Melissa Krebs

Melissa Krebs
Colorado School of Mines · Department of Chemical and Biological Engineering

Ph.D.

About

56
Publications
7,449
Reads
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2,400
Citations
Additional affiliations
August 2012 - present
Colorado School of Mines
Position
  • Professor (Assistant)
June 2011 - July 2012
Case Western Reserve University
Position
  • Research Assistant Professor
June 2011 - July 2012
University of Colorado Hospital
Position
  • Visiting Scientist

Publications

Publications (56)
Article
The field of biomaterials aims to improve regenerative outcomes or scientific understanding for a wide range of tissue types and ailments. Biomaterials can be fabricated from natural or synthetic sources and display a plethora of mechanical, electrical, and geometrical properties dependent on their desired application. To date, most biomaterial sys...
Article
Hydrogels are three-dimensional networks of hydrophilic polymers that have garnered significant attention as wound-healing materials. Many synthetic hydrogels are fabricated using a radical polymerization approach that requires an initiator molecule that is often photo- or thermosensitive. Initiator-free hydrogels are an emerging area of research t...
Article
Glaucoma is a multifactorial progressive optic neuropathy characterized by the loss of retinal ganglion cells leading to irreversible blindness. It is the leading cause of global irreversible blindness and is currently affecting over 70 million people. Elevated intraocular pressure (IOP) is considered the only modifiable risk factor and is a target...
Article
The growth plate is a complex cartilage structure in long bones that mediates growth in children. When injured, the formation of a “bony bar” can occur which impedes normal growth and can cause angular deformities or growth arrest. Current treatments for growth plate injuries are limited and result in poor patient outcomes, necessitating research t...
Article
Dental cavities are the most prevalent, preventable disease worldwide providing a need for robust treatment options to restore both the form and function of decaying teeth. Here is a presentation of a possible regenerative pulp capping agent that can serve to restore tooth function while regenerating healthy dentin tissue over a long period of time...
Article
The growth plate is a cartilage tissue near the ends of children’s long bones and is responsible for bone growth. Injury to the growth plate can result in the formation of a ‘bony bar’ which can span the growth plate and result in bone growth abnormalities in children. Biomaterials such as chitosan microgels could be a potential treatment for growt...
Article
Full-text available
Physeal injuries can result in the formation of a “bony bar” which can lead to bone growth arrest and deformities in children. Vascular endothelial growth factor (VEGF) has been shown to play a role in bony bar formation, making it a potential target to inhibit bony repair tissue after physeal injury. The goal of this study was to investigate wheth...
Article
Glaucoma is a degenerative eye disease in which damage to the optic nerve leads to a characteristic loss of vision. The primary risk factor for glaucoma is increased intraocular pressure which is caused by an imbalance of aqueous humor generation and subsequent drainage through the trabecular meshwork (TM) drainage system. The small size, donor tis...
Article
The absence of quantitative in vitro cell–extracellular matrix models represents an important bottleneck for basic research and human health. Randomness of cellular distributions provides an opportunity for the development of a quantitative in vitro model. However, quantification of the randomness of random cell distributions is still lacking. In t...
Article
Biopolymer microgels are emerging as a versatile tool for aiding in the regeneration of damaged tissues due to their biocompatible nature, tunable microporous structure, ability to encapsulate bioactive factors, and tailorable properties such as stiffness and composition. These properties of microgels, along with their injectability, have allowed f...
Article
Full-text available
Correction for ‘Sustained delivery of anti-VEGF from injectable hydrogel systems provides a prolonged decrease of endothelial cell proliferation and angiogenesis in vitro ’ by Nathan A. Fletcher et al. , RSC Adv. , 2018, 8 , 8999–9005.
Article
Full-text available
Therapeutic antibodies are attractive treatment options for numerous diseases based on their ability to target and bind to specific proteins or antigens. Bevacizumab, an antiangiogenic antibody, has shown promise for multiple diseases, including various cancers and macular degeneration, where excessive VEGF secretion induces aberrant angiogenesis....
Preprint
The absence of quantitative in vitro cell-extracellular matrix models represents an important bottleneck for basic research and human health. Randomness of cellular distributions provides an opportunity for the development of a quantitative in vitro model. However, quantification of the randomness of random cell distributions is still lacking. In t...
Article
The physis, or growth plate, is a cartilaginous region at the end of children's long bones that serves as the primary center for longitudinal growth and characterizes the immature skeleton. Musculoskeletal injury including fracture, infection, malignancy, or iatrogenic damage has risk of physeal damage. Physeal injuries account for 30% of pediatric...
Article
This work investigates techniques to produce biocompatible hydrogels with tunable stiffness without the addition of crosslinking agents or altering cell binding sites. Alginate and water-soluble chitosan salts were used to form polyelectrolyte complexes (PECs), where the storage and loss moduli could be increased by raising gelation temperatures. T...
Article
Full-text available
A third of all pediatric fractures involve the growth plate and can result in impaired bone growth. The growth plate (or physis) is cartilage tissue found at the end of all long bones in children that is responsible for longitudinal bone growth. Once damaged, cartilage tissue within the growth plate can undergo premature ossification and lead to un...
Article
Biomaterial controlled osteoinduction is influenced by the porous microenvironment and the composition of incorporated calcium orthophosphate (CaPi) polymorphs, however for the design of materials that rival the efficacies of natural grafts a systematic approach to assessing the physicochemical properties that affects cellular differentiation is ne...
Article
Inspired by natural mineralization processes, here we present the stepwise mineralization of hydrogels with synthetic control over the amount of deposited CaPi and selective tuning of the coating composition. Alternate immersion of the hydrogel at 3 minute intervals in calcium salt (Ca2+) and inorganic phosphate (Pi) solutions under mild aqueous co...
Article
Glaucoma is a disease in which damage to the optic nerve leads to progressive, irreversible vision loss. The intraocular pressure (IOP) is the only modifiable risk factor for glaucoma and its lowering is considered a useful strategy for preventing or slowing down the progression of glaucomatous neuropathy. Elevated intraocular pressure associated w...
Article
Full-text available
Purpose: This study aims to develop biodegradable and biocompatible polymer-based nanofibers that continuously monitor pH within microenvironments of cultured cells in real-time. In the future, these fibers will provide a scaffold for tissue growth while simultaneously monitoring the extracellular environment. Methods: Sensors to monitor pH were...
Article
In this work, an emulsion crosslinking method was developed to produce chitosan-genipin microgels which acted as an injectable and microporous scaffold. Chitosan was characterized with respect to pH by light scattering and aqueous titration. Microgels were characterized with swelling, light scattering, and rheometry of densely-packed microgel solut...
Article
There has been much work examining bioinspired mineralization of polymeric hydrogels with calcium phosphates, yet a systematic method for the predictable and tunable synthesis of biomimetic apatites is yet to be developed. Here, a method for the selective mineralization of substituted apatite composite hydrogels where the incorporated mineral phase...
Article
This work reports the preparation of zwitterionic cryogels for the sustained release of proteins for up to 4 months. In addition, high protein loading efficiency of up to 80% was achieved. Control studies with different hydrogels (such as non-ionic cryogels and non-ionic and zwitterionic gels prepared at room temperature) were performed to understa...
Article
Therapeutic antibodies are currently used for the treatment of various diseases, but large doses delivered systemically are typically required. Localized controlled delivery techniques would afford major benefits such as decreasing side effects and required doses. Injectable biopolymer systems are an attractive solution due to their minimally invas...
Article
Full-text available
Fiber alignment is the defining architectural characteristic of discontinuous fiber composites and is dictated by shear-dominated processing techniques including flow-injection molding, tape-casting, and mold-casting. However, recent colloidal assembly techniques have started to employ additional forces in fiber suspensions that have the potential...
Article
Full-text available
We have developed a mathematical model that allows simulation of oxygen distribution in a bone defect as a tool to explore the likely effects of local changes in cell concentration, defect size or geometry, local oxygen delivery with oxygen-generating biomaterials (OGBs), and changes in the rate of oxygen consumption by cells within a defect. Exper...
Article
Stem cells, such as mesenchymal stem cells (MSCs), contribute to bone fracture repair if they are delivered to the injury site. However, it is difficult to assess the retention and differentiation of these cells after implantation. Current options for non-invasively tracking the transplanted stem cells are limited. Cell-based therapies using MSCs w...
Article
Full-text available
Nanofibrous scaffolds are of interest in tissue engineering due to their high surface area to volume ratio, interconnected pores, and architectural similarity to the native extracellular matrix. Our laboratory recently developed a biodegradable, photo-crosslinkable alginate biopolymer. Here, we show the capacity of the material to be electrospun in...
Article
The formation of 3D electrospun mat structures from alginate-polyethylene oxide (PEO) solution blends is reported. These unique architectures expand the capabilities of traditional electrospun mats for applications such as regenerative medicine, where a scaffold can help to promote tissue growth in three dimensions. The mat structures extend off th...
Article
Photocrosslinkable biomaterials are promising for tissue engineering applications due to their capacity to be injected and form hydrogels in situ in a minimally invasive manner. Our group recently reported on the development of photocrosslinked alginate hydrogels with controlled biodegradation rates, mechanical properties, and cell adhesive propert...
Article
