Adaptive Image Segmentation Reveals Substantial Cortical Bone Remodeling During Early Fracture Repair.

The goal of this study was to develop an image analysis algorithm for quantifying the effects of remodeling on cortical bone during early fracture healing. An adaptive thresholding technique with boundary curvature and tortuosity control was developed to automatically identify the endocortical and pericortical boundaries in the presence of high-gradient bone mineral density (BMD) near the healing zone. The algorithm successfully segmented more than 47,000 microCT images from 12 healing ovine osteotomies and intact contralateral tibiae.

Retrospective evaluation of radiofrequency volumetric tissue reduction for hypertrophic turbinates in dogs with brachycephalic obstructive airway syndrome.

Objective: The objective of this study was to retrospectively assess the effect of Radiofrequency Volumetric Tissue Reduction (RFVTR) on hypertrophic turbinates and clinical outcome in brachycephalic dogs when included in multi-level surgery (MLS).

Study Design: Clinical retrospective multicenter study.

Animals: 132 client-owned brachycephalic dogs.

Potent drug delivery enhancement of betulinic acid and NVX-207 into equine skin in vitro - a comparison between a novel oxygen flow-assisted transdermal application device and microemulsion gels.

Background: Gray horses are predisposed to equine malignant melanoma (EMM) with advancing age. Depending on the tumor's location and size, they can cause severe problems (e.g.

Poly(ADP-Ribose) Polymerases-Inhibitor Talazoparib Inhibits Muscle Atrophy and Fatty Infiltration in a Tendon Release Infraspinatus Sheep Model: A Pilot Study.

Structural muscle changes, including muscle atrophy and fatty infiltration, follow rotator cuff tendon tear and are associated with a high repair failure rate. Despite extensive research efforts, no pharmacological therapy is available to successfully prevent both muscle atrophy and fatty infiltration after tenotomy of tendomuscular unit without surgical repair. Poly(ADP-ribose) polymerases (PARPs) are identified as a key transcription factors involved in the maintenance of cellular homeostasis.

Studying Edema Formation After Release of the Infraspinatus Muscle as an Experimental Model of Rotator Cuff Lesions in Sheep: A Histological Analysis.

Background: Muscle edema formation and inflammatory processes are early manifestations of acute rotator cuff lesions in sheep. Histological analysis of affected muscles revealed edema formation, inflammatory changes, and muscle tissue disruption in MRs.

Hypothesis: Edema contributes to inflammatory reactions and early muscle fiber degeneration before the onset of fatty infiltration.

Rotator Cuff Repair and Overlay Augmentation by Direct Interlocking of a Nonwoven Polyethylene Terephthalate Patch Into the Tendon: Evaluation in an Ovine Model.

Background: Arthroscopic repair of large rotator cuff tendon tears is associated with high rates of retear. Construct failure often occurs at the suture-tendon interface. Patch augmentation can improve mechanical strength and healing at this interface.

Combined electric and magnetic field therapy for bone repair and regeneration: an investigation in a 3-mm and an augmented 17-mm tibia osteotomy model in sheep.

Background: Therapies using electromagnetic field technology show evidence of enhanced bone regeneration at the fracture site, potentially preventing delayed or nonunions.

Methods: Combined electric and magnetic field (CEMF) treatment was evaluated in two standardized sheep tibia osteotomy models: a 3-mm non-critical size gap model and a 17-mm critical size defect model augmented with autologous bone grafts, both stabilized with locking compression plates. CEMF treatment was delivered across the fracture gap twice daily for 90 min, starting 4 days postoperatively (post-OP) until sacrifice (9 or 12 weeks post-OP, respectively).

Effect of PARP-1 Inhibition on Rotator Cuff Healing: A Feasibility Study Using Veliparib in a Rat Model of Acute Rotator Cuff Repair.

Background: PARP-1 (poly[ADP-ribose]) was shown to influence the inflammatory response after rotator cuff tear, leading to fibrosis, muscular atrophy, and fatty infiltration in mouse rotator cuff degeneration. So far, it is not known how PARP-1 influences enthesis healing after rotator cuff tear repair.

