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2. Subperiosteal delivery of transforming growth factor beta 1 and human growth hormone from mineralized PCL films.

Author

Parlato, Matthew B., Lee, Jae Sung, Belair, David G., Fontana, Gianluca, Leiferman, Ellen, Hanna, Rewais, Chamberlain, Connie, Ranheim, Erik A., Murphy, William L., and Halanski, Matthew A.

Abstract

The ability to locally deliver bioactive molecules to distinct regions of the skeleton may provide a novel means by which to improve fracture healing, treat neoplasms or infections, or modulate growth. In this study, we constructed single‐sided mineral‐coated poly‐ε‐caprolactone membranes capable of binding and releasing transforming growth factor beta 1 (TGF‐β1) and human growth hormone (hGH). After demonstrating biological activity in vitro and characterization of their release, these thin bioabsorbable membranes were surgically implanted using an immature rabbit model. Membranes were circumferentially wrapped under the periosteum, thus placed in direct contact with the proximal metaphysis to assess its bioactivity in vivo. The direct effects on the metaphyseal bone, bone marrow, and overlying periosteum were assessed using radiography and histology. Effects of membrane placement at the tibial growth plate were assessed via physeal heights, tibial growth rates (pulsed fluorochrome labeling), and tibial lengths. Subperiosteal placement of the mineralized membranes induced greater local chondrogenesis in the plain mineral and TGF‐β1 samples than the hGH. More exuberant and circumferential ossification was seen in the TGF‐β1 treated tibiae. The TGF‐β1 membranes also induced hypocellularity of the bone marrow with characteristics of gelatinous degeneration not seen in the other groups. While the proximal tibial growth plates were taller in the hGH treated than TGF‐β1, no differences in growth rates or overall tibial lengths were found. In conclusion, these data demonstrate the feasibility of using bioabsorbable mineral coated membranes to deliver biologically active compounds subperiosteally in a sustained fashion to affect cells at the insertion site, bone marrow, and even growth plate. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Best Practices for the Orthopaedic Care of Children with Spinal Muscular Atrophy: A Consensus Statement from the European Neuromuscular Centre Standard of Care Orthopaedic Working Group

Author

Vitale, Michael, Roye, Benjamin, Bloom, Zachary, Kunes, Jennifer A., Matsumoto, Hiroko, Roye, David, Farrington, David, Flynn, Jack, Halanski, Matthew, Hasler, Carol, Miladi, Lotfi, Quijano-Roy, Susana, Reilly, Christopher, Sponseller, Paul, Yazici, Muharrem, and Snyder, Brian

Published
2022
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7. The Physis: Fundamental Knowledge to a Fantastic Future Through Research: Proceedings of the AAOS/ORS Symposium

Author

Halanski, Matthew A., Wallace, Maegen J., Schipani, Ernestina, Kronenberg, Henry, Serra, Rosa, Nilsson, Ola, White, Klane, Bober, Michael, Alman, Benjamin, Hoernschemeyer, Daniel, De Luca, Francesco, Wit, Jan-Maarten, Noonan, Ken, Paloian, Neil, Deyle, David, Gilbert, Shawn, Sabharwal, Sanjeev, Stevens, Peter, Schoenecker, Jonathan, Larson, Noelle, Milbrandt, Todd, and Li, Wan-Ju

Published
2020
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15. Is prophylactic formal fusion with implant revision necessary in non-ambulatory children with spinal muscular atrophy and growing rods who are no longer lengthened?

Author

Hanna, Rewais, Sharafinski, Mark, Patterson, Karen, Noonan, Kenneth J., Sund, Sarah, Schultz, Meredith, Schroth, Mary K., Hetzel, Scott, and Halanski, Matthew A.

Abstract

Study design: Single center, retrospective chart review. Objectives: To determine if routine posterior spinal fusion (PSF) is unnecessary in non-ambulatory growing rod graduates with SMA. Summary of background data: Most non-ambulatory children with SMA develop early-onset scoliosis (EOS). Posterior growing rods (GR) have been shown safe and effective in managing spinal deformities in these children. The best management of these children, once graduated from their GR, is currently unknown. In this study, we report the clinical results of managing these children without routine definitive fusion following a course of GR treatment. Methods: A single-center, retrospective chart and radiographic review was performed on children with SMA treated with posterior distraction GR, with a two-year minimum follow-up since final lengthening. Electronic medical records and radiographs were reviewed for demographic variables, Cobb measurements, implant revisions, occult radiographic implant failure, symptomatic failure, and/or conversion to PSF. Result: 12 patients (2 type 1, 9 type 2, 1 type 1/2) met inclusion criteria. Mean age at growing rod insertion was 6.2 years of age (range 4.1–8.2) and age at final lengthening 10.3 years of age (range 9.3–11.9). The mean time between last lengthening and latest clinical or radiographic review was 5.5 (range 2.1–9.0) years. Average mean pre, post, final Cobb angles were 71°, 27° (p< 0.001), 25°. Following final lengthening, only one patient required hardware revision and conversion to definitive fusion in attempts to alleviate chronic hip pain, which was unsuccessful. One additional patient was found to have an occult rod failure that has not required treatment. Conclusion: While limited by sample size, this single-center cohort of non-ambulatory SMA patients with EOS treated with similar constructs suggests that routine, definitive fusion in SMA GR graduates may be unnecessary. Level of evidence: Level IV.

