Thomas Schaer | University of Pennsylvania (original) (raw)

Papers by Thomas Schaer

Frontiers in allergy, Feb 13, 2024

The FASEB Journal, Dec 11, 2023

OTA international, Mar 1, 2024

A69. AN IMAGE'S WORTH: STUDIES IN LUNG IMAGING

The Journal of Nuclear Medicine, 2010

1471 Objectives Liposomes are phospholipid nanoparticles that extravasate at sites of increased v... more 1471 Objectives Liposomes are phospholipid nanoparticles that extravasate at sites of increased vascular permeability. They are used for targeted drug delivery and diagnostic imaging. This study is the first to describe the i.v. administration of Tc-99m labeled polyethylene glycol (PEG)-coated liposomes in normal horses. Methods Liposomes containing glutathione were prepared via the film hydration method and labeled using Tc-99m-HMPAO. An assay was developed to establish the 50% serum hemolytic complement activity (CH50) in horses, as complement-mediated reactions are a common adverse effect in other species. Ten horses were administered Tc-99m PEG-liposomes i.v.. Clinical parameters, hematology, plasma biochemistry and serum complement activity were monitored serially. Imaging was performed at 1, 12, and 21 h p.i.. Six horses were euthanized at 23 h and tissues of interest were dissected and uptake was calculated as %ID/kg. Results Complement assays required the addition of C3 depl...

Dense fibrous connective tissues play critical load-bearing roles in the musculoskeletal system a... more Dense fibrous connective tissues play critical load-bearing roles in the musculoskeletal system and represent a significant medical problem when their function is interrupted by progressive degeneration or acute injury. The intent of this chapter is to outline the functional aspects of two such tissues, the fibrocartilaginous knee meniscus and the annulus fibrosus of the intervertebral disc of the spine. In this chapter, we discuss the hallmark mechanical and biochemical features of each of these tissues, the incidence and most common means through which these tissues are damaged or degenerated, and the current clinical practices for their repair or replacement. Given the prevalence of damage to these tissues, numerous commercial products are, or will soon be, available in the marketplace; these products are discussed in the context of native tissue structure and function and the engineering principles and biomaterial components governing their design. Next, new products, based on t...

TP125. TP125 STRUCTURE AND FUNCTION IN THE PEDIATRIC LUNG, 2021

Cette invention a pour objet un nucleus pulposus, situe dans la region de l’axe central (110) d’u... more Cette invention a pour objet un nucleus pulposus, situe dans la region de l’axe central (110) d’un disque intervertebral (106) au sein de l’anneau fibreux (108), complete ou remplace en procedant a l’introduction d’une certaine proportion d’une substance biocompatible dans la region de l’axe central en suivant un procede incluant plusieurs etapes : la formation d’un canal (116) traversant l’element vertebral (102), contigu avec ledit disque intervertebral, s’etirant depuis une surface exterieure de l’element vertebral jusqu’a la zone de l’axe central de l’anneau fibreux ; 2) l’introduction d’une certaine proportion de substance biocompatible, par ce canal, dans la region de l’axe central de l’anneau fibreux ; 3) la pressurisation de la substance biocompatible par le canal, a une pression post-operatoire suffisante pour permettre de minimiser les symptomes du nucleus pulposus degenere ; et 4) la fixation du canal tandis que la pression post-operatoire minimale est maintenue.

