Yaszemski, Michael J.

AbstractA critical component of many tissue‐engineered medical products (TEMPs) is the scaffold or biomaterial. The industry's understanding of scaffold properties and their influence on cell behavior has advanced, but our technical capability to reliably characterize scaffolds requires improvement, especially to enable large‐scale manufacturing. In response to the key findings from the 2013 ASTM International Workshop of Standards and Measurements for Tissue Engineering Scaffolds, the National Institute of Standards and Technology (NIST), ASTM International, BiofabUSA, and the Standards Coordinating Body (SCB) organized a workshop in 2018 titled, “Characterization of Fiber‐Based Scaffolds”. The goal was to convene a group of 40 key industry stakeholders to identify major roadblocks in measurements of fiber‐based scaffold properties. This report provides an overview of the findings from this collaborative workshop. The four major consensus findings were that (a) there is need for a documentary standard guide that would aid developers in the selection of test methods for characterizing fiber‐based scaffolds; (b) there is a need for a strategy to assess the quality of porosity and pore size measurements, which could potentially be ameliorated by the development of a reference material; (b) there are challenges with the lexicon used to describe and assess scaffolds; and (d) the vast array of product applications makes it challenging to identify consensus test methods. As a result of these findings, a working group was formed to develop an ASTM Standard Guide for Characterizing Fiber‐Based Constructs that will provide developers guidance on selecting measurements for characterizing fiber‐based scaffolds.

AbstractBackgroundLocal recurrence (LR) of sacral chordoma is a difficult problem and the mortality risk associated with LR remains poorly described. The purpose of this study was to evaluate the risk of mortality in patients with LR and determine if patient age is associated with mortality.MethodsA total of 218 patients (144 male, 69 female; mean age 59 ± 15 years) with sacrococcygeal chordomas were reviewed. Cumulative incidence functions and competing risks for death due to disease and nondisease mortality were employed to analyze mortality trends following LR.ResultsThe 10‐year overall survival (OS) was 55%. Patients with LR had 44% 10‐year OS, similar to patients without (59%; P = .38). The 10‐year OS between those less than 55 compared with ≥55 years were similar (69% vs 48%; P = .52). The 10‐year death due to disease was worse in patients with LR compared with those without (44% vs 84%; P < .001). In patients without LR, patients ≥55 years were 1.6‐fold more likely to experience death due to other causes.ConclusionsPatients with an LR are more likely to die due to disease. Advanced patient age was associated with higher all‐cause mortality following resection of sacral chordoma. LR of chordoma was associated with increased disease‐specific mortality, regardless of age.

ABSTRACTNeither allograft nor commercially available bone graft substitutes provide the same quality of bone healing as autograft. Incorporation of bioactive molecules like parathyroid hormone (PTH) within bone graft substitute materials may provide similar, if not better treatment options to grafting. The goal of this work was to develop a biomaterial system for the local delivery of PTH to large bone defects for promoting bone regeneration. PTH was loaded in a thiol‐ene hydrogel at several concentrations and polymerized in and around an osteoconductive poly(propylene fumarate) (PPF) scaffold. PTH was shown to be bioactive when released from the hydrogel for up to 21 days. Eighty percent of the PTH was released by day 3 with the remaining 20% released by day 14. Bone healing was quantified in rat critical size femoral defects that were treated with hydrogel/PPF and 0, 1, 3, 10, or 30 µg of PTH. Although complete osseous healing was not observed in all samples in any one treatment group, all samples in the 10 µg PTH group were bridged fully by bone or a combination of bone and cartilage containing hypertrophic chondrocytes and endochondral ossification. Outcome measures indicated improved defect bridging by a combination of bony and cartilaginous tissue in the 10 μg treatment group compared with empty bone defects and defects treated with only hydrogel/PPF (i.e., without PTH). Given the tailorability of the hydrogel, future studies will investigate the effects of prolonged gradual PTH release on bone healing. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:536–544, 2020