Published
2024
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17. Peri-operative management of children with spinal muscular atrophy

Author

Halanski, Matthew, Steinfeldt, Andrew, Hanna, Rewais, Hetzel, Scott, Schroth, Mary, and Muldowney, Bridget

Subjects
Spinal muscular atrophy, Orthopedic surgery, Nusinersen, Medical research, Remifentanil, Company business management, Health
Abstract

Byline: Matthew. Halanski, Andrew. Steinfeldt, Rewais. Hanna, Scott. Hetzel, Mary. Schroth, Bridget. Muldowney Background and Aims: Current multi-disciplinary management of children with spinal muscular atrophy (SMA) often requires the surgical [...]

Published
2020

40. KIAA1217: A novel candidate gene associated with isolated and syndromic vertebral malformations

Author

Al Dhaheri, Noura, primary, Wu, Nan, additional, Zhao, Sen, additional, Wu, Zhihong, additional, Blank, Robert D., additional, Zhang, Jianguo, additional, Raggio, Cathy, additional, Halanski, Matthew, additional, Shen, Jianxiong, additional, Noonan, Ken, additional, Qiu, Guixing, additional, Nemeth, Blaise, additional, Sund, Sarah, additional, Dunwoodie, Sally L., additional, Chapman, Gavin, additional, Glurich, Ingrid, additional, Steiner, Robert D., additional, Wohler, Elizabeth, additional, Martin, Renan, additional, Sobreira, Nara Lygia, additional, and Giampietro, Philip F., additional

Published
2020
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42. 2020

Author

Egeland, Marc A., primary, Vanderbilt, Timothy, additional, Hanna, Rewais, additional, Lufrano, Reuben, additional, Vanderby, Ray, additional, Goodspeed, Dave, additional, and Halanski, Matthew A., additional

Published
2020
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49. Exosome‐educated macrophages and exosomes differentially improve ligament healing.

Author

Chamberlain, Connie S., Kink, John A., Wildenauer, Linzie A., McCaughey, Maxwell, Henry, Katie, Spiker, Andrea M., Halanski, Matthew A., Hematti, Peiman, and Vanderby, Ray

Subjects
EXOSOMES, MACROPHAGES, COLLATERAL ligament, STROMAL cells, TISSUE remodeling
Abstract

Recently, our group used exosomes from mesenchymal stromal/stem cells (MSCs) to simulate an M2 macrophage phenotype, that is, exosome‐educated macrophages (EEMs). These EEMs, when delivered in vivo, accelerated healing in a mouse Achilles tendon injury model. For the current study, we first tested the ability of EEMs to reproduce the beneficial healing effects in a different rodent model, that is, a rat medial collateral ligament (MCL) injury model. We hypothesized that treatment with EEMs would reduce inflammation and accelerate ligament healing, similar to our previous tendon results. Second, because of the translational advantages of a cell‐free therapy, exosomes alone were also examined to promote MCL healing. We hypothesized that MSC‐derived exosomes could also alter ligament healing to reduce scar formation. Similar to our previous Achilles tendon results, EEMs improved mechanical properties in the healing ligament and reduced inflammation, as indicated via a decreased endogenous M1/M2 macrophage ratio. We also showed that exosomes improved ligament remodeling as indicated by changes in collagen production and organization, and reduced scar formation but without improved mechanical behavior in healing tissue. Overall, our findings suggest EEMs and MSC‐derived exosomes improve healing but via different mechanisms. EEMs and exosomes each have attractive characteristics as therapeutics. EEMs as a cell therapy are terminally differentiated and will not proliferate or differentiate. Alternatively, exosome therapy can be used as a cell free, shelf‐stable therapeutic to deliver biologically active components. Results herein further support using EEMs and/or exosomes to improve ligament healing by modulating inflammation and promoting more advantageous tissue remodeling. [ABSTRACT FROM AUTHOR]

Published
2021
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