Browsing by Author "Fernandez-Moure, Joseph S"

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    Biocompatible PLGA-Mesoporous Silicon Microspheres for the Controlled Release of BMP-2 for Bone Augmentation.
    (Pharmaceutics, 2020-02) Minardi, Silvia; Fernandez-Moure, Joseph S; Fan, Dongmei; Murphy, Matthew B; Yazdi, Iman K; Liu, Xuewu; Weiner, Bradley K; Tasciotti, Ennio
    Bone morphogenetic protein-2 (BMP-2) has been demonstrated to be one of the most vital osteogenic factors for bone augmentation. However, its uncontrolled administration has been associated with catastrophic side effects, which compromised its clinical use. To overcome these limitations, we aimed at developing a safer controlled and sustained release of BMP-2, utilizing poly(lactic-co-glycolic acid)-multistage vector composite microspheres (PLGA-MSV). The loading and release of BMP-2 from PLGA-MSV and its osteogenic potential in vitro and in vivo was evaluated. BMP-2 in vitro release kinetics was assessed by ELISA assay. It was found that PLGA-MSV achieved a longer and sustained release of BMP-2. Cell cytotoxicity and differentiation were evaluated in vitro by MTT and alkaline phosphatase (ALP) activity assays, respectively, with rat mesenchymal stem cells. The MTT results confirmed that PLGA-MSVs were not toxic to cells. ALP test demonstrated that the bioactivity of BMP-2 released from the PLGA-MSV was preserved, as it allowed for the osteogenic differentiation of rat mesenchymal stem cells, in vitro. The biocompatible, biodegradable, and osteogenic PLGA-MSVs system could be an ideal candidate for the safe use of BMP-2 in orthopedic tissue engineering applications.
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    Characterization of Mesenchymal Stem Cells from Human Cortical Bone
    (International Journal of Translational Science, 2016) Fernandez-Moure, Joseph S; Corradetti, Bruna; Janecek, Trevor; Eps, Jeffrey Van; Burn, Matthew; Weine, Bradley K; Rameshwar, Pranela; Tasciotti, Ennio
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    Enhanced osteogenic potential of mesenchymal stem cells from cortical bone: a comparative analysis.
    (Stem cell research & therapy, 2015-10) Fernandez-Moure, Joseph S; Corradetti, Bruna; Chan, Paige; Van Eps, Jeffrey L; Janecek, Trevor; Rameshwar, Pranela; Weiner, Bradley K; Tasciotti, Ennio

    Introduction

    Mesenchymal stem cells (MSCs) hold great promise for regenerative therapies in the musculoskeletal system. Although MSCs from bone marrow (BM-MSCs) and adipose tissue (AD-MSCs) have been extensively characterized, there is still debate as to the ideal source of MSCs for tissue-engineering applications in bone repair.

    Methods

    MSCs were isolated from cortical bone fragments (CBF-MSCs) obtained from patients undergoing laminectomy, selected by fluorescence-activated cell sorting analysis, and tested for their potential to undergo mesodermic differentiation. CBF-MSCs were then compared with BM-MSCs and AD-MSCs for their colony-forming unit capability and osteogenic potential in both normoxia and hypoxia. After 2 and 4 weeks in inducing media, differentiation was assessed qualitatively and quantitatively by the evaluation of alkaline phosphatase (ALP) expression and mineral deposition (Von Kossa staining). Transcriptional activity of osteoblastogenesis-associated genes (Alp, RUNX2, Spp1, and Bglap) was also analyzed.

    Results

    The cortical fraction of the bone contains a subset of cells positive for MSC-associated markers and capable of tri-lineage differentiation. The hypoxic conditions were generally more effective in inducing osteogenesis for the three cell lines. However, at 2 and 4 weeks, greater calcium deposition and ALP expression were observed in both hypoxic and normoxic conditions in CBF-MSCs compared with AD- and BM-MSCs. These functional observations were further corroborated by gene expression analysis, which showed a significant upregulation of Bglap, Alp, and Spp1, with a 22.50 (±4.55)-, 46.56 (±7.4)-, 71.46 (±4.16)-fold increase compared with their uninduced counterparts.