Hypothesis/purpose: This study aimed to examine the feasibility of oral PARP-1 inhibition and investigate its influence on rat supraspinatus enthesis and muscle healing after rotator cuff repair.

Evaluation of the Potential of Umbilical Cord Mesenchymal Stromal Cell-Derived Small Extracellular Vesicles to Improve Rotator Cuff Healing: A Pilot Ovine Study.

Background: Despite significant advancements in surgical techniques to repair rotator cuff (RC) injuries, failure rates remain high and novel approaches to adequately overcome the natural biological limits of tendon and enthesis regeneration of the RC are required. Small extracellular vesicles (sEVs) derived from the secretome of human multipotent mesenchymal stromal cells (MSCs) have been demonstrated to modulate inflammation and reduce fibrotic adhesions, and therefore their local application could improve outcomes after RC repair.

Purpose: In this pilot study, we evaluated the efficacy of clinical-grade human umbilical cord (hUC) MSC-derived sEVs (hUC-MSC-sEVs) loaded onto a type 1 collagen scaffold in an ovine model of acute infraspinatus tendon injury to improve RC healing.

Oral Use of Therapeutic Carbon Monoxide for Anyone, Anywhere, and Anytime.

Carbon monoxide (CO) is a therapeutic gas with therapeutic potential in intestinal bowel disease. Therapeutic efficacy in the gastrointestinal tract (GIT) must be paired with safe and convenient use. Therefore, we designed an oral CO releasing system (OCORS) pairing tunable CO release into the GIT while preventing the release of any other molecule from within the device, causing safety concerns.

Histological Preparation and Evaluation of Cartilage Specimens.

In this chapter, an introduction is given into histological techniques to research related to hyaline cartilage and subchondral bone. Emphasis is placed on the importance to investigate cartilage and bone as a unit, which includes the transition zone of the calcified cartilage and tidemark. Reasons for the appropriate selection of histological methods are presented such as when to use (decalcified) specimens for routine paraffin embedding including immunohistology, cryosections of cartilage alone, or non-decalcified specimens for embedding in polymethylmethacrylate with or without additional biomaterials.

Studying Edema Formation After Release of the Infraspinatus Tendon as an Experimental Model of Rotator Cuff Tears in Sheep: A Preliminary Imaging and Morphological Analysis.

Background: The cause, extent, and role of muscle edema for muscle degeneration are unknown and not considered in the current literature. In vivo experiments were designed to prove muscle edema formation in the early period in a sheep model of acute rotator cuff tears.

Hypothesis: Muscle edema occurs after tendon release with or without additional stretching trauma and may be associated with muscle retraction and subsequent muscle degeneration.

A Bioinspired Orthopedic Biomaterial with Tunable Mechanical Properties Based on Sintered Titanium Fibers.

Inadequate mechanical compliance of orthopedic implants can result in excessive strain of the bone interface, and ultimately, aseptic loosening. It is hypothesized that a fiber-based biometal with adjustable anisotropic mechanical properties can reduce interface strain, facilitate continuous remodeling, and improve implant survival under complex loads. The biometal is based on strategically layered sintered titanium fibers.

Biomechanical duality of fracture healing captured using virtual mechanical testing and validated in ovine bones.

Bone fractures commonly repair by forming a bridging structure called callus, which begins as soft tissue and gradually ossifies to restore rigidity to the bone. Virtual mechanical testing is a promising technique for image-based assessment of structural bone healing in both preclinical and clinical settings, but its accuracy depends on the validity of the material model used to assign tissue mechanical properties. The goal of this study was to develop a constitutive model for callus that captures the heterogeneity and biomechanical duality of the callus, which contains both soft tissue and woven bone.

Optimizing large-scale autologous human keratinocyte sheets for major burns-Toward an animal-free production and a more accessible clinical application.

