Yaszemski, Michael J.

Abstract Purpose: Pathologic fractures could be prevented if reliable methods of fracture risk assessment were available. A multicenter prospective study was conducted to identify significant predictors of physicians' treatment plan for skeletal metastasis based on clinical fracture risk assessments and the proposed CT-based Rigidity Analysis (CTRA). Experimental Design: Orthopedic oncologists selected a treatment plan for 124 patients with 149 metastatic lesions based on the Mirels method. Then, CTRA was performed, and the results were provided to the physicians, who were asked to reassess their treatment plan. The pre- and post-CTRA treatment plans were compared to identify cases in which the treatment plan was changed based on the CTRA report. Patients were followed for a 4-month period to establish the incidence of pathologic fractures. Results: Pain, lesion type, and lesion size were significant predictors of the pre-CTRA plan. After providing the CTRA results, physicians changed their plan for 36 patients. CTRA results, pain, and primary source of metastasis were significant predictors of the post-CTRA plan. Follow-up of patients who did not undergo fixation resulted in 7 fractures; CTRA predicted these fractures with 100% sensitivity and 90% specificity, whereas the Mirels method was 71% sensitive and 50% specific. Conclusions: Lesion type and size and pain level influenced the physicians' plans for the management of metastatic lesions. Physicians' treatment plans and fracture risk predictions were significantly influenced by the availability of CTRA results. Due to its high sensitivity and specificity, CTRA could potentially be used as a screening method for pathologic fractures. Clin Cancer Res; 21(11); 2514–9. ©2015 AACR.

Three-dimensional polymer scaffolds with interconnected porous structures were fabricated by thermally induced phase separation of novel biodegradable poly(propylene fumarate)- co -poly( l -lactic acid).

AbstractIn tissue engineering, development of an osteoconductive construct that integrates with host tissue remains a challenge. In this work, the effect of bone‐like minerals on maturation of pre‐osteoblast cells was investigated using polymer‐mineral scaffolds composed of poly(propylene fumarate)‐co‐poly(caprolactone) (PPF‐co‐PCL) and nano‐sized hydroxyapatite (HA). The HA of varying concentrations was added to an injectable formulation of PPF‐co‐PCL and the change in thermal and mechanical properties of the scaffolds was evaluated. No change in onset of degradation temperature was observed due to the addition of HA, however compressive and tensile moduli of copolymer changed significantly when HA amounts were increased in composite formulation. The change in mechanical properties of copolymer was found to correlate well to HA concentration in the constructs. Electron microscopy revealed mineral nucleation and a change in surface morphology and the presence of calcium and phosphate on surfaces was confirmed using energy dispersive X‐ray analysis. To characterize the effect of mineral on attachment and maturation of pre‐osteoblasts, W20‐17 cells were seeded on HA/copolymer composites. We demonstrated that cells attached more to the surface of HA containing copolymers and their proliferation rate was significantly increased. Thus, these findings suggest that HA/PPF‐co‐PCL composite scaffolds are capable of inducing maturation of pre‐osteoblasts and have the potential for use as scaffold in bone tissue engineering. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 2549–2557, 2015.

AbstractThe “Workshop on Standards & Measurements for Tissue Engineering Scaffolds” was held on May 21, 2013 in Indianapolis, IN, and was sponsored by the ASTM International (ASTM). The purpose of the workshop was to identify the highest priority items for future standards work for scaffolds used in the development and manufacture of tissue engineered medical products (TEMPs). Eighteen speakers and 78 attendees met to assess current scaffold standards and to prioritize needs for future standards. A key finding was that the ASTM TEMPs subcommittees (F04.41‐46) have many active “guide” documents for educational purposes, but few standard “test methods” or “practices.” Overwhelmingly, the most clearly identified need was standards for measuring the structure of scaffolds, followed by standards for biological characterization, including in vitro testing, animal models and cell‐material interactions. The third most pressing need was to develop standards for assessing the mechanical properties of scaffolds. Additional needs included standards for assessing scaffold degradation, clinical outcomes with scaffolds, effects of sterilization on scaffolds, scaffold composition, and drug release from scaffolds. Discussions highlighted the need for additional scaffold reference materials and the need to use them for measurement traceability. Workshop participants emphasized the need to promote the use of standards in scaffold fabrication, characterization, and commercialization. Finally, participants noted that standards would be more broadly accepted if their impact in the TEMPs community could be quantified. Many scaffold standard needs have been identified and focus is turning to generating these standards to support the use of scaffolds in TEMPs. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 949–959, 2015.