OBJECTIVEThe authors sought to assess whether Hounsfield units (HU) increase following teriparatide treatment and to compare HU increases with changes in bone mineral density (BMD) as measured by dual-energy x-ray absorptiometry (DEXA).METHODSA retrospective chart review was performed from 1997 to 2018 across all campuses at our institution. The authors identified patients who had been treated with at least 6 months of teriparatide and compared HU and BMD as measured on DEXA scans before and after treatment.RESULTSFifty-two patients were identified for analysis (46 women and 6 men, average age 67 years) who underwent an average of 20.9 ± 6.5 months of teriparatide therapy. The mean ± standard deviation HU increase throughout the lumbar spine (L1–4) was from 109.8 ± 53 to 133.9 ± 61 HU (+22%, 95% CI 1.2–46, p value = 0.039). Based on DEXA results, lumbar spine BMD increased from 0.85 to 0.93 g/cm2 (+9%, p value = 0.044). Lumbar spine T-scores improved from −2.4 ± 1.5 to −1.7 ± 1.5 (p value = 0.03). Average femoral neck T-scores improved from −2.5 ± 1.1 to −2.3 ± 1.0 (p value = 0.31).CONCLUSIONSTeriparatide treatment increased both HU and BMD on DEXA in the lumbar spine, without a change in femoral BMD. The 22% improvement in HU surpassed the 9% improvement determined with DEXA. These results support some surgeons’ subjective sense that intraoperative bone quality following teriparatide treatment is better than indicated by DEXA results. To the authors’ knowledge, this is the first study demonstrating an increase in HU with teriparatide treatment.

Study Design: A retrospective study. Objectives: (1) To assess the reliability of using the posterior endplate valley (PEV) to predict the cranial-caudal location of the cervical pedicle intraoperatively; (2) to assess the impact of age on the cervical PEV-pedicle relationship, interpedicular distance, and foraminal height. Summary of Background Data: The cervical pedicle, which is the anatomic landmark defining the boundaries of the foramen, is hidden from view intraoperatively in the anterior cervical approach, potentially leading to incomplete foraminal decompression. An intraoperative landmark which heralds the location of the pedicle and therefore can be relied upon as a guide for decompression has not been previously described. Methods: We retrospectively reviewed cervical computed tomography images of younger (<50 y) and older (>50 y) patients. Using the coronal reconstructed image taken at the posterior margin of the vertebral body, we constructed a line between the superior aspect of the pedicles and measured the distance from this line to the PEV. Interpedicular distance and foraminal height were also measured. Results: One hundred patients were included in the final analysis. The mean distance (mm) from the pedicular line to the PEV from C3 to C7 respectively was 1.0±0.99, 0.01±0.76, 0.09±0.70, 0.20±0.71, and 0.27±0.79. No significant difference between young and elderly patients was noted (P<0.05). Intervertebral foraminal size was significantly greater in younger compared with elderly patients at all levels except C2–C3. The mean interpedicular distance was 23.05±1.76 mm. Conclusions: This study demonstrates, for the first time, that the PEV is an accurate surgical landmark that is consistently at most 1 mm from the superior aspect of the cervical pedicle in the subaxial spine. Furthermore, this study demonstrated that foraminal height was significantly larger in younger compared with elderly patients at all cervical levels below C3. Level of Evidence: Level 3.

AbstractBackgroundWe reviewed the disease control and complications of the treatment of sacrococcygeal chordoma from four tertiary cancer centers with emphasis on the effects of radiotherapy in surgically treated patients.MethodsA total of 193 patients with primary sacrococcygeal chordoma from 1990 to 2015 were reviewed. There were 124 males, with a mean age of 59 ± 15 years and a mean follow‐up of 7 ± 4 years. Eighty‐nine patients received radiotherapy with a mean total dose of 61.8 ± 10.9 Gy.ResultsThe 10‐year disease‐free and disease‐specific survival was 58% and 72%, respectively. Radiation was not associated with local recurrence (hazard ratio [HR], 1.13; 95% confidence interval [CI], 0.59‐2.17; P = 0.71), metastases (HR, 0.93; 95% CI, 0.45‐1.91; P = 0.85) or disease‐specific survival (HR, 0.96; 95% CI, 0.46‐2.00; P = 0.91). Higher doses (≥70 Gy; HR, 0.52; 95% CI, 0.20‐1.32; P = 0.17) may be associated with reduced local recurrence. Radiotherapy was associated with wound complications (HR, 2.76; 95% CI, 1.64‐4.82;, P < 0.001) and sacral stress fractures (HR, 4.73; 95% CI, 1.88‐14.38; P < 0.001).ConclusionsIn this multicenter review, radiotherapy was not associated with tumor outcome but associated with complications. The routine use of radiotherapy with en‐bloc resection of sacrococcygeal chordomas should be reconsidered in favor of a selective, individualized approach with a radiation dose of ≥70 Gy.

