[Show abstract][Hide abstract] ABSTRACT: Electrospinning of water-soluble polymers and retaining their mechanical strength and bioactivity remain challenging. Volatile organic solvent soluble polymers and their derivatives are preferred for fabricating electrospun nanofibers. We report the synthesis and characterization of
2-nitrobenzyl-gelatin (N-Gelatin) - a novel gelatin Schiff base derivative - and the resulting electrospun nanofiber matrices. The 2-nitrobenzyl group is a photoactivatable-caged compound and can be cleaved from the gelatin nanofiber matrices following UV exposure. Such hydrophobic modification
allowed the fabrication of gelatin and blend nanofibers with poly(caprolactone) (PCL) having significantly improved tensile properties. Neat gelatin and their PCL blend nanofiber matrices showed a modulus of 9.08±1.5 MPa and 27.61±4.3 MPa, respectively while the modified gelatin
and their blends showed 15.63±2.8 MPa and 24.47±8.7 MPa, respectively. The characteristic infrared spectroscopy band for gelatin Schiff base derivative at 1560 cm–1 disappeared following exposure to UV light indicating the regeneration of free NH2
group and gelatin. These nanofiber matrices supported cell attachment and proliferation with a well spread morphology as evidenced through cell proliferation assay and microscopic techniques. Modified gelatin fiber matrices showed a 73% enhanced cell attachment and proliferation rate compared
to pure gelatin. This polymer modification methodology may offer a promising way to fabricate electrospun nanofiber matrices using a variety of proteins and peptides without loss of bioactivity and mechanical strength.
No preview · Article · Oct 2015 · Journal of Biomedical Nanotechnology
[Show abstract][Hide abstract] ABSTRACT: Amputations of the upper extremity are severely debilitating, current treatments support very basic limb movement, and patients undergo extensive physiotherapy and psychological counseling. There is no prosthesis that allows the amputees near normal function. With increasing number of amputees due to injuries sustained in accidents, natural calamities, and international conflicts, there is a growing requirement for novel strategies and new discoveries. Advances have been made in technological, material, and in prosthesis integration where researchers are now exploring artificial prosthesis that integrate with the residual tissues and function based on signal impulses received from the residual nerves. Efforts are focused on challenging experts in different disciplines to integrate ideas and technologies to allow for the regeneration of injured tissues, recording on tissue signals and feedback to facilitate responsive movements and gradations of muscle force. A fully functional replacement and regenerative or integrated prosthesis will rely on interface of biological process with robotic systems to allow individual control of movement such as at the elbow, forearm, digits, and thumb in the upper extremity. Regenerative engineering focused on the regeneration of complex tissue and organ systems will be realized by the cross-fertilization of advances over the past 30 years in the fields of tissue engineering, nanotechnology, stem cell science, and developmental biology. The convergence of toolboxes crated within each discipline will allow interdisciplinary teams from engineering, science, and medicine to realize new strategies, mergers of disparate technologies, such as biophysics, smart bionics, and the healing power of the mind. Tackling the clinical challenges, interfacing the biological process with bionic technologies, engineering biological control of the electronic systems, and feedback will be the important goals in regenerative engineering over the next two decades.
[Show abstract][Hide abstract] ABSTRACT: Playing the role as the largest organ in the body, the skin serves as a protective shield. Since the 1860s when combating dermal wounds, many options have been addressed to assist in the healing process. Current limitations with existing treatments, such as autographs and allographs have propelled research towards tissue engineering for skin tissue regeneration. Tissue-engineering techniques bring advancement in the treatment of acute and chronic wounds through the use of stem cells, biomaterials, and biological factors. Strategies for skin tissue engineering involve emulating the physical and biochemical environment of native tissue through the use of a synthetic extracellular matrix or scaffold. The scaffold provides an initial substrate for cell attachment and serves as a wound dressing to combat infection. Material selection and choice of fabrication technique play a role in the chemical and topographical make-up of the scaffold, which ultimately affect cell behavior. The present review elaborates on the types of stem cells used for skin tissue engineering, discusses natural and synthetic polymers used to create scaffolds, and highlights the relevance of electrospun nanofibers in providing nanotopographical cues and bioactivity.