Biodegradable poly(lactic-co-glycolic acid) (PLGA) scaffolds are widely used for the delivery of therapeutic molecules such as plasmid DNA (pDNA) and growth factors. However, many of these scaffolds must be implanted, and it would be beneficial to develop PGLA systems that can be injected in a minimally invasive manner. In this study, we present an...
Article
We report here preparation of nanofibers containing alginate using two different molecular weights (MWs): 37kDa and 196kDa. Low MW alginates are attractive for in vivo tissue scaffolds where degradation and clearance from the body are desirable, whereas higher MW alginates are amenable for topical use as wound coverage because of its better mechani...
Article
Short interfering RNA (siRNA) functions directly in the cytoplasm, where it is assembled into an RNA-induced silencing complex (RISC). The localized delivery of siRNA to a specific site in vivo is highly challenging. There are many disease states in which a systemic effect of RNAi may be desirable; some examples include non-localized cancers, HIV,...
Article
Full-text available
Electrospun natural biopolymers are of great interest in the field of regenerative medicine due to their unique structure, biocompatibility, and potential to support controlled release of bioactive agents and/or the growth of cells near a site of interest. The ability to electrospin chitosan and alginate to form polyionic complexed nanofibrous scaf...
Article
Alginate, a natural polysaccharide that has shown great potential as a cell scaffold for the regeneration of many tissues, has only been nominally explored as an electrospun biomaterial due to cytotoxic chemicals that have typically been used during nanofiber formation and crosslinking. Alginate cannot be electrospun by itself and is often co‐spun...
Article
Full-text available
Aggregation in nondiffusion limited colloidal particle suspensions follows a temporal power-law dependence that is consistent with classical diffusion limited cluster aggregation models; however, the dynamic scaling exponents observed in these systems are not adequately described by diffusion limited cluster aggregation models, which expect these s...
Article
Full-text available
The ability to silence the expression of specific genes at a particular location of the body would provide a powerful new therapeutic tool for treatment of diseases such as cancer or for use in regenerative medicine. RNA interference (RNAi) is a gene silencing mechanism where specific mRNA molecules that are complementary to short interfering RNA (...
Article
Appropriate porosity is an important biomaterial design criterion for scaffolds used in tissue engineering applications as it can permit increased cell adhesion, migration, proliferation and extracellular matrix production within the scaffold at a tissue defect site. Tissue engineering scaffolds can either be injected in a minimally invasive manner...
Article
The creation of ordered cellular structures is important for tissue engineering research. Here, we present a novel strategy for the assembly of cells into linear arrangements by negative magnetophoresis using inert, cytocompatible magnetic nanoparticles. In this approach, magnetic nanoparticles dictate the cellular assembly without relying on cell...
Article
There is a significant need for improved therapy for bone regeneration. The delivery of recombinant bone morphogenetic proteins has been approved for clinical use to promote osteogenesis, but still has limitations such as expense, degradation of the proteins in vivo and difficulties retaining protein at the site of injury. Localized gene delivery i...
Article
Alignment of data is critical for analysis involving the comparison of multiple files. Analytical sensor data resulting from complex chemical mixtures can often be mis-aligned due to time-varying biases resulting from mechanical instrument variability. In addition to the necessity for time alignment, data from the micromachined differential mobilit...
Article
There is an urgent need for a small, inexpensive sensor that can rapidly detect bio-warfare agents with high specificity. Bacillus anthracis, the causative agent of anthrax, would be a perilous disease-causing organism in the event of a release. Currently, most anthrax detection research is based on nucleic acid detection, immunoassays and mass spe...
Article
Analyzing the response of analytical sensors to complex chemical mixtures is difficult, as signals may overlap and may vary between experiments. The analysis and comparison of data files depends on their repeatability, and misaligned signals will not be directly comparable. We present a method for aligning chromatographic data by the selection of l...
Article
As bacteria grow and proliferate, they release a variety of volatile compounds that can be profiled and used for speciation, providing an approach amenable to disease diagnosis through quick analysis of clinical cultures as well as patient breath analysis. As a practical alternative to mass spectrometry detection and whole cell pyrolysis approaches...
Article
Full-text available
With international concern growing over the potential for chemical and biological terrorism, there is an urgent need for a sensor that can quickly and accurately detect chemical and biological agents. Such a sensor needs to be portable, robust, and sensitive, with fast sample analysis time. We will demonstrate the use of a micromachined differentia...
Article
Full-text available
The analysis of chromatographic data resulting from complex chemical mixtures is challenging. Components may co-elute, causing their signals to overlap. An algorithm that will increase the signal-to-noise ratio so compounds present in low abundance can be better distinguished from noise is useful in this type of analysis. The autoregressive (AR) fi...

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