Joseph S. Fernandez-Moure

Silicon Micro- and Nanofabrication for Medicine

This manuscript constitutes a review of several innovative biomedical technologies fabricated using the precision and accuracy of silicon micro- and nanofabrication. The technologies to be reviewed are subcutaneous nanochannel drug delivery implants for the continuous tunable zero-order release of therapeutics, multi-stage logic embedded vectors for the targeted systemic distribution of both therapeutic and imaging contrast agents, silicon and porous silicon nanowires for investigating cellular interactions and processes as well as for molecular and drug delivery applications, porous silicon (pSi) as inclusions into biocomposites for tissue engineering, especially as it applies to bone repair and regrowth, and porous silica chips for proteomic profiling. In the case of the biocomposites, the specifically designed pSi inclusions not only add to the structural robustness, but can also promote tissue and bone regrowth, fight infection, and reduce pain by releasing stimulating factors and other therapeutic agents stored within their porous network. The common material thread throughout all of these constructs, silicon and its associated dielectrics (silicon dioxide, silicon nitride, etc.), can be precisely and accurately machined using the same scalable micro- and nanofabrication protocols that are ubiquitous within the semiconductor industry. These techniques lend themselves to the high throughput production of exquisitely defined and monodispersed nanoscale features that should eliminate architectural randomness as a source of experimental variation thereby potentially leading to more rapid clinical translation.

Platelet rich plasma enhances tissue incorporation of biologic mesh

BACKGROUND High recurrence rates because of poor tissue incorporation limit the use of acellular dermal matrices (ADMs) in ventral hernia repair (VHR). Platelet rich plasma (PRP) is a growth factor-rich autologous blood product known to enhance tissue repair through cellular proliferation and neovascularization. We sought to study the effect of PRP on a porcine noncross-linked ADM in an in vivo model of VHR. We hypothesized that PRP would enhance ADM-tissue incorporation in a rat model of VHR. METHODS Whole blood was extracted from Lewis rats followed by PRP isolation and characterization. Using a rat model of VHR, a noncross-linked ADM (Strattice) was implanted and activated PRP applied before closure. Rats were sacrificed at 2, 4, and 6 wk. Immunohistochemical staining of CD 31 on endothelial cells was used to quantify neovascularization. Hematoxylin eosin stained tissues were measured to quantify tissue deposition. RESULTS Platelet concentration of PRP was standardized to 1 × 10(6) platelets/μL. Grossly, vessels were more evident in PRP-treated rats. Immunohistochemical analysis demonstrated neovascularization was significantly greater in the PRP-treated ADMs at all time points. This increase in neovascularization correlated with an increased thickness of tissue deposition at 4 and 6 wk. CONCLUSIONS PRP enhanced neovascularization and incorporation in a rat model of VHR. Enhanced neovascularization was associated with earlier and greater tissue deposition on the ADM. This suggests that PRP could be used as an adjunct to VHR in clinical scenarios where poor wound healing is anticipated and enhanced neovascularization and early tissue deposition are desired.

Lost in Translation: The Gap in Scientific Advancements and Clinical Application

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.

Nanotechnologies and regenerative medical approaches for space and terrestrial medicine.

One purpose of the International Space Station (ISS) is to explore powerful new areas of biomedical science in microgravity. Recent advances in nanotechnology applied to medicine--what we now refer to as nano-medicine--and regenerative medicine have enormous untapped potential for future space and terrestrial medical applications. Novel means for drug delivery and nanoscale screening tools will one day benefit astronauts venturing to Mars and places beyond, while the space laboratory will foster advances in nanotechnologies for diagnostic and therapeutic tools to help our patients here on Earth. Herein we review a series of nanotechnologies and selected regenerative medical approaches and highlight key areas of ongoing and future investigation that will benefit both space and terrestrial medicine. These studies target significant areas of human disease such as osteoporosis, diabetes, radiation injury, and many others.

Nanoantibiotics: a new paradigm for the treatment of surgical infection

Infections following orthopedic device implantations often impose a substantial health burden and result in high medical costs. Currently, preventative methods are often employed following an orthopedic implant to reduce risk of infection; however, contamination of the surgical site can still occur. Although antibiotics have demonstrated a substantial reduction in bacterial growth and maintenance, biofilm formation around the implant can often minimize efficacy of the antibiotic. Recently, nanotechnology has garnered significant interest, resulting in the development of several antibiotic delivery strategies that exhibit extended release and increased efficacy. In this review, treatment methods of orthopedic-device-related infections will be discussed and an overview of antimicrobial-based nanotechnologies will be provided. Specifically, nonmetal-, metal- and oxide-based nanotechnologies, incorporating antibacterial strategies, will be discussed.