Biomaterials that act as both protein delivery vehicle and scaffold can improve the safety and efficacy of bone morphogenetic protein-2 (BMP-2) for clinical applications. However, the optimal scaffold characteristics are not known. The osteoinductive and osteoconductive capacity of a fixed electrically charged surface is thus far unexplored. Therefore, in this study, we aim to investigate the effect of different electrical states on BMP-2-induced bone formation in oligo[(polyethylene glycol) fumarate] (OPF) hydrogels. Neutral, negatively, or positively charged scaffolds were fabricated using unmodified OPF (neutral charge), sodium methacrylate crosslinked OPF (negative charge), or [2-(methacryloyloxy) ethyl] trimethylammonium chloride crosslinked OPF (positive charge), respectively. To allow investigation of surface charge for different BMP-2 release rates, three BMP-2 release profiles were generated by protein encapsulation into poly(lactic-co-glycolic acid) microspheres and/or adsorption on the OPF composite. Release of radiolabeled 125 I-BMP-2 was analyzed in vitro and in vivo and bone formation was assessed after 9 weeks of subcutaneous implantation in rats. Negatively charged OPF generated significantly more bone formation compared with neutral and positively charged OPF. This effect was seen for all three loading methods and subsequent BMP-2 release profiles. Along with charge modifications, a more sustained release of BMP-2 improved overall bone formation in OPF composites. Overall, this study clearly shows that negative charge enhances bone formation compared with neutral and positive charge in OPF composites. Impact Statement Biomaterials can play a dual role in bone regeneration: they enable local sustained delivery of growth factors, such as bone morphogenetic protein-2 (BMP-2), while they provide structural support as scaffold. By better imitating the properties of native bone tissue, scaffolds may be both osteoconductive and osteoinductive. The latter can be achieved by modifying the electrical charge of the surface. The present work uses tunable oligo[(polyethylene glycol) fumarate] hydrogel and demonstrates that negative charge enhances BMP-2-induced bone formation compared with neutral or positive charge. Altogether, this indicates that tissue-specific surface charge modifications of biomaterials hold great promise in the field of tissue regeneration.

Study Design: This is a prospective cohort study. Objective: To characterize the accuracy of patient recollection of preoperative symptoms after cervical spine surgery. Summary of Background Data: Recall bias is a well-known source of systematic error. The accuracy of patient recall after cervical spine surgery remains unknown. Methods: Consecutive patients undergoing cervical spine surgery for myelopathy or radiculopathy were enrolled. Neck and arm numeric pain scores and Neck Disability Indices were recorded preoperatively. Patients were asked to recall their preoperative status at either short (<1 y) or long-term (≥1 y) follow-up. Actual and recalled scores were compared using paired t tests and relations were quantified using the Pearson correlation coefficients. Multivariable linear regression was used to identify factors impacting recollection. Results: In total, 73 patients with a mean age of 58.2 years were included. Compared with their preoperative scores, patients showed significant improvement in neck pain [mean difference (MD)=−2.9; 95% confidence intervals (CIs), −3.5 to −2.3], arm pain (MD, −3.4; 95% CI, −4.0 to −2.8), and disability (MD, −12.4%; 95% CI, −16.9 to −7.9). Patient recollection of preoperative status was significantly more severe than actual for neck pain (MD, +1.5; 95% CI, 0.8–2.2), arm pain (MD, +2.3; 95% CI, 1.6–3.0), and disability (MD, +5.8%; 95% CI, 2.4–9.2). Moderate correlation between actual and recalled scores with regard to neck (r=0.41), arm (r=0.50) pain, and disability (r=0.67) was seen. This was maintained across age, sex, and time between date of surgery and recollection. Over 30% of patients switched their predominant symptom from neck-to-arm pain or vice versa on recall of their preoperative symptoms. Conclusions: Relying on patient recollection does not provide an accurate measure of preoperative status after cervical spine surgery. Prospective and not retrospective collection of patient-reported outcomes remain the gold standard to measure and interpret outcomes after cervical spine surgery. Recall bias has the potential to affect patient satisfaction and requires further study.