Nathan Castro - Academia.edu (original) (raw)

Papers by Nathan Castro

Science & Engineering Faculty, Jun 15, 2014

Science & Engineering Faculty, May 12, 2013

School of Chemistry, Physics & Mechanical Engineering; Science & Engineering Faculty, 2013

2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 2019

Surface brachytherapy is an effective method in the treatment of skin cancer. Current skin brachy... more Surface brachytherapy is an effective method in the treatment of skin cancer. Current skin brachytherapy techniques are based on the placement of a source of gamma or X-ray photons in a close distance from the skin to irradiate the lesion. Due to the nature of photons, radiation dose in these methods may affect healthy tissue as well as sensitive structures around the target. In order to minimize unwarranted and incidental exposure, we propose a new skin brachytherapy applicator based upon beta particles which have penetration ranges of a few millimeters in tissue. The proposed concept is radioactive gel housed within a pre-designed tumor-specific applicator matching the topology of the skin lesion. The particles mixed with the gel showed a uniform distribution pattern, which is an essential prerequisite in having a uniform dose profile on the skin surface. Based on the dose calculation data from the proposed concept, the dose delivered to the depth of 4500 µm in skin tissue is 10% of the dose delivered to the surface of the tumor, making it suitable is treating thin skin tumors especially when located on top of the bone. Through the innovative combination of radioactive gel and tumor-specific applicator, the radiation entering the skin surface can be personalized while minimizing the adverse effects of undesired exposure to the surrounding healthy tissue.

Tissue engineering (TE) has made stark advancements through a greater understanding of the effect... more Tissue engineering (TE) has made stark advancements through a greater understanding of the effects of various biomaterials on cell behavior and mediated tissue formation. Human tissue can be readily classified as a nanocomposite owing to the presence of nanoscale organic and/or inorganic constituents found within the extracellular matrix. Research has begun and continues to leverage this understanding in an effort to fabricate more biomimetic nanobiomaterials, which share similar composition and morphology to native tissue components. In addition, novel three-dimension (3D) scaffold manufacturing techniques are being developed to extend the use of these novel materials toward the development of clinically relevant scaffolds exhibiting not only similar composition, but spatial distribution of tissue-specific extracellular components. Interfacial and complex tissue regeneration applications including those related to osteochondral (bone-cartilage interface) regeneration stand to benef...

Tissue Engineering Part B: Reviews, 2020

Additive Manufacturing, 2019

Limitations for the current clinical treatment strategies for breast reconstruction have prompted... more Limitations for the current clinical treatment strategies for breast reconstruction have prompted researchers and bioengineers to develop unique techniques based on tissue engineering and regenerative medicine (TE&RM) principles. Recently, scaffold-guided soft TE has emerged as a promising approach due to its potential to modulate the process of tissue regeneration. Herein, we utilized additive biomanufacturing (ABM) to develop an original design-based concept for scaffolds which can be applied in TE-based breast reconstruction procedures. The scaffold design addresses biomechanical and biological requirements for medium to large-volume regeneration with the potential of customization. The model is composed of two independent structural components. The external structure provides biomechanical stability to minimize load transduction to the newly formed tissue while the internal structure provides a large pore and fully interconnected pore architecture to facilitate tissue regeneration. A methodology was established to design, optimize and 3D print the external structure with customized biomechanical properties. The internal structure was also designed and printed with a gradient of pore size and a channel structure to facilitate lipoaspirated fat delivery and entrapment. A fused filament fabrication-based printing strategy was employed to print two structures as a monolithic breast implant.

Tissue Engineering Part A, 2017

Adipose-derived stem cells (ADSCs) have the capacity to differentiate into neural precursor cells... more Adipose-derived stem cells (ADSCs) have the capacity to differentiate into neural precursor cells which can be used for nerve regeneration. However, their inherently low neurogenic differentiation ...

Tissue engineering. Part A, 2016

Osseous tissue defects caused by trauma present a common clinical problem. Although traditional c... more Osseous tissue defects caused by trauma present a common clinical problem. Although traditional clinical procedures have been successfully employed, several limitations persist with regards to insufficient donor tissue, disease transmission, and inadequate host-implant integration. Therefore, this work aims to address current limitations regarding inadequate host tissue integration through the use of a novel elastomeric material for three-dimensional (3D) printing biomimetic and bioactive scaffolds. A novel thermoplastic polyurethane-based elastomeric composite filament (Gel-Lay) was used to manufacture porous scaffolds. In an effort to render the scaffolds more bioactive, the flexible scaffolds were subsequently incubated in simulated body fluid at various time points and evaluated for enhanced mechanical properties along with the effects on cell adhesion, proliferation, and 3-week osteogenesis. This work is the first reported use of a novel class of flexible elastomeric materials ...

Nanoscale, Jan 17, 2017

Three-dimensional (3D) functional constructs with biomimetic mechanical and chemical properties a... more Three-dimensional (3D) functional constructs with biomimetic mechanical and chemical properties are ideal for various regenerative medicine applications. These properties of 3D fabricated constructs mainly depend on the intrinsic characteristics of the materials and fabrication method. In this respect, the current use of hydrogels for musculoskeletal tissue repair is not ideal due to the lack of suitable mechanical properties, as well as the high biomimetic requirement for success. To overcome this limitation, we developed a novel functionalized hydrogel with bioactive gold nanoparticles (GNPs), reinforcing a 3D printed microstructure via fused deposition modeling (FDM) for bone tissue regeneration. We used biodegradable thermoplastic polylactic acid (PLA) as the 3D printed microstructure in combination with photo-curable gelatin hydrogels as the encapsulation matrix for the incorporation of cyclic RGD conjugated GNPs (RGNP), and investigated their mechanical properties. In addition...

Scientific reports, Jan 6, 2016

3D printing and ultrasound techniques are showing great promise in the evolution of human musculo... more 3D printing and ultrasound techniques are showing great promise in the evolution of human musculoskeletal tissue repair and regeneration medicine. The uniqueness of the present study was to combine low intensity pulsed ultrasound (LIPUS) and advanced 3D printing techniques to synergistically improve growth and osteogenic differentiation of human mesenchymal stem cells (MSC). Specifically, polyethylene glycol diacrylate bioinks containing cell adhesive Arginine-Glycine-Aspartic acid-Serene (RGDS) peptide and/or nanocrystalline hydroxyapatite (nHA) were used to fabricate 3D scaffolds with different geometric patterns via novel table-top stereolithography 3D printer. The resultant scaffolds provide a highly porous and interconnected 3D environment to support cell proliferation. Scaffolds with small square pores were determined to be the optimal geometric pattern for MSC attachment and growth. The optimal LIPUS working parameters were determined to be 1.5 MHz, 20% duty cycle with 150 mW...

Nanotechnology, 2016

Osteochondral tissue has a complex graded structure where biological, physiological, and mechanic... more Osteochondral tissue has a complex graded structure where biological, physiological, and mechanical properties vary significantly over the full thickness spanning from the subchondral bone region beneath the joint surface to the hyaline cartilage region at the joint surface. This presents a significant challenge for tissue-engineered structures addressing osteochondral defects. Fused deposition modeling (FDM) 3D bioprinters present a unique solution to this problem. The objective of this study is to use FDM-based 3D bioprinting and nanocrystalline hydroxyapatite for improved bone marrow human mesenchymal stem cell (hMSC) adhesion, growth, and osteochondral differentiation. FDM printing parameters can be tuned through computer aided design and computer numerical control software to manipulate scaffold geometries in ways that are beneficial to mechanical performance without hindering cellular behavior. Additionally, the ability to fine-tune 3D printed scaffolds increases further through our investment casting procedure which facilitates the inclusion of nanoparticles with biochemical factors to further elicit desired hMSC differentiation. For this study, FDM was used to print investment-casting molds innovatively designed with varied pore distribution over the full thickness of the scaffold. The mechanical and biological impacts of the varied pore distributions were compared and evaluated to determine the benefits of this physical manipulation. The results indicate that both mechanical properties and cell performance improve in the graded pore structures when compared to homogeneously distributed porous and non-porous structures. Differentiation results indicated successful osteogenic and chondrogenic manipulation in engineered scaffolds.

Neural Engineering, 2016

Nerve regeneration involves a series of complex physiological phenomena. Larger peripheral nerve ... more Nerve regeneration involves a series of complex physiological phenomena. Larger peripheral nerve injuries must be surgically treated, typically with autografts harvested from elsewhere in the body. Central nervous injuries and diseases are more complicated, as there are inhibitive factors resulting in less than ideal repair. Currently, many researches in peripheral nerve regeneration are focused on developing alternatives to the autograft, while efforts for treating central nervous injuries and diseases are devoted to creating a permissive microenvironment for neural regeneration and therapeutic delivery. In recent years, neural tissue engineering has emerged as one of the very promising strategies for treating various nervous system injuries and diseases. Particularly, advancement in both biomaterials and 3D biomimetic scaffolds fabrication techniques such as 3D printing has inspired this field into a new era. This book chapter will focus on the two key pillars and discuss their current progress for improving neural regeneration.

Volume 3: Biomedical and Biotechnology Engineering, 2015

Osteochondral tissue has a graded structure spanning from the subchondral bone region beneath the... more Osteochondral tissue has a graded structure spanning from the subchondral bone region beneath the joint surface to the hyaline cartilage region at the joint surface. Biological, physiological, and mechanical properties over the regions cross-section vary greatly; this provides a significant challenge for tissue-engineered structures addressing osteochondral defects. The objective of this research is to investigate the effects of scaffold pore structure on mechanical, biological, and physiological properties of 3D printed tissue engineered osteochondral scaffolds. Our results indicate that gradient pore structures improve both mechanical properties and cell performance when compared to homogeneously distributed pores and non-porous structures. This study also indicates that including nanocrystalline hydroxyapatite (nHA) into the hydrogel scaffold further improves cellular performance compared to both porous scaffolds without nHA and nonporous scaffolds.Copyright © 2015 by ASME

PLOS ONE, 2015

Articular cartilage is prone to degeneration and possesses extremely poor self-healing capacity d... more Articular cartilage is prone to degeneration and possesses extremely poor self-healing capacity due to inherent low cell density and the absence of a vasculature network. Tissue engineered cartilage scaffolds show promise for cartilage repair. However, there still remains a lack of ideal biomimetic tissue scaffolds which effectively stimulate cartilage regeneration with appropriate functional properties. Therefore, the objective of this study is to develop a novel biomimetic and bioactive electrospun cartilage substitute by integrating cold atmospheric plasma (CAP) treatment with sustained growth factor delivery microspheres. Specifically, CAP was applied to a poly(ε-caprolactone) electrospun scaffold with homogeneously distributed bioactive factors (transforming growth factor-β1 and bovine serum albumin) loaded poly(lactic-co-glycolic) acid microspheres. We have shown that CAP treatment renders electrospun scaffolds more hydrophilic thus facilitating vitronectin adsorption. More importantly, our results demonstrate, for the first time, CAP and microspheres can synergistically enhance stem cell growth as well as improve chondrogenic differentiation of human marrow-derived mesenchymal stem cells (such as increased glycosaminoglycan, type II collagen, and total collagen production). Furthermore, CAP can substantially enhance 3D cell infiltration (over twofold increase in infiltration depth after 1 day of culture) in the scaffolds. By integrating CAP, sustained bioactive factor loaded microspheres, and electrospinning, we have fabricated a promising bioactive scaffold for cartilage regeneration.

