Targeted nanomedicines for the treatment of bone disease and regeneration.

Targeted delivery by either passive or active targeting of therapeutics to the bone is an attractive treatment for various bone related diseases such as osteoporosis, osteosarcoma, multiple myeloma, and metastatic bone tumors. Engineering novel drug delivery carriers can increase therapeutic efficacy and minimize the risk of side effects. Developmnet of nanocarrier delivery systems is an interesting field of ongoing studies with opportunities to provide more effective therapies.

Decreasing Resource Utilization Using Standardized Clinical Assessment and Management Plans (SCAMPs).

Background: Standardized clinical assessment and management plans (SCAMPs) are a novel quality improvement initiative shown to improve patient care, diminish practice variation, and reduce resource utilization. Unlike clinical practice guidelines, a SCAMP is a flexible algorithm that undergoes iterative updates based on periodic data collection and review. We recently implemented a SCAMP for the closed treatment of pediatric torus fractures.

Achieving Microsurgical Competency in Orthopaedic Residents Utilizing a Self-Directed Microvascular Training Curriculum.

Background: Education in microvascular surgery is limited by variable experience, a difficult learning curve, and potentially catastrophic complications caused by failed anastomoses. Furthermore, utilization of live-animal training models can be difficult because of lack of access and high maintenance costs. The purpose of this study was to determine the effectiveness and cost of a self-directed microvascular training curriculum utilizing synthetic microvessels and nonliving models in an orthopaedic residency program.

Nanomedicine for safe healing of bone trauma: Opportunities and challenges.

Historically, high-energy extremity injuries resulting in significant soft-tissue trauma and bone loss were often deemed unsalvageable and treated with primary amputation. With improved soft-tissue coverage and nerve repair techniques, these injuries now present new challenges in limb-salvage surgery. High-energy extremity trauma is pre-disposed to delayed or unpredictable bony healing and high rates of infection, depending on the integrity of the soft-tissue envelope.

Cost of Immediate Surgery Versus Non-operative Treatment for Trigger Finger in Diabetic Patients.

Purpose: As health care costs continue to rise, providers must increasingly identify and implement cost-effective practice measures without sacrificing quality of care. Corticosteroid injections are an established treatment for trigger finger; however, numerous clinical trials have documented the limited efficacy of these injections in the diabetic population. Furthermore, the most cost-effective treatment strategy for diabetic trigger finger has not been determined.

The Calcium-Binding Protein S100A6 Accelerates Human Osteosarcoma Growth by Promoting Cell Proliferation and Inhibiting Osteogenic Differentiation.

Background/aims: Although osteosarcoma (OS) is the most common primary malignancy of bone, its molecular pathogenesis remains to be fully understood. We previously found the calcium-binding protein S100A6 was expressed in ∼80% of the analyzed OS primary and/or metastatic tumor samples. Here, we investigate the role of S100A6 in OS growth and progression.

Radiographic Evaluation During Treatment of Pediatric Forearm Fractures: Implications on Clinical Care and Cost.

Background: As ≥30% of displaced pediatric forearm fractures demonstrate loss of reduction (LOR) following closed reduction (CR); radiographic follow-up is advocated at 1, 2, 4, and 6 weeks for detection of redisplacement. We hypothesized that there is minimal change in fracture alignment 2 weeks after CR, and consequently, that radiographs at 4 weeks add cost but little value to clinical care.

Methods: A total of 184 patients enrolled in a prospective study of pediatric forearm fractures including both distal and diaphyseal injuries were evaluated.

Modified Protocol Decreases Surgical Site Infections after Total Knee Arthroplasty.

We investigate the effectiveness of a comprehensive aseptic protocol in reducing surgical site infection (SSI) after knee arthroplasty in a single medical center with a high prevalence of MRSA. A database of all patients in a single center undergoing primary knee arthroplasty between 2005 and 2011 was reviewed for SSI using Centers for Disease Control criteria and AAOS guidelines. All patients were treated with an aseptic protocol consisting of the following: preoperative 2% mupirocin nasal ointment and 0.

Reversibly Immortalized Mouse Articular Chondrocytes Acquire Long-Term Proliferative Capability While Retaining Chondrogenic Phenotype.

Cartilage tissue engineering holds great promise for treating cartilaginous pathologies including degenerative disorders and traumatic injuries. Effective cartilage regeneration requires an optimal combination of biomaterial scaffolds, chondrogenic seed cells, and biofactors. Obtaining sufficient chondrocytes remains a major challenge due to the limited proliferative capability of primary chondrocytes.

The E-F hand calcium-binding protein S100A4 regulates the proliferation, survival and differentiation potential of human osteosarcoma cells.

Background/aims: Osteosarcoma (OS) is the most common primary bone malignancy in children and young adults. Molecular mechanisms underlying the pathogenesis of OS remain to be fully understood. Several members of the E-F hand calcium-binding S100 protein family are differentially expressed in human cancers.

IGFBP5 domains exert distinct inhibitory effects on the tumorigenicity and metastasis of human osteosarcoma.

Osteosarcoma (OS) is the most common primary malignancy of bone. We investigated the roles of insulin-like growth factor binding protein 5 (IGFBP5) domains in modulating OS tumorigenicity and metastasis. The N-terminal (to a lesser extent the C-terminal) domain inhibited cell proliferation and induced apoptosis while the C-terminal domain inhibited cell migration and invasion.

A novel scoring system for assessing Chiari malformation type I treatment outcomes.

Background: Outcome assessment for the management of Chiari malformation type 1 is difficult because of the lack of a reliable and specific surgical outcome assessment scale. Such a scale could reliably correlate postoperative outcomes with preoperative symptoms.

Objective: We developed a novel scoring system and applied it retrospectively to 146 patients treated at our institution in order to create and verify a simple and quantifiable assessment of Chiari outcomes.

Epigenetic regulation of mesenchymal stem cells: a focus on osteogenic and adipogenic differentiation.

Stem cells are characterized by their capability to self-renew and terminally differentiate into multiple cell types. Somatic or adult stem cells have a finite self-renewal capacity and are lineage-restricted. The use of adult stem cells for therapeutic purposes has been a topic of recent interest given the ethical considerations associated with embryonic stem (ES) cells.

BMP-9 induced osteogenic differentiation of mesenchymal stem cells: molecular mechanism and therapeutic potential.

Promoting osteogenic differentiation and efficacious bone regeneration have the potential to revolutionize the treatment of orthopaedic and musculoskeletal disorders. Mesenchymal Stem Cells (MSCs) are bone marrow progenitor cells that have the capacity to differentiate along osteogenic, chondrogenic, myogenic, and adipogenic lineages. Differentiation along these lineages is a tightly controlled process that is in part regulated by the Bone Morphogenetic Proteins (BMPs).

Defective osteogenic differentiation in the development of osteosarcoma.

Osteosarcoma (OS) is associated with poor prognosis due to its high incidence of metastasis and chemoresistance. It often arises in areas of rapid bone growth in long bones during the adolescent growth spurt. Although certain genetic conditions and alterations increase the risk of developing OS, the molecular pathogenesis is poorly understood.

Minimally invasive pouch surgery for ulcerative colitis: is there a benefit in staging?

Background: With the introduction of biologic agents, medical and surgical management of ulcerative colitis has been associated with significant morbidity. A staged surgical approach is advocated to obviate the risks of infectious complication and consequent poor pouch function.

Objective: The aim of this study was to analyze the outcomes of our selective staged approaches in patients with ulcerative colitis who were undergoing laparoscopic pouch surgery.

Lysophosphatidic acid acyltransferase β (LPAATβ) promotes the tumor growth of human osteosarcoma.

Background: Osteosarcoma is the most common primary malignancy of bone with poorly characterized molecular pathways important in its pathogenesis. Increasing evidence indicates that elevated lipid biosynthesis is a characteristic feature of cancer. We sought to investigate the role of lysophosphatidic acid acyltransferase β (LPAATβ, aka, AGPAT2) in regulating the proliferation and growth of human osteosarcoma cells.

Tetrandrine inhibits Wnt/β-catenin signaling and suppresses tumor growth of human colorectal cancer.

As one of the most common malignancies, colon cancer is initiated by abnormal activation of the Wnt/β-catenin pathway. Although the treatment options have increased for some patients, overall progress has been modest. Thus, there is a great need to develop new treatments.

Molecular basis of differentiation therapy for soft tissue sarcomas.

Stem cells are undifferentiated precursor cells with the capacity for proliferation or terminal differentiation. Progression down the differentiation cascade results in a loss of proliferative potential in exchange for the differentiated phenotype. This balance is tightly regulated in the physiologic state.

The use of charge-coupled polymeric microparticles and micromagnets for modulating the bioavailability of orally delivered macromolecules.

Protein drugs have low bioavailability after oral administration, which is due in part to fast transit of the drugs or drug delivery vehicles through the gastrointestinal tract. Increasing the time that the drugs spend in the intestine after dosing would allow for greater absorption and increased bioavailability. We developed a formulation strategy that can be used to prolong intestinal retention of drug delivery vehicles without substantial alterations to current polymeric encapsulation strategies.

Formulation of functionalized PLGA-PEG nanoparticles for in vivo targeted drug delivery.

Nanoparticle (NP) size has been shown to significantly affect the biodistribution of targeted and non-targeted NPs in an organ specific manner. Herein we have developed NPs from carboxy-terminated poly(d,L-lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-b-PEG-COOH) polymer and studied the effects of altering the following formulation parameters on the size of NPs: (1) polymer concentration, (2) drug loading, (3) water miscibility of solvent, and (4) the ratio of water to solvent. We found that NP mean volumetric size correlates linearly with polymer concentration for NPs between 70 and 250 nm in diameter (linear coefficient=0.