[Show abstract][Hide abstract] ABSTRACT: Polyphosphazenes consist of an inorganic backbone of alternating phosphorous and nitrogen atoms form a unique class of synthetic materials with vast potential for biomedical applications. Through studies conducted by our group and other researchers, one can effectively control polymer properties by modulating the side group chemistry. This approach has enabled the generation of a biomaterial library detailing tunable physical, chemical, and biological properties. Biodegradable polyphosphazenes undergo controlled degradation producing nontoxic and neutral pH degradation products. These polymers have excellent buffering capacity due to the simultaneous production of phosphates and ammonia during polyphosphazene degradation. This chapter focuses on the synthesis of biodegradable polyphosphazenes, their degradation characteristics, their biocompatibility, and their application for tissue regeneration and as drug delivery matrices.
[Show abstract][Hide abstract] ABSTRACT: Regenerative engineering was conceptualized by bridging the lessons learned in developmental biology and stem cell science with biomaterial constructs and engineering principles to ultimately generate de novo tissue. We seek to incorporate our understanding of natural tissue development to design tissue-inducing biomaterials, structures and composites than can stimulate the regeneration of complex tissues, organs, and organ systems through location-specific topographies and physico-chemical cues incorporated into a continuous phase. This combination of classical top-down tissue engineering approach with bottom-up strategies used in regenerative biology represents a new multidisciplinary paradigm. Advanced surface topographies and material scales are used to control cell fate and the consequent regenerative capacity.Musculoskeletal tissues are critical to the normal functioning of an individual and following damage or degeneration they show extremely limited endogenous regenerative capacity. The increasing demand for biologically compatible donor tissue and organ transplants far outstrips the availability leading to an acute shortage. We have developed several biomimetic structures using various biomaterial platforms to combine optimal mechanical properties, porosity, bioactivity, and functionality to effect repair and regeneration of hard tissues such as bone, and soft tissues such as ligament and tendon. Starting with simple structures, we have developed composite and multi-scale systems that very closely mimic the native tissue architecture and material composition. Ultimately, we aim to modulate the regenerative potential, including proliferation, phenotype maturation, matrix production, and apoptosis through cell-scaffold and host –scaffold interactions developing complex tissues and organ systems.
No preview · Article · Nov 2014 · MRS Online Proceeding Library
[Show abstract][Hide abstract] ABSTRACT: Current treatment options for tissue loss or organ failure include organ/tissue transplantation of autografts/allografts, delivery of bioactive agents, and utilization of synthetic replacements composed of metals, polymers, and ceramics. However each strategy suffers from a number of limitations. The early attempts to overcome these drawbacks led to the emergence of tissue engineering that provided viable tissue substitutes using a combination of biomaterials, cells, and factors. This approach was ideally suited to repair damaged tissues; however the substitution and regeneration of large tissue volumes and multi-level tissues such as complex organ systems require more than optimal combinations of biomaterials and biologics.‘Regenerative Engineering’ is aimed at creating large and complex tissue systems incorporating advances in material science, stem cell technology and developmental biology. We believe that recent breakthrough technologies in advanced materials science and nanotechnology allow us to recapitulate native tissues. The novel designer polymers incorporate bioactivity and physical features specific to a regeneration application. Overall, engineered materials and scaffolds afford selective control of cell sensitivity, and precise control of temporal and spatial stimulatory cues. We aim to build multi-level systems such as organs through location-specific topographies and physico-chemical cues incorporated into a continuous phase using a combination of classical top-down tissue engineering approach with bottom-up strategies used in regenerative biology.Musculoskeletal tissues are critical to the normal functioning of an individual and following damage or degeneration show extremely limited endogenous regenerative capacity. The development of material and structural platforms to modulate stem cell behavior to enhance regeneration is an area of great interest. In this manuscript we cover some examples of material development, and incorporation of topographical and cytokine cues to modulate the differentiation of hard and soft musculoskeletal tissues such as bone, ligament and tendon.