Soybean cyst nematode (SCN, Heterodera glycines) represents one of the most serious threats to pr... more Soybean cyst nematode (SCN, Heterodera glycines) represents one of the most serious threats to predictable soybean yield in the United States. Originally discovered in North Carolina during 1954, intraspecific SCN population variability was soon noted. To reduce SCN crop damage, multiple agricul-ture techniques have been exploited. Of these, resistant varieties and rotation to non host crops have been the most effective in reducing the SCN egg population density. However, no single strategy is effective due to variation in SCN populations, lack of complete resistance, and economics of non host crop production. Although it is well accepted that dissimilarities in virulence phenotypes are not associated with any morphological distinctions, knowledge of biochemical characterization of SCN populations is lacking. Therefore, the protein profiles of eggs from four SCN populations were differentiated using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Out of 25 prot...

Cellular and Molecular Bioengineering, 2015

ASME 2013 2nd Global Congress on NanoEngineering for Medicine and Biology, 2013

ABSTRACT Cartilage defects, which are caused by a variety of reasons such as traumatic injuries, ... more ABSTRACT Cartilage defects, which are caused by a variety of reasons such as traumatic injuries, osteoarthritis, or osteoporosis, represent common and severe clinical problems. Each year, over 6 million people visit hospitals in the U.S. for various knee, wrist, and ankle problems. As modern medicine advances, new and novel methodologies have been explored and developed in order to solve and improve current medical problems. One of the areas of investigation that has thus far proven to be very promising is tissue engineering [1, 2]. Since cartilage matrix is nanocomposite, the goal of the current work is to use nanomaterials and nanofabrication methods to create novel biologically inspired tissue engineered cartilage scaffolds for facilitating human bone marrow mesenchymal stem cell (MSC) chondrogenesis. For this purpose, through electrospinning techniques, we designed a series of novel 3D biomimetic nanostructured scaffolds based on carbon nanotubes and biocompatible poly(L-lactic acid) (PLLA) polymers. Specifically, a series of electrospun fibrous PLLA scaffolds with controlled fiber dimension were fabricated in this study. In vitro hMSC studies showed that stem cells prefer to attach in the scaffolds with smaller fiber diameter. More importantly, our in vitro differentiation results demonstrated that incorporation of the biomimetic carbon nanotubes and poly L-lysine coating can induce more chondrogenic differentiations of MSCs than controls, which make them promising for cartilage tissue engineering applications.

Modified Fibers with Medical and Specialty Applications

The adsorbent properties of important wound fluid proteins and cotton cellulose are reviewed. Thi... more The adsorbent properties of important wound fluid proteins and cotton cellulose are reviewed. This review focuses on the adsorption of albumin to cotton-based wound dressings and some chemically modified derivatives targeted for chronic wounds. Adsorption of elastase in the presence of albumin was examined as a model to understand the interactive properties of these wound fluid components with cotton fibers. In the chronic non-healing wound, elastase appears to be over-expressed, and it digests tissue and growth factors, interfering with the normal healing process. Albumin is the most prevalent protein in wound fluid, and in highly to moderately exudative wounds, it may bind significantly to the fibers of wound dressings. Thus, the relative binding properties of both elastase and albumin to wound dressing fibers are of interest in the design of more effective wound dressings. The present work examines the binding of albumin to two different derivatives of cotton, and quantifies the elastase binding to the same derivatives following exposure of albumin to the fiber surface. An HPLC adsorption technique was employed coupled with a colorimetric enzyme assay to quantify the relative binding properties of albumin and elastase to cotton. The results of wound protein binding are discussed in relation to the porosity and surface chemistry interactions of cotton and wound proteins. Studies are directed to understanding the implications of protein adsorption phenomena in terms of fiber-protein models that have implications for rationally designing dressings for chronic wounds.