Osteoarthritis as a Systemic Disease Promoted Prostate Cancer In Vivo and In Vitro.

Osteoarthritis (OA) is increasing worldwide, and previous work found that OA increases systemic cartilage oligomeric matrix protein (COMP), which has also been implicated in prostate cancer (PCa). As such, we sought to investigate whether OA augments PCa progression. Cellular proliferation and migration of RM1 murine PCa cells treated with interleukin (IL)-1α, COMP, IL-1α + COMP, or conditioned media from cartilage explants treated with IL-1α (representing OA media) and with inhibitors of COMP were assessed.

An Innovative Seven-year Physician Scientist Residency Training Program That Addresses the Shortage of Academic Surgeons.

Due to the declining number of scientifically trained physicians and increasing demand for high-quality literature, our institution pioneered a seven-year Physician Scientist Training Program (PSTP) to provide research-oriented residents the knowledge and skills for a successful academic career. The present study sought to identify orthopaedic surgeons with MD/PhD degrees, residency programs with dedicated research tracks, and to assess the effectiveness of the novel seven-year program in training prospective academic orthopaedic surgeons. Surgeons with MD/PhD degrees account for 2.

Peripheral Nerve Regeneration with Acellular Nerve Allografts Seeded with Amniotic Fluid-Derived Stem Cells.

Introduction: Tissue engineering strategies have attempted to mimic regenerating axons' environment by adding supportive types of cells other than Schwann cell to the nerve allograft. We hypothesized that allografts can be seeded with amniotic fluid-derived stem cells (AFS) to promote nerve regeneration.

Methods: ANAs with AFS cells for long-gap nerve repairs were studied using a rat model.

Pharmacologic Recruitment of Endogenous Neural Stem/Progenitor Cells for the Treatment of Spinal Cord Injury.

Study Design: Laboratory study using a rat T9 contusion model of spinal cord injury.

Objective: This study aims to examine whether a combinatory treatment of Pioglitazone (PGZ) and granulocyte colony-stimulating factor (GCSF) can support neural stem/progenitor cells (NSPCs) directly and provide a sustainable microenvironment through immunomodulatory mechanisms.

Summary Of Background Data: Neuroinflammation plays a crucial role in the progression of spinal cord injury (SCI) and hinders NSPC-mediated repair and regeneration.

Keratin Biomaterials Improve Functional Recovery in a Rat Spinal Cord Injury Model.

Study Design: Laboratory study using a rat T9 contusion model of spinal cord injury (SCI).

Objective: The purpose of this study was to evaluate which method of delivery of soluble keratin biomaterials would best support functional restoration through the macrophage polarization paradigm.

Summary Of Background Data: SCI is a devastating neurologic event with complex pathophysiological mechanisms that currently has no cure.

Improved Antitumor Activity of the Fluoropyrimidine Polymer CF10 in Preclinical Colorectal Cancer Models through Distinct Mechanistic and Pharmacologic Properties.

Chemotherapy regimens that include 5-fluorouracil (5-FU) are central to colorectal cancer treatment; however, risk/benefit concerns limit 5-FU's use, necessitating development of improved fluoropyrimidine (FP) drugs. In our study, we evaluated a second-generation nanoscale FP polymer, CF10, for improved antitumor activity. CF10 was more potent than the prototype FP polymer F10 and much more potent than 5-FU in multiple colorectal cancer cell lines including HCT-116, LS174T, SW480, and T84D.

Improved osseointegration using porcine xenograft compared to demineralized bone matrix for the treatment of critical defects in a small animal model.

Background: Autograft (AG) is the gold standard bone graft due to biocompatibility, osteoconductivity, osteogenicity, and osteoinductivity. Alternatives include allografts and xenografts (XG).

Methods: We investigated the osseointegration and biocompatibility of a decellularized porcine XG within a critical defect animal model.

Success and efficiency of cell seeding in Avian Tendon Xenografts - A promising alternative for tendon and ligament reconstruction.

Decellularized tendon xenografts offer a promising alternative for reconstruction by using ubiquitously available material. This study compares static and centrifugal seeding of avian tendon scaffolds with NIH 3T3 fibroblasts. Incorporation of viable cells was achievable with both techniques, represented by DNA content.

Altered rodent gait characteristics after ~35 days in orbit aboard the International Space Station.

The long-term adaptations to microgravity and other spaceflight challenges within the confines of a spacecraft, and readaptations to weight-bearing upon reaching a destination, are unclear. While post-flight gait change in astronauts have been well documented and reflect multi-system deficits, no data from rodents have been collected. Thus, the purpose of this study was to evaluate gait changes in response to spaceflight.

Investigating the Osteoinductive Potential of a Decellularized Xenograft Bone Substitute.

Bone grafting is the second most common tissue transplantation procedure worldwide. One of the alternative methods for bone repair under investigation is a tissue-engineered bone substitute. An ideal property of tissue-engineered bone substitutes is osteoinductivity, defined as the ability to stimulate primitive cells to differentiate into a bone-forming lineage.

A porcine xenograft-derived bone scaffold is a biocompatible bone graft substitute: An assessment of cytocompatibility and the alpha-Gal epitope.

Background: Xenografts are an attractive alternative to traditional bone grafts because of the large supply from donors with predictable morphology and biology as well as minimal risk of human disease transmission. Clinical series involving xenograft bone transplantation, most commonly from bovine sources, have reported poor results with frequent graft rejection and failure to integrate with host tissue. Failures have been attributed to residual alpha-Gal epitope in the xenograft which humans produce natural antibody against.

Ascorbic Acid and Its Clinical Role in Orthopaedic Surgery.

Ascorbic acid (vitamin C) is an essential micronutrient with evidence supporting its role in bone formation, tissue repair, and collagen production. Its clinical importance to the field of orthopaedic surgery has yet to be fully defined. Several observational studies have shown improved bone density and reduced hip fracture risk with supplementation.

Nerve Repair with Nerve Conduits: Problems, Solutions, and Future Directions.

Nerve conduits are becoming increasingly popular for the repair of peripheral nerve injuries. Their ease of application and lack of donor site morbidity make them an attractive option for nerve repair in many situations. Today, there are many different conduits to choose in different sizes and materials, giving the reconstructive surgeon many options for any given clinical problem.

Evaluation of Percutaneous Intradiscal Amniotic Suspension Allograft in a Rabbit Model of Intervertebral Disc Degeneration.

Study Design: A laboratory study using a rabbit annular puncture model of intervertebral disc degeneration (IDD).

Objective: The aims of this study were to assess whether an amniotic suspension allograft (ASA) containing particulated human amnion and amniotic fluid derived cells regains intervertebral disc height and morphology and improves histologic scoring in a rabbit model of IDD.

Summary Of Background Data: In contrast to current surgical interventions for IDD, in which the primary goal is to relieve symptomatic pain, one novel strategy involves the direct injection of anabolic cytokines.

A percutaneous, minimally invasive annulus fibrosus needle puncture model of intervertebral disc degeneration in rabbits.

Purpose: Various animal models have been proposed to mimic the pathophysiologic process of intervertebral disc degeneration, a leading cause of back pain. The purpose of this study is to describe a minimally invasive technique via percutaneous needle puncture of the annulus fibrosus in New Zealand white rabbits.

Methods: Under fluoroscopic guidance, an 18-gauge spinal needle was inserted 2 cm lateral to the midline spinous process.

A Decellularized Porcine Xenograft-Derived Bone Scaffold for Clinical Use as a Bone Graft Substitute: A Critical Evaluation of Processing and Structure.

Background: Bone grafts are used in approximately one half of all musculoskeletal surgeries. Autograft bone is the historic gold standard but is limited in supply and its harvest imparts significant morbidity to the patient. Alternative sources of bone graft include allografts, synthetics and, less commonly, xenografts which are taken from animal species.

Age-Dependent Schwann Cell Phenotype Regulation Following Peripheral Nerve Injury.

Background: Schwann cells are integral to the regenerative capacity of the peripheral nervous system, which declines after adolescence. The mechanisms underlying this decline are poorly understood. This study sought to compare the protein expression of Notch, c-Jun, and Krox-20 after nerve crush injury in adolescent and young adult rats.

The Development of a Xenograft-Derived Scaffold for Tendon and Ligament Reconstruction Using a Decellularization and Oxidation Protocol.

Purpose: To evaluate the biological, immunological, and biomechanical properties of a scaffold derived by architectural modification of a fresh-frozen porcine patella tendon using a decellularization protocol that combines physical, chemical, and enzymatic modalities.

Methods: Porcine patellar tendons were processed using a decellularization and oxidation protocol that combines physical, chemical, and enzymatic modalities. Scaffolds (n = 88) were compared with native tendons (n = 70) using histologic, structural (scanning electron microscopy, porosimetry, and tensile testing), biochemical (mass spectrometry, peracetic acid reduction, DNA quantification, alpha-galactosidase [α-gal] content), as well as in vitro immunologic (cytocompatibility, cytokine induction) and in vivo immunologic nonhuman primate analyses.

Nonsteroidal Anti-Inflammatory Drugs and Bone-Healing: A Systematic Review of Research Quality.

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are often avoided by orthopaedic surgeons because of their possible influence on bone-healing. This belief stems from multiple studies, in particular animal studies, that show delayed bone-healing or nonunions associated with NSAID exposure. The purpose of this review was to critically analyze the quality of published literature that evaluates the impact of NSAIDs on clinical bone-healing.

The regenerative effects of electromagnetic field on spinal cord injury.

Traumatic spinal cord injury (SCI) is typically the result of direct mechanical impact to the spine, leading to fracture and/or dislocation of the vertebrae along with damage to the surrounding soft tissues. Injury to the spinal cord results in disruption of axonal transmission of signals. This primary trauma causes secondary injuries that produce immunological responses such as neuroinflammation, which perpetuates neurodegeneration and cytotoxicity within the injured spinal cord.

Prostate-specific membrane antigen-targeted liposomes specifically deliver the Zn(2+) chelator TPEN inducing oxidative stress in prostate cancer cells.

Aim: To evaluate the potential use of zinc chelation for prostate cancer therapy using a new liposomal formulation of the zinc chelator, N,N,N',N'-tetrakis(2-pyridylmethyl)-ethylenediamine (TPEN).

Materials & Methods: TPEN was encapsulated in nontargeted liposomes or liposomes displaying an aptamer to target prostate cancer cells overexpression prostate-specific membrane antigen. The prostate cancer selectivity and therapeutic efficacy of liposomal (targeted and nontargeted) and free TPEN were evaluated in vitro and in tumor-bearing mice.

Effects of age and insulin-like growth factor-1 on rat neurotrophin receptor expression after nerve injury.

Introduction: Neurotrophin receptors, such as p75(NTR) , direct neuronal response to injury. Insulin-like growth factor-1 receptor (IGF-1R) mediates the increase in p75(NTR) during aging. The aim of this study was to examine the effect of aging and insulin-like growth factor-1 (IGF-1) treatment on recovery after peripheral nerve injury.

Angiotensin-(1-7) Attenuates Skeletal Muscle Fibrosis and Stiffening in a Mouse Model of Extremity Sarcoma Radiation Therapy.

Background: Radiation-induced fibrosis (RIF) of musculoskeletal tissue is a common complication of radiation therapy for extremity soft-tissue sarcoma, with no standardized strategy for prevention and treatment. Angiotensin-(1-7) (Ang-[1-7]), a well-tolerated endogenous heptapeptide hormone with antitumor and antifibrotic properties, was tested as a radioprotectant for RIF and stiffening of irradiated muscles.

Methods: Male CD-1 mice were randomized to one of three treatment groups: control, simulated sarcoma radiation therapy to the gastrocnemius and soleus muscles, or radiation therapy along with continuous Ang-(1-7) delivery initiated three days before radiation therapy.

A chronically-denervated versus a freshly-harvested autograft for nerve repair in rats.

Objectives: Autologous nerve grafting remains the gold standard for repair of peripheral nerve injuries. Its use, however, is limited by donor nerve availability and donor site morbidity. This is especially problematic after failure of an initial autograft that requires a repeat nerve graft, resulting in a second surgical site with associated morbidity.