Clinical Orthopaedics and Related Research ®

A Publication of The Association of Bone and Joint Surgeons ®

Basic Research 171 articles

Articles

Osteoblasts Have a Neural Origin in Heterotopic Ossification

ZaWaunyka W. Lazard BS, Elizabeth A. Olmsted-Davis PhD, Elizabeth A. Salisbury PhD, Zbigniew Gugala MD, PhD, Corrine Sonnet PhD, Eleanor L. Davis, Eric Beal BS, Eroboghene E. Ubogu MD, Alan R. Davis PhD

Heterotopic ossification (HO) is the process of bone formation at a nonskeletal site. Recently, we showed that the earliest steps occur in sensory nerves. We now extend these studies by identifying unique osteogenic progenitors within the endoneurial compartment of sensory nerves.

Hydrogel-based Delivery of rhBMP-2 Improves Healing of Large Bone Defects Compared With Autograft

Laxminarayanan Krishnan PhD, Lauren B. Priddy MS, Camden Esancy BS, Mon-Tzu Alice Li PhD, Hazel Y. Stevens BS, Xi Jiang BS, Lisa Tran MD, David W. Rowe PhD, Robert E. Guldberg PhD

Autologous bone grafting remains the gold standard in the treatment of large bone defects but is limited by tissue availability and donor site morbidity. Recombinant human bone morphogenetic protein-2 (rhBMP-2), delivered with a collagen sponge, is clinically used to treat large bone defects and complications such as delayed healing or nonunion. For the same dose of rhBMP-2, we have shown that a hybrid nanofiber mesh-alginate (NMA-rhBMP-2) delivery system provides longer-term release and increases functional bone regeneration in critically sized rat femoral bone defects compared with a collagen sponge. However, no comparisons of healing efficiencies have been made thus far between this hybrid delivery system and the gold standard of using autograft.

Immunomodulatory Peptide IDR-1018 Decreases Implant Infection and Preserves Osseointegration

Hyonmin Choe MD, PhD, Arvind S. Narayanan MS, Deep A. Gandhi, Aaron Weinberg DMD, PhD, Randall E. Marcus MD, Zhenghong Lee PhD, Robert A. Bonomo MD, Edward M. Greenfield PhD

Innate defense regulator peptide-1018 (IDR-1018) is a 12-amino acid, synthetic, immunomodulatory host defense peptide that can reduce soft tissue infections and is less likely to induce bacterial resistance than conventional antibiotics. However, IDRs have not been tested on orthopaedic infections and the immunomodulatory effects of IDR-1018 have only been characterized in response to lipopolysacharide, which is exclusively produced by Gram-negative bacteria.

Rifamycin Derivatives Are Effective Against Staphylococcal Biofilms In Vitro and Elutable From PMMA

Carlos J. Sanchez PhD, Stefanie M. Shiels PhD, David J. Tennent MD, Sharanda K. Hardy BS, Clinton K. Murray MD, Joseph C. Wenke PhD

Local antimicrobial delivery through polymethylmethacrylate beads (PMMA), commonly vancomycin, is used for the treatment of contaminated open fractures but has limited activity againstbiofilms, which occur commonly in such fractures. Rifamycins have activity against biofilms and are an effective treatment for osteoarticular infections involving staphylococcal biofilms, but there are limited studies evaluating the activity of rifamycin derivatives, other than rifampin, against biofilms ofand evaluating incorporation of these drugs into PMMA for treatment of contaminated open fractures.

Porphyrin-adsorbed Allograft Bone: A Photoactive, Antibiofilm Surface

Sana S. Dastgheyb PhD, Cyrus B. Toorkey PhD, Irving M. Shapiro BDS, PhD, Noreen J. Hickok PhD

Allograft bone is commonly used to augment bone stock. Unfortunately, allograft is prone to bacterial contamination and current antimicrobial therapies are inadequate. Photoactivated porphyrins combat bacterial growth by production of reactive oxygen species (ROS); however, to our knowledge, they have not been tested in the setting of allograft bone.

Blast Injury in the Spine: Dynamic Response Index Is Not an Appropriate Model for Predicting Injury

Edward Spurrier BM, FRCS(Tr+Orth), James A. G. Singleton MRCS, RAMC, Spyros Masouros PhD, Iain Gibb FRCS Ed, FRCR, RAMC, Jon Clasper DM, DPhil

Improvised explosive devices are a common feature of recent asymmetric conflicts and there is a persistent landmine threat to military and humanitarian personnel. Assessment of injury risk to the spine in vehicles subjected to explosions was conducted using a standardized model, the Dynamic Response Index (DRI). However, the DRI was intended for evaluating aircraft ejection seats and has not been validated in blast conditions.

Bioburden Increases Heterotopic Ossification Formation in an Established Rat Model

Gabriel J. Pavey MD, Ammar T. Qureshi PhD, Donald N. Hope MD, Rebecca L. Pavlicek PhD, Benjamin K. Potter MD, Jonathan A. Forsberg MD, Thomas A. Davis PhD

Heterotopic ossification (HO) develops in a majority of combat-related amputations wherein early bacterial colonization has been considered a potential early risk factor. Our group has recently developed a small animal model of trauma-induced HO that incorporates many of the multifaceted injury patterns of combat trauma in the absence of bacterial contamination and subsequent wound colonization.

Botulinum Toxin-induced Muscle Paralysis Inhibits Heterotopic Bone Formation

Brandon J. Ausk PhD, Ted S. Gross PhD, Steven D. Bain PhD

Short-term muscle atrophy induced by botulinum toxin A (BTxA) has been observed to impair osteogenesis in a rat closed femur fracture model. However, it is unclear whether the underlying mechanism is a direct effect of BTxA on muscle-bone interactions or an indirect effect that is driven by skeletal unloading. Because skeletal trauma in the closed fracture model also leads to disuse atrophy, we sought to mitigate this confounding variable by examining BTxA effects on muscle-bone interactions in two complementary in vivo models in which osteogenesis is induced in the absence of skeletal unloading. The overall aim of this study was to identify a potential strategy to inhibit pathological bone formation and heterotopic ossification (HO).

Bone Regeneration Is Promoted by Orally Administered Bovine Lactoferrin in a Rabbit Tibial Distraction Osteogenesis Model

Wenyang Li PhD, Songsong Zhu PhD, Jing Hu PhD

Lactoferrin, an iron-binding glycoprotein which belongs to the transferrin family, has been shown to promote bone growth. However, reports regarding effects of lactoferrin on bone regeneration during distraction osteogenesis are limited. Our study was designed to investigate the effect of bovine lactoferrin treatment on bone formation of the distracted callus.

Are Changes in Composition in Response to Treatment of a Mouse Model of Osteogenesis Imperfecta Sex-dependent?

Adele L. Boskey PhD, Josephine Marino MPh, Lyudmila Spevak MS, Nancy Pleshko PhD, Stephen Doty PhD, Erin M. Carter MS, Cathleen L. Raggio MD

Osteogenesis imperfecta (OI) is a genetic disease characterized by skeletal fragility and deformity. There is extensive debate regarding treatment options in adults with OI. Antiresorptive treatment reduces the number of fractures in growingmice, an animal model that reproducibly mimics the moderate-to-severe form of OI in humans. Effects of long-term treatments with antiresorptive agents, considered for treatment of older patients with OI with similar presentation (moderate-to-severe OI) are, to date, unknown.