This is a technical note of pelvic reconstruction performed by an advanced multidisciplinary team. The authors report a new 3-stage reconstruction of the hemipelvis after Type 3 sacrectomy involving instrumented spinoiliac arthrodesis and pedicled fibula grafting in 2 patients. The anterior stage of the procedure begins with a transabdominal approach to mobilize the viscera and to free up the tumor from the vessels. The posterior divisions of internal iliac vessels, the middle sacral vessels, and the lateral sacral vessels are then ligated. An anterior vertebrectomy is done at the appropriate level, followed by an anterior osteotomy through the lateral planed surgical margin of the sacrum close to the salvaged sacroiliac joint. The second stage includes a major sacral resection with lower-extremity amputation from the pubic symphysis through the intact side of the sacrum, ipsilateral pedicled fibula harvesting, and closure with an ipsilateral pedicled quadriceps flap. The final stage involves reconstruction with lumboiliac instrumentation. The pedicled fibular graft left from the second stage is then placed distally within the previously created iliopectineal docking site and proximally within the L-5 docking site. The authors believe that this is a feasible and reproducible technique with theoretical advantages that have to be proved in the long-term follow-up.

ABSTRACTIntroduction: Isometric muscle force measurement is a sensitive marker for motor function recovery in rat nerve repair models. Current methods of eliciting maximal isometric force with nerve stimulation cannot provide longitudinal data.Methods: We developed a novel method for measuring isometric muscle force with a device designed to allow minimally invasive nerve stimulation and measurement of plantar flexion force. This indirectly elicited muscle force was compared with muscle force elicited by direct muscle stimulation in 3 surgical models.Results: The force measured after sciatic nerve transection and repair followed a parabolic trend. There was a postinjury decrease in force that continued until postoperative day 42, after which the force increased with time, indicating muscle reinnervation.Conclusions: This approach can track longitudinal changes in force in the most common animal model for studies of clinically relevant problems in the peripheral nerve field.Muscle Nerve50: 812–821, 2014

Osteosarcoma is a bone tumor that affects children and young adults. 2‐Methoxyestradiol (2‐ME), a naturally occurring estrogen metabolite, kills osteosarcoma cells, but does not affect normal osteoblasts. In order to effectively target osteosarcoma and improve the therapeutic index of the drug 2‐ME, we have encapsulated 2‐ME in a composite of oligo‐(polyethylene glycol) fumarate (OPF) hydrogel and poly (lactic‐co‐glycolic acid) (PLGA) microspheres and investigated the effect of polymer composition on 2‐ME release kinetics and osteosarcoma cell survival. The in vitro study shows that 2‐ME can be released in a controlled manner over 21‐days. The initial burst releases observed on day 1 were 50% and 32% for OPF and OPF/PLGA composites, respectively. The extended release kinetics show that 100% of the encapsulated 2‐ME is released by day 12 from OPF, whereas the OPF/PLGA composites showed a release of 85% on day 21. 2‐ME released from the polymers was biologically active and blocked osteosarcoma cell proliferation in vitro. Also, comparison of 2‐ME delivery in osteosarcoma cells in culture, shows that direct treatment has no effect after 3 days, whereas polymer‐mediated delivery produces anti‐tumor effects that could be sustained for 21 days. These findings show that the OPF and PLGA polymeric system may prove to be useful in controlled and sustained delivery of 2‐ME and could be further explored in the treatment of osteosarcoma. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 2491–2499, 2013.