Journal of Ultrasound in Medicine, May 30, 2023

This study investigated the combination of antibiotics and ultrasound triggered microbubble destr... more This study investigated the combination of antibiotics and ultrasound triggered microbubble destruction (UTMD) to disrupt free-floating bacterial biofilms in synovial fluid (SynF) of infected joints. In vitro, 1x107 colony forming units (CFU) of S. aureus aggregated in human SynF had 100mumathrmL100\ \mu\mathrm{L}100mumathrmL of Definity® (Lantheus Medical Imaging, N Billerica, MA, USA), and 30mumathrmg/textmL30\ \mu\mathrm{g}/\text{mL}30mumathrmg/textmL of amikacin added. Samples were insonated either at a high MI of 1.06 for 10 min or a low MI of 0.04 for 6 min. In vivo, 6 pigs (mean weight 35 kg) had their left femorotibial joint inoculated with 1x106 CFU of S. aureus. A SynF sample was collected from all animals 24 hrs post-inoculation. Control animals (2) received amikacin (250 mg) into the joint, while the remaining animals received 100mumathrmL100\ \mu\mathrm{L}100mumathrmL of Definity and 1 mL of amikacin. UTMD was performed using an S9 Pro scanner with a curvilinear probe (SonoScape, Shenzhen, China) and a flash replenishment sequence ($\text{MI} < 0.15$) with 4 sss destructive pulses ($\text{MI} > 0.6$) for the duration of contrast visualization. SynF samples were collected from all animals after the therapeutic intervention for cytological analysis and quantitative bacteriology. UTMD and antibiotics resulted in large decreases in bacterial numbers (>2-4 logs) in vitro compared to antibiotic alone. In vivo the infection protocol consistently caused clinical septic arthritis by 24 hrs post-inoculation. Nucleated cell counts and cytology parameters were all consistent with septic arthritis. Floating bacterial aggregates were occasionally observed in the joint aspirates obtained prior to UTMD. No biofloats were detected on joint aspirates obtained following intra-articular therapy and no bacterial growth was noted in any dilutions in the post-treatment SynF samples, while pre-treatment samples and amikacin only animals presented with bacterial counts of greater than 2000 CFU/mL. In conclusion, UTMD demonstrates synergism with antimicrobials against SynF biofilm aggregates.

Osteoarthritis and Cartilage, 2017

Objective: The objective of this study was to establish a large animal model that recapitulates t... more Objective: The objective of this study was to establish a large animal model that recapitulates the spectrum of intervertebral disc degeneration that occurs in humans and which is suitable for pre-clinical evaluation of a wide range of experimental therapeutics. Design: Degeneration was induced in the lumbar intervertebral discs of large frame goats by either intradiscal injection of chondroitinase ABC (ChABC) over a range of dosages (0.1U, 1U or 5U) or subtotal nucleotomy. Radiographs were used to assess disc height changes over 12 weeks. Degenerative changes to the discs and endplates were assessed via magnetic resonance imaging (MRI), semi-quantitative histological grading, microcomputed tomography (mCT), and measurement of disc biomechanical properties. Results: Degenerative changes were observed for all interventions that ranged from mild (0.1U ChABC) to moderate (1U ChABC and nucleotomy) to severe (5U ChABC). All groups showed progressive reductions in disc height over 12 weeks. Histological scores were significantly increased in the 1U and 5U ChABC groups. Reductions in T2 and T1r, and increased Pfirrmann grade were observed on MRI. Resorption and remodeling of the cortical boney endplate adjacent to ChABC-injected discs also occurred. Spine segment range of motion (ROM) was greater and compressive modulus was lower in 1U ChABC and nucleotomy discs compared to intact. Conclusions: A large animal model of disc degeneration was established that recapitulates the spectrum of structural, compositional and biomechanical features of human disc degeneration. This model may serve as a robust platform for evaluating the efficacy of therapeutics targeted towards varying degrees of disc degeneration.

Equine Veterinary Journal, Jun 23, 2011

Reasons for performing study: Liposomes are phospholipid nanoparticles that extravasate at sites ... more Reasons for performing study: Liposomes are phospholipid nanoparticles that extravasate at sites of increased vascular permeability. They have potential in equine medicine for targeted drug delivery and diagnostic imaging of infectious, inflammatory and neoplastic lesions. Objectives: This study evaluates the safety and biodistribution of i.v. polyethyleneglycol(PEG) liposomes in normal horses. Methods: PEG-liposomes were prepared by the film hydration method and labelled using 99m Tc-hexamethyl-propylene-amine-oxime. A single dose of 0.24 mmol/kg bwt 99m Tc-PEG-liposomes and 2.4 mmol/kg bwt unlabelled PEG-liposomes was administered to 10 conscious horses via i.v. infusion at a rate of 6 mmol/min for the first 15 min and 60 mmol/min thereafter. Clinical parameters, haematology, plasma biochemistry and serum complement activity were monitored serially. Scintigraphic imaging was performed at 1, 12 and 21 h post infusion (PI). Six horses were subjected to euthanasia at 24 h PI. The percentage injected dose per kilogram of tissue was calculated for multiple organs. Results were analysed using repeated measures ANOVA. Results: Horses did not demonstrate adverse reactions during or after liposome infusion. There was a significant elevation in heart rate and respiratory rate at 20 and 25 min PI. No significant complement consumption was detected, although a trend for decreased total haemolytic complement values at 20 min PI was present. Scintigraphic studies revealed a prolonged vascular phase that lasted to 21 h PI, with a reproducible pattern of organ distribution. Biodistribution studies revealed the highest concentrations of radiopharmaceutical within the lung, kidney, liver and spleen. Conclusions: Intravenous liposome administration appears to be safe in horses. When administered in combination with PEG-liposomes, 99m Tc-PEG-liposomes have long circulating characteristics and a reproducible pattern of organ distribution in horses. Potential relevance: Radiolabelled liposomes may be useful for detecting infection, inflammation and neoplasia in the horse. Liposomes have significant potential for targeted drug delivery in the horse. This study establishes the scintigraphic findings and tissue distribution of 99mTc-PEG-liposomes after i.v. administration in healthy horses.