    Conclusions

    This novel population of MSCs retains a greater biosynthetic activity in vitro, which was found increased in hypoxic conditions. The present study demonstrates that quantitative differences between MSCs retrieved from bone marrow, adipose, and the cortical portion of the bone with respect to their osteogenic potential exist and suggests the cortical bone as suitable candidate to use for orthopedic tissue engineering and regenerative medicine.
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    Improved Posterolateral Lumbar Spinal Fusion Using a Biomimetic, Nanocomposite Scaffold Augmented by Autologous Platelet-Rich Plasma.
    (Frontiers in bioengineering and biotechnology, 2021-01) Van Eps, Jeffrey L; Fernandez-Moure, Joseph S; Cabrera, Fernando J; Taraballi, Francesca; Paradiso, Francesca; Minardi, Silvia; Wang, Xin; Aghdasi, Bayan; Tasciotti, Ennio; Weiner, Bradley K
    Remodeling of the human bony skeleton is constantly occurring with up to 10% annual bone volume turnover from osteoclastic and osteoblastic activity. A shift toward resorption can result in osteoporosis and pathologic fractures, while a shift toward deposition is required after traumatic, or surgical injury. Spinal fusion represents one such state, requiring a substantial regenerative response to immobilize adjacent vertebrae through bony union. Autologous bone grafts were used extensively prior to the advent of advanced therapeutics incorporating exogenous growth factors and biomaterials. Besides cost constraints, these applications have demonstrated patient safety concerns. This study evaluated the regenerative ability of a nanostructured, magnesium-doped, hydroxyapatite/type I collagen scaffold (MHA/Coll) augmented by autologous platelet-rich plasma (PRP) in an orthotopic model of posterolateral lumbar spinal fusion. After bilateral decortication, rabbits received either the scaffold alone (Group 1) or scaffold with PRP (Group 2) to the anatomic right side. Bone regeneration and fusion success compared to internal control were assessed by DynaCT with 3-D reconstruction at 2, 4, and 6 weeks postoperatively followed by comparative osteogenic gene expression and representative histopathology. Both groups formed significantly more new bone volume than control, and Group 2 subjects produced significantly more trabecular and cortical bone than Group 1 subjects. Successful fusion was seen in one Group 1 animal (12.5%) and 6/8 Group 2 animals (75%). This enhanced effect by autologous PRP treatment appears to occur via astounding upregulation of key osteogenic genes. Both groups demonstrated significant gene upregulation compared to vertebral bone controls for all genes. Group 1 averaged 2.21-fold upregulation of RUNX2 gene, 3.20-fold upregulation of SPARC gene, and 3.67-fold upregulation of SPP1 gene. Depending on anatomical subgroup (cranial, mid, caudal scaffold portions), Group 2 had significantly higher average expression of all genes than both control and Group 1-RUNX2 (8.23-19.74 fold), SPARC (18.67-55.44 fold), and SPP1 (46.09-90.65 fold). Our data collectively demonstrate the osteoinductive nature of a nanostructured MHA/Coll scaffold, a beneficial effect of augmentation with autologous PRP, and an ability to achieve clinical fusion when applied together in an orthotopic model. This has implications both for future study and biomedical innovation of bone-forming therapeutics.
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    Lost in Translation: The Gap in Scientific Advancements and Clinical Application.
    (Frontiers in bioengineering and biotechnology, 2016-01) Fernandez-Moure, Joseph S
    The evolution of medicine and medical technology hinges on the successful translation of basic science research from the bench to clinical implementation at the bedside. Out of the increasing need to facilitate the transfer of scientific knowledge to patients, translational research has emerged. Significant leaps in improving global health, such as antibiotics, vaccinations, and cancer therapies, have all seen successes under this paradigm, yet today, it has become increasingly difficult to realize this ideal scenario. As hospital revenue demand increases, and financial support declines, clinician-protected research time has been limited. Researchers, likewise, have been forced to abandon time- and resource-consuming translational research to focus on publication-generating work to maintain funding and professional advancement. Compared to the surge in scientific innovation and new fields of science, realization of transformational scientific findings in device development and materials sciences has significantly lagged behind. Herein, we describe: how the current scientific paradigm struggles in the new health-care landscape; the obstacles met by translational researchers; and solutions, both public and private, to overcoming those obstacles. We must rethink the old dogma of academia and reinvent the traditional pathways of research in order to truly impact the health-care arena and ultimately those that matter most: the patient.
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    Nanomaterial Nitric Oxide Delivery in Traumatic Orthopedic Regenerative Medicine.
    (Frontiers in bioengineering and biotechnology, 2020-01) Anastasio, Albert Thomas; Paniagua, Ariana; Diamond, Carrie; Ferlauto, Harrison R; Fernandez-Moure, Joseph S
    Achieving bone fracture union after trauma represents a major challenge for the orthopedic surgeon. Fracture non-healing has a multifactorial etiology and there are many risk factors for non-fusion. Environmental factors such as wound contamination, infection, and open fractures can contribute to non-healing, as can patient specific factors such as poor vascular status and improper immunologic response to fracture. Nitric oxide (NO) is a small, neutral, hydrophobic, highly reactive free radical that can diffuse across local cell membranes and exert paracrine functions in the vascular wall. This molecule plays a role in many biologic pathways, and participates in wound healing through decontamination, mediating inflammation, angiogenesis, and tissue remodeling. Additionally, NO is thought to play a role in fighting wound infection by mitigating growth of both Gram negative and Gram positive pathogens. Herein, we discuss recent developments in NO delivery mechanisms and potential implications for patients with bone fractures. NO donors are functional groups that store and release NO, independent of the enzymatic actions of NOS. Donor molecules include organic nitrates/nitrites, metal-NO complexes, and low molecular weight NO donors such as NONOates. Numerous advancements have also been made in developing mechanisms for localized nanomaterial delivery of nitric oxide to bone. NO-releasing aerogels, sol- gel derived nanomaterials, dendrimers, NO-releasing micelles, and core cross linked star (CCS) polymers are all discussed as potential avenues of NO delivery to bone. As a further target for improved fracture healing, 3d bone scaffolds have been developed to include potential for nanoparticulated NO release. These advancements are discussed in detail, and their potential therapeutic advantages are explored. This review aims to provide valuable insight for translational researchers who wish to improve the armamentarium of the feature trauma surgeon through use of NO mediated augmentation of bone healing.
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    Porcine acellular lung matrix for wound healing and abdominal wall reconstruction: A pilot study.
    (Journal of tissue engineering, 2016-01) Fernandez-Moure, Joseph S; Van Eps, Jeffrey L; Rhudy, Jessica R; Cabrera, Fernando J; Acharya, Ghanashyam S; Tasciotti, Ennio; Sakamoto, Jason; Nichols, Joan E
    Surgical wound healing applications require bioprosthetics that promote cellular infiltration and vessel formation, metrics associated with increased mechanical strength and resistance to infection. Porcine acellular lung matrix is a novel tissue scaffold known to promote cell adherence while minimizing inflammatory reactions. In this study, we evaluate the capacity of porcine acellular lung matrix to sustain cellularization and neovascularization in a rat model of subcutaneous implantation and chronic hernia repair. We hypothesize that, compared to human acellular dermal matrix, porcine acellular lung matrix would promote greater cell infiltration and vessel formation. Following pneumonectomy, porcine lungs were processed and characterized histologically and by scanning electron microscopy to demonstrate efficacy of the decellularization. Using a rat model of subcutaneou implantation, porcine acellular lung matrices (n = 8) and human acellular dermal matrices (n = 8) were incubated in vivo for 6 weeks. To evaluate performance under mechanically stressed conditions, porcine acellular lung matrices (n = 7) and human acellular dermal matrices (n = 7) were implanted in a rat model of chronic ventral incisional hernia repair for 6 weeks. After 6 weeks, tissues were evaluated using hematoxylin and eosin and Masson's trichrome staining to quantify cell infiltration and vessel formation. Porcine acellular lung matrices were shown to be successfully decellularized. Following subcutaneous implantation, macroscopic vessel formation was evident. Porcine acellular lung matrices demonstrated sufficient incorporation and showed no evidence of mechanical failure after ventral hernia repair. Porcine acellular lung matrices demonstrated significantly greater cellular density and vessel formation when compared to human acellular dermal matrix. Vessel sizes were similar across all groups. Cell infiltration and vessel formation are well-characterized metrics of incorporation associated with improved surgical outcomes. Porcine acellular lung matrices are a novel class of acellular tissue scaffold. The increased cell and vessel density may promote long-term improved incorporation and mechanical properties. These findings may be due to the native lung scaffold architecture guiding cell migration and vessel formation. Porcine acellular lung matrices represent a new alternative for surgical wound healing applications where increased cell density and vessel formation are sought.
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    Surgical technique for development of a clinically-representative ventral hernia repair infection rat model.
    (MethodsX, 2020-01) Anastasio, Albert Thomas; Van Eps, Jeffrey L; Fernandez-Moure, Joseph S
    The animal model of infection following ventral hernia repair (VHR) has previously been utilized in exploring treatments and innovative therapies, such as implantation of biologic mesh imbedded with various anti-bacterial properties. The rat model has been utilized most commonly, but prior work has failed to recreate an adequately clinically representative model of infection following VHR. Additionally, there is lack of standardization of mesh infection severity across existing literature. Therefore, the aim of this paper is to describe the creation of a clinically representative VHR infection model utilizing an index procedure where a hernia defect is created followed by a VHR using biologic mesh and subsequent infectious agent inoculation. Additionally, we describe the development of a standardization index to quantify severity of mesh infection: the Mesh Infection Severity Index (MISI).•Our protocol involves two procedures, an index procedure where a hernia model is created, and a subsequent procedure where an infectious inoculant is introduced.•We describe the MISI, a standardization tool we hope will allow for ease of cross-institutional data assessment.•In summary, our protocol not only serves as a more clinically representative animal model, but also includes a novel metric to standardize mesh infection severity.