Background And Aims: Autologous keratinocyte sheets constitute an important component of the burn wound treatment toolbox available to a surgeon and can be considered a life-saving procedure for patients with severe burns over 50% of their total body surface area. Large-scale keratinocyte sheet cultivation still fundamentally relies on the use of animal components such as inactivated murine 3T3 fibroblasts as feeders, animal-derived enzymes such as trypsin, as well as media components such as fetal bovine serum (FBS). This study was therefore aimed to optimize autologous keratinocyte sheets by comparing various alternatives to critical components in their production.

Image-based radiodensity profilometry measures early remodeling at the bone-callus interface in sheep.

Bone healing has been traditionally described as a four-phase process: inflammatory response, soft callus formation, hard callus development, and remodeling. The remodeling phase has been largely neglected in most numerical mechanoregulation models of fracture repair in favor of capturing early healing using a pre-defined callus domain. However, in vivo evidence suggests that remodeling occurs concurrently with repair and causes changes in cortical bone adjacent to callus that are typically neglected in numerical models of bone healing.

Transplant of Autologous Mesenchymal Stem Cells Halts Fatty Atrophy of Detached Rotator Cuff Muscle After Tendon Repair: Molecular, Microscopic, and Macroscopic Results From an Ovine Model.

Background: The injection of mesenchymal stem cells (MSCs) mitigates fat accumulation in released rotator cuff muscle after tendon repair in rodents.

Purpose: To investigate whether the injection of autologous MSCs halts muscle-to-fat conversion after tendon repair in a large animal model for rotator cuff tendon release via regional effects on extracellular fat tissue and muscle fiber regeneration.

Study Design: Controlled laboratory study.

Engineered nasal cartilage for the repair of osteoarthritic knee cartilage defects.

Osteoarthritis (OA) is the most prevalent joint disorder, causing pain and disability predominantly in the aging population but also affecting young individuals. Current treatments are limited to use of anti-inflammatory drugs to alleviate symptoms or degenerated joint replacement by a prosthetic implant at the end stage of the disease. We hypothesized that degenerative cartilage defects can be treated using nasal chondrocyte–based tissue-engineered cartilage (N-TEC).

Muscle Degeneration Induced by Sequential Release and Denervation of the Rotator Cuff Tendon in Sheep.

Background: In a sheep rotator cuff model, tenotomy predominantly induces fatty infiltration, and denervation induces mostly muscle atrophy. In clinical practice, myotendinous retraction after tendon tear or lateralization after tendon repair tear may lead to traction injury of the nerve.

Purpose/hypothesis: To analyze whether an additional nerve lesion during rotator cuff repair leads to further degeneration of the rotator cuff muscle in the clinical setting.

Preclinical Testing of New Hydrogel Materials for Cartilage Repair: Overcoming Fixation Issues in a Large Animal Model.

Reinforced hydrogels represent a promising strategy for tissue engineering of articular cartilage. They can recreate mechanical and biological characteristics of native articular cartilage and promote cartilage regeneration in combination with mesenchymal stromal cells. One of the limitations of models for testing the outcome of tissue engineering approaches is implant fixation.

Establishment of a localized acute implant-associated Staphylococcus aureus bone infection model in sheep.

Orthopedic implant-associated bacterial infections with Staphylococcus aureus constitute a major clinical problem, and large pre-clinical animal models remain scarce. The aim of this study was to establish a standardized method of a localized, acute S. aureus bone infection in the presence of complex implanted devices in a sheep model.

Industrial Development of Standardized Fetal Progenitor Cell Therapy for Tendon Regenerative Medicine: Preliminary Safety in Xenogeneic Transplantation.

Tendon defects require multimodal therapeutic management over extensive periods and incur high collateral burden with frequent functional losses. Specific cell therapies have recently been developed in parallel to surgical techniques for managing acute and degenerative tendon tissue affections, to optimally stimulate resurgence of structure and function. Cultured primary human fetal progenitor tenocytes (hFPT) have been preliminarily considered for allogeneic homologous cell therapies, and have been characterized as stable, consistent, and sustainable cell sources in vitro.