bioRxiv (Cold Spring Harbor Laboratory), Oct 23, 2022

Tension-activated repair patches delivering bioactive anti-inflammatory factors improve healing i... more Tension-activated repair patches delivering bioactive anti-inflammatory factors improve healing in an in vivo goat cervical disc injury model.

Osteoarthritis and Cartilage, Apr 1, 2021

$Research paper thumbnail of Retrospective study of orthopedic infections in equine long bone fractures treated by internal fixation: 192 cases (1990-2006)$

bioRxiv (Cold Spring Harbor Laboratory), May 22, 2023

Intervertebral disc degeneration is a leading cause of chronic low back pain. Cell-based strategi... more Intervertebral disc degeneration is a leading cause of chronic low back pain. Cell-based strategies that seek to treat disc degeneration by regenerating the central nucleus pulposus hold significant promise, but key challenges remain. One of these is the inability of therapeutic cells to effectively mimic the performance of native nucleus pulposus cells, which are unique amongst skeletal cell types in that they arise from the embryonic notochord. In this study we use single cell RNA sequencing to demonstrate emergent heterogeneity amongst notochord-derived nucleus pulposus cells in the postnatal mouse disc. Specifically, we established the existence of early and late stage nucleus pulposus cells, corresponding to notochordal progenitor and mature cells, respectively. Late stage cells exhibited significantly higher expression levels of extracellular matrix genes including aggrecan, and collagens II and VI, along with elevated TGF-β and PI3K-Akt signaling. Additionally, we identified Cd9 as a novel surface marker of late stage nucleus pulposus cells, and demonstrated that these cells were localized to the nucleus pulposus periphery, increased in numbers with increasing postnatal age, and co-localized with emerging glycosaminoglycan-rich matrix. Finally, we used a goat model to show the Cd9+ nucleus pulposus cell numbers decrease with moderate severity disc degeneration, suggesting that these cells are associated with maintenance of the healthy nucleus pulposus extracellular matrix. Improved understanding of the developmental mechanisms underlying regulation of ECM deposition in the postnatal NP may inform improved regenerative strategies for disc degeneration and associated low back pain.

Advanced Materials Interfaces, Sep 13, 2022

Bacterial contamination of an exposed implantable medical device by the atmosphere of an operatin... more Bacterial contamination of an exposed implantable medical device by the atmosphere of an operating room (OR) is increasingly implicated as a cause of device‐associated infection. Here, OR contamination is modeled in vitro using an aerosolizing system to spray small quantities of staphylococci onto titanium rods. Contaminated rods always manifest culturable bacteria. Self‐assembly is used to create a self‐defensive Ti surface that substantially enhances the rod's resistance to such contamination. Poly(acrylic acid) microgels are electrostatically deposited onto small Ti rods and subsequently loaded by complexation with a cationic antimicrobial peptoid (TM1). The microgels are visualized in situ by optical microscopy, and changes in microgel diameter indicate the loading state. These measurements show that TM1 can be quickly loaded from low‐ionic‐strength buffer and subsequently remained sequestered within the microgels for up to 4 weeks when soaked in phosphate buffered saline. TM1‐loaded microgel‐modified Ti surfaces are contaminated with aerosolized staphylococci, and subsequent assays indicate few or no culturable bacteria. In the absence of nutrients to enable metabolism, this finding suggests that bacteria trigger local TM1 release by contact transfer. The modified surfaces exhibit good in vitro cytocompatibility as manifested by the adhesion, spreading, and metabolic activity of human fetal osteoblasts.