No preview · Article · Aug 2014 · MRS Online Proceeding Library
[Show abstract][Hide abstract] ABSTRACT: Musculoskeletal tissues are critical to the normal functioning of an individual and following damage or degeneration they show extremely limited endogenous regenerative capacity. The future of regenerative medicine is the combination of advanced biomaterials, structures, and cues to re-engineer/guide stem cells to yield the desired organ cells and tissues. Tissue engineering strategies were ideally suited to repair damaged tissues; however, the substitution and regeneration of large tissue volumes and multi-level tissues such as complex organ systems integrated into a single phase require more than optimal combinations of biomaterials and biologics. We highlight bioinspired advancements leading to novel regenerative scaffolds especially for musculoskeletal tissue repair and regeneration. Tissue and organ regeneration relies on the spatial and temporal control of biophysical and biochemical cues, including soluble molecules, cell-cell contacts, cell-extracellular matrix contacts, and physical forces. Strategies that recapitulate the complexity of the local microenvironment of the tissue and the stem cell niche play a crucial role in regulating cell self-renewal and differentiation. Biomaterials and scaffolds based on biomimicry of the native tissue will enable convergence of the advances in materials science, the advances in stem cell science, and our understanding of developmental biology.
[Show abstract][Hide abstract] ABSTRACT: The electrospinning of chitosan remains challenging due to its rigid crystalline structure,
insufficient viscosity and limited solubility in common organic solvents. This work
presents a “smart” chitosan modification that allows electrospinning irrespective of
molecular weight or deacetylation value and without blending with synthetic polymers. A
novel derivative, namely 2-nitrobenzyl-chitosan (NB), at various molar compositions of
chitosan:2-nitrobenzaldehyde (1:1 (NB-1), 1:0.5 (NB-2), 1:0.25 (NB-3)) was synthesized
by the reaction between amino groups of chitosan and aldehyde groups of 2-
Full-text · Article · May 2014 · Polymers for Advanced Technologies
[Show abstract][Hide abstract] ABSTRACT: Current strategies to treat tissue or organ failure rely heavily on autografts and allografts. There has been some success; however, both approaches have limitations, including donor organ shortage, risk of disease transmission, and immune rejection. The future of regenerative medicine is the combination of advanced biomaterials, structures, and cues to guide stem cells to differentiate into the desired tissues. Strategies that recapitulate the complexity of the local tissue microenvironment and the stem cell niche play a crucial role in regulating cell self-renewal and differentiation. Biomaterials and scaffolds based on biomimicry of the native tissue will enable a convergence of concepts derived from advanced materials science, stem cell science, and developmental biology. Academic institutions take up the burden of implementing innovative initiatives through research grants provided by federal agencies and private foundations. Transitioning laboratory research into commercial reality requires a realization of the business opportunity, market share, prototyping, and market valued data sets. Funding initiatives by the National Science Foundation have helped to accelerate technology transfer in partnership with industries. Opportunities to partner with medical device companies and contract service providers must be leveraged to collectively prepare a business roadmap leading to a successful startup.
[Show abstract][Hide abstract] ABSTRACT: Electrospun nanofiber matrices have been produced using natural and synthetic polymers for a variety of biomedical applications. However, electrospinning of water-soluble polymers still remains as a major challenge. Polysaccharides are difficult to spin and often mixed with other synthetic polymers to produce electrospun nanofiber matrices. Chitosan, the deacetylated form of chitin, is reported to be a biocompatible, biodegradable, antimicrobial and non-toxic polysaccharide and thus used for a variety of biomedical applications including tissue engineering, drug delivery device and wound healing. Chitosan electrospinning remains challenging due to limited solubility and a rigid crystalline structure which does not allow sufficient polymer concentrations required for successful fiber formation by electrospinning. Here we present a novel and “smart” chitosan modification methodology that allows direct electrospinning of high molecular weight chitosan at very high concentrations. In brief, to facilitate chitosan electrospinning a new 2-nitrobenzyl-chitosan derivative was synthesized and electrospun nanofibers were produced by dissolving the derivative in trifluoroacetic acid (TFA) solvent. In this derivative, 2-nitrobenzyl aldehyde is used as a photolytic removal group to block the amino groups of chitosan and subsequently reduce its structural rigidity. Subsequently, the electrospun nanofiber matrices produced by 2-nitrobenzyl-chitosan was exposed to UV light to produce pure chitosan nanofiber matrix. Electrospinning parameters were optimized to produce defect-free cylindrical nanofibers at 15% (wt/v) chitosan solution concentration and 1 kV/cm electrical potential. In this work we report on electrospinning of three different 2-Nitrobenzyl-chitosan compositions namely 1:1, 1:0.5, and 1:0.25 and evaluating chitosan matrices for scaffold properties and cell compatibility. The mechanism of photolysis to obtain neat chitosan from 2-Nitrobenzyl-chitosan followed by UV exposure was confirmed by FTIR analysis. The morphology of the electrospun fibers, pore structure, and fiber diameter was examined using scanning electron microscopy. Biocompatibility was evaluated by measuring cell proliferation and metabolic activity of MC3T3 cells seeded onto the nanofiber scaffolds.The samples were screened for antimicrobial activity by disc diffusion method using B. subtilis as gram positive, E. coli as gram negative, C. albicans as yeast and A. niger as fungi. The results showed that the samples have a strong inhibitory activity against all pathogenic microorganisms used.