Platelet-rich plasma: a biomimetic approach to enhancement of surgical wound healing.

Platelets are small anucleate cytoplasmic cell bodies released by megakaryocytes in response to various physiologic triggers. Traditionally thought to be solely involved in the mechanisms of hemostasis, platelets have gained much attention due to their involvement wound healing, immunomodulation, and antiseptic properties. As the field of surgery continues to evolve so does the need for therapies to aid in treating the increasingly complex patients seen. With over 14 million obstetric, musculoskeletal, and urological and gastrointestinal surgeries performed annually, the healing of surgical wounds continues to be of upmost importance to the surgeon and patient. Platelet-rich plasma, or platelet concentrate, has emerged as a possible adjuvant therapy to aid in the healing of surgical wounds and injuries. In this review, we will discuss the wound healing properties of platelet-rich plasma and various surgical applications.

Porcine acellular lung matrix for wound healing and abdominal wall reconstruction: A pilot study

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.

Novel therapeutic strategies for degenerative disc disease: Review of cell biology and intervertebral disc cell therapy:

Intervertebral disc degeneration is a disease of the discs connecting adjoining vertebrae in which structural damage leads to loss of disc integrity. Degeneration of the disc can be a normal process of ageing, but can also be precipitated by other factors. Literature has made substantial progress in understanding the biological basis of intervertebral disc, which is reviewed here. Current medical and surgical management strategies have shortcomings that do not lend promise to be effective solutions in the coming years. With advances in understanding the cell biology and characteristics of the intervertebral disc at the molecular and cellular level that have been made, alternative strategies for addressing disc pathology can be discovered. A brief overview of the anatomic, cellular, and molecular structure of the intervertebral disc is provided as well as cellular and molecular pathophysiology surrounding intervertebral disc degeneration. Potential therapeutic strategies involving stem cell, protein, and genetic therapy for intervertebral disc degeneration are further discussed.

Cross-linking of porcine acellular dermal matrices negatively affects induced neovessel formation using platelet-rich plasma in a rat model of hernia repair

The degree of cross‐linking within acellular dermal matrices (ADM) seems to correlate to neovascularization when used in ventral hernia repair (VHR). Platelet‐rich plasma (PRP) enhances wound healing through several mechanisms including neovascularization, but research regarding its effect on soft tissue healing in VHR is lacking. We sought to study the effect of cross‐linking on PRP‐induced neovascularization in a rodent model of bridging VHR. We hypothesized that ADM cross‐linking would negatively affect PRP‐induced neovessel formation. PRP was extracted and characterized from pooled whole blood. Porcine cross‐linked (cADM) and non–cross‐linked ADMs (ncADM) were implanted in a rat model of chronic VHR after treatment with saline (control) or PRP. Neovascularization of samples at 2, 4, and 6 weeks was assessed by hematoxylin and eosin and immunohistochemical staining of CD 31. Adhesion severity at necropsy was compared using a previously validated scale. Addition of PRP increased neovascularization in both cADM and ncADM at 2‐ and 4‐week time points but appeared to do so in a dependent fashion, with significantly greater neovascularization in the PRP‐treated ncADMs compared to cADMs. Omental adhesions were increased in all PRP‐treated groups. Results indicate that, for 2‐week measurements when compared with the cADM group without PRP therapy, the mean change in neovascularization due to ncADM was 3.27 (Z = 2.75, p = 0.006), PRP was 17.56 (Z = 14.77, p < 0.001), and the combined effect of ncADM and PRP was 9.41 (Z = 5.6, p < 0.001). The 4‐week data indicate that the average neovascularization change due to ncADM was 0.676 (Z = 0.7, p = 0.484), PRP was 7.69 (Z = 7.95, p < 0.001), and combined effect of ncADM and PRP was 5.28 (Z = 3.86, p < 0.001). These findings validate PRP as a clinical adjunct to enhance the native tissue response to implantable biomaterials and suggest that ncADM is more amenable than cADM to induced neovascularization. PRP use could be advantageous in patients undergoing VHR where poor incorporation is anticipated and early‐enhanced neovascularization is desired.

Case report on the non-operative management of a retrievable inferior vena cava filter perforating the duodenum

Highlights • IVC filters as an alternative to anticoagulation therapy carry their own risks.• IVC filters may erode into surrounding structures.• Duodenal perforation by a retrievable IVC filter is a rare and serious complication.• Caval enteric perforation by retrievable IVC filter can be managed non-operatively.