosphate cement (CPC) with polylactic-co-glycolic acid (PLGA) micro-particles and Bio-Oss V R in ovariectomized and healthy rats. Thirty-two Wistar rats received alternating experimental CPC/PLGA and Bio-Oss V R in femoral condyle defects in both femurs 6 weeks after ovariectomy (OVX, n 5 16) or sham operation (SHAM, n 5 16). Six weeks after OVX or SHAM surgery, bone morphology was analyzed by in vivo computed tomography (CT) to confirm osteoporotic bone condition. Analysis of bone formation and material remnants at 4 and 12 weeks after material implantation was performed by micro-CT, descriptive histology, histomorphometry and bone dynamics by fluorochrome labeling. The in vivo CT scans showed effective induction of osteoporotic bone condition by ovariectomy. Our data showed CPC/ PLGA degraded relatively faster and more steadily. However, Bio-Oss V R had significantly less material remnants and showed significantly more bone formation compared to CPC/ PLGA. Overall, our data showed relatively high amounts of CPC/PLGA for each time point, hampering new bone formation within the defect area. Osteoporotic conditions proved to significantly affect degradation rates, but did not significantly influence bone formation. An osteoporotic bone condition affects degradation of CPC/PLGA, which is vital information for its potential use in osteoporotic conditions.

IntroductionThe optimal surgical approach for trigger finger release remains controversial in hindsight of postoperative rehabilitation as well as scar tissue formation. In this study, we comparatively evaluated the outcome of three different types of skin incision by employing the “Disability of the Arm Shoulder and Hand Score” (DASH) and by quantitative ultrasound measurements of scar tissue volume.Materials and methodsThirty patients (32 triggerfingers) were enrolled in this study and randomly assigned to one of three groups: incision placed (1) transversal in distal palmar crease, (2) transversal and 2 mm distal from distal palmar crease, (3) longitudinally over MCP joint without crossing the distal palmar crease. Patients characteristics were noted and DASH scores were retrieved at four time points, (1) preoperatively (baseline), (2) 1 month, (3) 3 months, (4) 12 months postoperatively. Scar volume formation was assessed by ultrasound at 3 months postoperatively in 28 patients.ResultsAll groups showed a significant reduction in DASH values at 3 and 12 months postoperatively when compared to their own baseline levels. Group 3 showed the fastest and most pronounced reduction in DASH values at 1 month. Scar tissue formation was almost 57 % increased in group 1 vs group 2 and 3, however, not significant.ConclusionThere is no clear benefit of one incision technique over another. However, based on scar volume parameters, the significant faster recovery in the first month and the surgical ease of exposure and wound closure inclines us to favor the longitudinal incision (group 3) in future patients.

Biosilicate(®) and Bio-Oss(®) are two commercially available bone substitutes, however, little is known regarding their efficacy in osteoporotic conditions. The purpose of this study was to evaluate the osteogenic properties of both materials, at tissue and molecular level. Thirty-six Wistar rats were submitted to ovariectomy (OVX) for inducing osteoporotic conditions and sham surgery (SHAM) as a control. Bone defects were created in both femurs, which were filled with Biosilicate(®) or Bio-Oss(®), and empty defects were used as control. For the healthy condition both Biosilicate(®) and Bio-Oss(®) did not improve bone formation after 4 weeks. Histomorphometric evaluation of osteoporotic bone defects with bone substitutes showed more bone formation, significant for Bio-Oss(®). Molecular biological evaluation was performed by gene-expression analysis (Runx-2, ALP, OC, OPG, RANKL). The relative gene expression was increased with Biosilicate(®) for all genes in OVX rats and for Runx-2, ALP, OC and RANKL in SHAM rats. In contrast, with Bio-Oss(®), the relative gene expression of OVX rats was similar for all three groups. For SHAM rats it was increased for Runx-2, ALP, OC and RANKL. Since both materials improved bone regeneration in osteoporotic conditions, our results suggest that bone defects in osteoporotic conditions can be efficiently treated with these two bone substitutes.

The aim of the current study is to assess the biological performance of self‐healing hydrogels based on calcium phosphate (CaP) nanoparticles and bisphosphonate (BP) conjugated hyaluronan (HA) in a critical size segmental femoral bone defect model in rats. Additionally, these hydrogels are loaded with bone morphogenetic protein 2 (BMP‐2) and their performance is compared in healthy and osteoporotic bone conditions. Treatment groups comprise internal plate fixation and placement of a PTFE tube containing hydrogel (HABP‐CaP) or hydrogel loaded with BMP‐2 in two dosages (HABP‐CaP‐lowBMP2 or HABP‐CaP‐highBMP2). Twelve weeks after bone defect surgery, bone formation is analyzed by X‐ray examination, micro‐CT analysis, and histomorphometry. The data show that critical size, segmental femoral bone defects cannot be healed with HABP‐CaP gel alone. Loading of the HABP‐CaP gel with low dose BMP‐2 significantly improve bone formation and resulted in defect bridging in 100% of the defects. Alternatively, high dose BMP‐2 loading of the HABP‐CaP gel does not improve bone formation within the defect area, but leads to excessive bone formation outside the defect area. Bone defect healing is not affected by osteoporotic bone conditions.

This work aimed to compare in vitro degradation of dense PLGA microspheres and milled PLGA particles as porogens within CPC, considering that the manufacturing of milled PLGA is more cost-effective when compared with PLGA microspheres. Additionally, we aimed to examine the effect of porogen amount within CPC/PLGA on degradation and bone formation. Our in vitro results showed no differences between both forms of PLGA particles (as porogens in CPC; spherical for microspheres, irregular for milled) regarding morphology, porosity, and degradation. Using milled PLGA as porogens within CPC/PLGA, we evaluated the effect of porogen amount on degradation and bone forming capacity in vivo. Titanium landmarks surrounded by CPC/PLGA with 30 and 50 wt % PLGA, were implanted in forty femoral bone defects of twenty male Wistar rats. Histomorphometrical results showed a significant temporal decrease in the amount of CPC, for both formulas, and confirmed that 50 wt % PLGA degrades faster than 30 wt%, and allows for a 1.5-fold higher amount of newly formed bone. Taken together, this study demonstrated that (i) milled PLGA particles perform equal to PLGA microspheres, and (ii) tuning of the PLGA content in CPC/PLGA is a feasible approach to leverage material degradation and bone formation.

Demineralized bone matrix (DBM) is an allograft bone substitute used for bone repair surgery to overcome drawbacks of autologous bone grafting, such as limited supply and donor-site comorbidities. In view of different demineralization treatments to obtain DBM, we examined the biological performance of two differently demineralized types of DBM, i.e. by acidic treatment using hydrochloric acid (HCl) or treatment with the chelating agent ethylene diamine tetra-acetate (EDTA). First, we evaluated the osteo-inductive properties of both DBMs by implanting the materials subcutaneously in rats. Second, we evaluated the effects on bone formation by incorporating DBM in a hyaluronic acid (HA) gel to fill a porous titanium scaffold for use in a critical-sized calvarial defect model in 36 male Wistar rats. These porous titanium scaffolds were implanted empty or filled with HA gel containing either DBM HCl or DBM EDTA. Ectopically implanted DBM HCl and DBM EDTA did not induce ectopic bone formation over the course of 12 weeks. For the calvarial defects, mean percentages of newly formed bone at 2 weeks were significantly higher for Ti-Empty compared to Ti-HA + DBM HCl but not compared to Ti-HA + DBM EDTA. Significant temporal bone formation was observed for Ti-Empty and Ti-HA + DBM HCl, but not for Ti-HA + DBM EDTA. At 8 weeks there were no significant differences in values of bone formation between the three experimental constructs. In conclusion, these results showed that, under the current experimental conditions, neither DBM HCl nor DBM EDTA possess osteo-inductive properties. Additionally, in combination with an HA gel loaded in a porous titanium scaffold, DBM HCl and DBM EDTA showed similar amounts of new bone formation after 8 weeks, which were lower than using the empty porous titanium scaffold. Copyright © 2016 John Wiley & Sons, Ltd.