[Show abstract][Hide abstract] ABSTRACT: Repair and regeneration of human tissues and organs using biomaterials, cells and/or growth factors is the ultimate goal of tissue engineers. One of the grand challenges in this field is to closely mimic the structures and properties of native tissues. Regenerative engineering-the convergence of tissue engineering with advanced materials science, stem cell science, and developmental biology-represents the next valuable tool to overcome the challenges. This article reviews the recent progress in developing advanced chitosan structures using various fabrication techniques. These chitosan structures, together with stem cells and functional biomolecules, may provide a robust platform to gain insight into cell-biomaterial interactions and may function as excellent artificial extracellular matrices to regenerate complex human tissues and biological systems.
No preview · Article · Jul 2013 · Acta biomaterialia
[Show abstract][Hide abstract] ABSTRACT: Scaffold based bone tissue engineering (BTE) has made great progress in regenerating lost bone tissue. Materials of natural and synthetic origin have been used for scaffold fabrication. Scaffolds derived from natural polymers offer greater bioactivity and biocompatibility with mammalian tissues to favor tissue healing, due to their similarity to native extracellular matrix (ECM) components. Often it is a challenge to fabricate natural polymer based scaffolds for BTE applications without compromising their bioactivity, while maintaining adequate mechanical properties. In this work, we report the fabrication and characterization of cellulose and collagen based micro-nano structured scaffolds using human osteoblasts (HOB) for BTE applications. These porous micro-nano structured scaffolds (average pore diameter 190 +/- 10 microm) exhibited mechanical properties in the mid range of human trabecular bone (compressive modulus 266.75 +/- 33.22 MPa and strength 12.15 3 +/- 2.23 MPa). These scaffolds supported the greater adhesion and phenotype maintenance of cultured HOB as reflected by higher levels of osteogenic enzyme alkaline phosphatase and mineral deposition compared to control polyester micro-nano structured scaffolds of identical pore properties. These natural polymer based micro-nano structured scaffolds may serve as alternatives to polyester based scaffolds for BTE applications.
[Show abstract][Hide abstract] ABSTRACT: Tissue engineering aims to repair, restore, and regenerate lost or damaged tissues by using biomaterials, cells, mechanical forces and factors (chemical and biological) alone or in combination. Growth factors are routinely used in the tissue engineering approach to expedite the process of regeneration. The growth factor approach has been hampered by several complications including high dose requirements, lower half-life, protein instability, higher costs and undesired side effects. Recently a variety of alternative small molecules of both natural and synthetic origin have been explored as alternatives to growth factors for tissue regeneration applications. Small molecules are simple biochemical components that elicit certain cellular responses through signaling cascades. Small molecules present a viable alternative to biological factors. Small molecule strategies can reduce various side effects, maintain bioactivity in a biological environment and minimize cost issues associated with complex biological growth factors. This manuscript focuses on three-osteoinductive small molecules, namely melatonin, resveratrol (from natural sources) and purmorphamine (synthetically designed) as inducers of bone formation and osteogenic differentiation of stem cells. Efforts have been made to summarize possible biological pathways involved in the action of each of these drugs. Melatonin is known to affect Mitogen Activated Protein (MAP) kinase, Bone morphogenic protein (BMP) and canonical wnt signaling. Resveratrol is known to activate cascades involving Int mammalian homologue of drosophila wingless protein (Wnt) and NAD-dependent deacetylase sirtuin-1 (Sirt1). Purmorphamine is a Hedgehog (Hh) pathway agonist as it acts on Smoothened (Smo) receptors. These mechanisms and the way they are affected by the respective small molecules will also be discussed in the manuscript.
No preview · