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Sarah E. Stabenfeldt

Bio: Sarah E. Stabenfeldt is an academic researcher from Arizona State University. The author has contributed to research in topics: Traumatic brain injury & Neural stem cell. The author has an hindex of 19, co-authored 52 publications receiving 1238 citations. Previous affiliations of Sarah E. Stabenfeldt include Saint Louis University & Georgia Tech Research Institute.


Papers
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Journal ArticleDOI
TL;DR: This bioadhesive thermoresponsive scaffold may provide a robust delivery vehicle to injured CNS tissue for neural cell transplantation strategies and is developed by tethering laminin-1 (LN) to methylcellulose (MC), a thermore sponsorsive hydrogel.
Abstract: Traumatic injury to the central nervous system (CNS) triggers cell death and deafferentation, which may activate a cascade of cellular and network disturbances. These events often result in the formation of irregularly shaped lesions comprised of necrotic tissue and/or a fluid-filled cavity. Tissue engineering represents a promising treatment strategy for the injured neural tissue. To facilitate minimally invasive delivery of a tissue engineered system, a thermoreversible polymer is an attractive scaffold candidate. We have developed a bioactive scaffold for neural tissue engineering by tethering laminin-1 (LN) to methylcellulose (MC), a thermoresponsive hydrogel. The base MC chain was oxidized via sodium m-periodate to increase MC tethering capacity. Protein immobilization was facilitated by a Schiff base reaction between primary amine groups on LN and the carbonyl groups of the oxidized MC chain. Immunoassays demonstrated tethering of LN at 1.6 +/- 0.5 ng of LN per milligram of MC. Rheological measurements for different MC-LN constructs indicated MC composition- and MC treatment-dependent effects on solution-gelation transition temperature. Cellular assays with primary rat cortical neurons demonstrated enhanced cell adhesion and viability on LN-functionalized MC when compared with base and oxidized MC. This bioadhesive thermoresponsive scaffold may provide a robust delivery vehicle to injured CNS tissue for neural cell transplantation strategies.

199 citations

Journal ArticleDOI
TL;DR: In vitro and in silico analyses demonstrate that PLPs actively collapse fibrin networks, an emergent behaviour that mimics in vivo clot contraction and should inform the future design of a broader class of dynamic, biosynthetic composite materials.
Abstract: Deformable synthetic microgel particles bearing molecular-recognition motifs for fibrin fibres are shown to augment clotting in vitro and mimic in vivo clot contraction, thus recapitulating the functions of natural platelets. Efforts to create platelet-like structures for the augmentation of haemostasis have focused solely on recapitulating aspects of platelet adhesion1; more complex platelet behaviours such as clot contraction2 are assumed to be inaccessible to synthetic systems. Here, we report the creation of fully synthetic platelet-like particles (PLPs) that augment clotting in vitro under physiological flow conditions and achieve wound-triggered haemostasis and decreased bleeding times in vivo in a traumatic injury model. PLPs were synthesized by combining highly deformable microgel particles with molecular-recognition motifs identified through directed evolution. In vitro and in silico analyses demonstrate that PLPs actively collapse fibrin networks, an emergent behaviour that mimics in vivo clot contraction. Mechanistically, clot collapse is intimately linked to the unique deformability and affinity of PLPs for fibrin fibres, as evidenced by dissipative particle dynamics simulations. Our findings should inform the future design of a broader class of dynamic, biosynthetic composite materials.

173 citations

Journal ArticleDOI
TL;DR: The focus of this progress report is to provide a survey of NP strategies employed in cerebral ischemia and brain trauma and provide insights for improved NP‐based diagnostic/treatment approaches.
Abstract: Brain injuries affect a large patient population with major physical and emotional suffering for patients and their relatives; at a significant cost to the society. Effective diagnostic and therapeutic options available for brain injuries are limited by the complex brain injury pathology involving blood–brain barrier (BBB). Brain injuries, including ischemic stroke and brain trauma, initiate BBB opening for a short period of time, which is followed by a second reopening for an extended time. The leaky BBB and/or the alterations in the receptor expression on BBB may provide opportunities for therapeutic delivery via nanoparticles (NPs). The approaches for therapeutic interventions via NP delivery are aimed at salvaging the pericontusional/penumbra area for possible neuroprotection and neurovascular unit preservation. The focus of this progress report is to provide a survey of NP strategies employed in cerebral ischemia and brain trauma and finally provide insights for improved NP-based diagnostic/treatment approaches.

89 citations

Journal ArticleDOI
TL;DR: It is demonstrated that NSC microenvironments modulate cellular activity throughout the neurosphere, contributing to the understanding of ECM-mediated NSC behavior and provide new avenues for developing rationally designed couriers for neurotransplantation.
Abstract: Biomaterial matrices presenting extracellular matrix (ECM) components in a controlled three-dimensional configuration provide a unique system to study neural stem cell (NSC)-ECM interactions. We cultured primary murine neurospheres in a methylcellulose (MC) scaffold functionalized with laminin-1 (MC-x-LN1) and monitored NSC survival, apoptosis, migration, differentiation, and matrix production. Overall, MC-x-LN1 enhanced both NSC survival and maturation compared with MC controls. Significantly lower levels of apoptotic activity were observed in MC-x-LN1 than in MC controls, as measured by bcl-2/bax gene expression and tetramethylrhodamine-dUTP nick end labeling. A higher percentage of NSCs extended neurites in a β₁-integrin-mediated fashion in MC-x-LN1 than in MC controls. Further, the differentiation profiles of NSCs in MC-x-LN1 exhibited higher levels of neuronal and oligodendrocyte precursor markers than in MC controls. LN1 production and co-localization with α₆β₁ integrins was markedly increased within MC-x-LN1, whereas the production of fibronectin was more pronounced in MC controls. These findings demonstrate that NSC microenvironments modulate cellular activity throughout the neurosphere, contributing to our understanding of ECM-mediated NSC behavior and provide new avenues for developing rationally designed couriers for neurotransplantation.

78 citations


Cited by
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Journal ArticleDOI
TL;DR: Various strategies that have been explored to design synthetic hydrogels with extracellular matrix-mimetic bioactive properties, such as cell adhesion, proteolytic degradation and growth factor-binding are addressed.
Abstract: This article summarizes the recent progress in the design and synthesis of hydrogels as tissue-engineering scaffolds. Hydrogels are attractive scaffolding materials owing to their highly swollen network structure, ability to encapsulate cells and bioactive molecules, and efficient mass transfer. Various polymers, including natural, synthetic and natural/synthetic hybrid polymers, have been used to make hydrogels via chemical or physical crosslinking. Recently, bioactive synthetic hydrogels have emerged as promising scaffolds because they can provide molecularly tailored biofunctions and adjustable mechanical properties, as well as an extracellular matrix-like microenvironment for cell growth and tissue formation. This article addresses various strategies that have been explored to design synthetic hydrogels with extracellular matrix-mimetic bioactive properties, such as cell adhesion, proteolytic degradation and growth factor-binding.

1,132 citations

Journal ArticleDOI
TL;DR: The scope of this paper is to review the aqueous polymer solutions that exhibit transition to gel upon temperature change and focuses mainly on hydrogels based on natural polymers as well as poly(ethylene glycol)-biodegradable polyester copolymers.

1,093 citations

Journal ArticleDOI
TL;DR: The development of advanced hydrogel with tunable physiochemical properties is highlighted, with particular emphasis on elastomeric, light‐sensitive, composite, and shape‐memory hydrogels, and a number of potential applications and challenges in the utilization in regenerative medicine are reviewed.
Abstract: Hydrogels are hydrophilic polymer-based materials with high water content and physical characteristics that resemble the native extracellular matrix. Because of their remarkable properties, hydrogel systems are used for a wide range of biomedical applications, such as three-dimensional (3D) matrices for tissue engineering, drug-delivery vehicles, composite biomaterials, and as injectable fillers in minimally invasive surgeries. In addition, the rational design of hydrogels with controlled physical and biological properties can be used to modulate cellular functionality and tissue morphogenesis. Here, the development of advanced hydrogels with tunable physiochemical properties is highlighted, with particular emphasis on elastomeric, light-sensitive, composite, and shape-memory hydrogels. Emerging technologies developed over the past decade to control hydrogel architecture are also discussed and a number of potential applications and challenges in the utilization of hydrogels in regenerative medicine are reviewed. It is anticipated that the continued development of sophisticated hydrogels will result in clinical applications that will improve patient care and quality of life.

1,043 citations

Journal ArticleDOI
03 Aug 2011-Polymers
TL;DR: This review focuses mainly on the studies published over the last 10 years on the synthesis and use of thermoresponsive polymers for biomedical applications including drug delivery, tissue engineering and gene delivery.
Abstract: Thermoresponsive polymers are a class of “smart” materials that have the ability to respond to a change in temperature; a property that makes them useful materials in a wide range of applications and consequently attracts much scientific interest. This review focuses mainly on the studies published over the last 10 years on the synthesis and use of thermoresponsive polymers for biomedical applications including drug delivery, tissue engineering and gene delivery. A summary of the main applications is given following the different studies on thermoresponsive polymers which are categorized based on their 3-dimensional structure; hydrogels, interpenetrating networks, micelles, crosslinked micelles, polymersomes, films and particles.

931 citations

Journal ArticleDOI
TL;DR: An overview of the design of ideal biomimetic porous scaffolds for bone tissue engineering is presented, and concepts and techniques including the production of a hierarchical structure on both the macro- and nano-scales, the adjustment of biomechanical properties through structural alignment and chemical components, and the control of the biodegradability of the scaffold and its by-products are discussed.
Abstract: Increased use of reconstruction procedures in orthopedics, due to trauma, tumor, deformity, degeneration and an aging population, has caused a blossom, not only in surgical advancement, but also in the development of bone implants. Traditional synthetic porous scaffolds are made of metals, polymers, ceramics or even composite biomaterials, in which the design does not consider the native structure and properties of cells and natural tissues. Thus, these synthetic scaffolds often poorly integrate with the cells and surrounding host tissue, thereby resulting in unsatisfactory surgical outcomes due to poor corrosion and wear, mechanical mismatch, unamiable surface environment, and other unfavorable properties. Musculoskeletal tissue reconstruction is the ultimate objective in orthopedic surgery. This objective can be achieved by (i) prosthesis or fixation device implantation, and (ii) tissue engineered bone scaffolds. These devices focus on the design of implants, regardless of the choice of new biomaterials. Indeed, metallic materials, e.g. 316L stainless steel, titanium alloys and cobalt chromium alloys, are predominantly used in bone surgeries, especially in the load-bearing zone of prostheses. The engineered scaffolds take biodegradability, cell biology, biomolecules and material mechanical properties into account, in which these features are ideally suited for bone tissue repair and regeneration. Therefore, the design of the scaffold is extremely important to the success of clinical outcomes in musculoskeletal surgeries. The ideal scaffolds should mimic the natural extracellular matrix (ECM) as much as possible, since the ECM found in natural tissues supports cell attachment, proliferation, and differentiation, indicating that scaffolds should consist of appropriate biochemistry and nano/micro-scale surface topographies, in order to formulate favorable binding sites to actively regulate and control cell and tissue behavior, while interacting with host cells. In addition, scaffolds should also possess a similar macro structure to what is found in natural bone. This feature may provide space for the growth of cells and new tissues, as well as for the carriers of growth factors. Another important concern is the mechanical properties of scaffolds. It has been reported that the mechanical features can significantly influence the osteointegration between implants and surrounding tissues, as well as cell behaviors. Since natural bone exhibits super-elastic biomechanical properties with a Young's modulus value in the range of 1–27 GPa, the ideal scaffolds should mimic strength, stiffness and mechanical behavior, so as to avoid possible post-operation stress shielding effects, which induce bone resorption and consequent implant failure. In addition, the rate of degradation and the by-products of biodegradable materials are also critical in the role of bone regeneration. Indeed, the mechanical integrity of a scaffold will be significantly reduced if the degradation rate is rapid, thereby resulting in a pre-matured collapse of the scaffold before the tissue is regenerated. Another concern is that the by-products upon degradation may alter the tissue microenvironment and then challenge the biocompatibility of the scaffold and the subsequent tissue repair. Therefore, these two factors should be carefully considered when designing new biomaterials for tissue regeneration. To address the aforementioned questions, an overview of the design of ideal biomimetic porous scaffolds is presented in this paper. Hence, a number of original engineering processes and techniques, including the production of a hierarchical structure on both the macro- and nano-scales, the adjustment of biomechanical properties through structural alignment and chemical components, the control of the biodegradability of the scaffold and its by-products, the change of biomimetic surface properties by altering interfacial chemistry, and micro- and nano-topographies will be discussed. In general, the concepts and techniques mentioned above provide insights into designing superior biomimetic scaffolds for bone tissue engineering.

786 citations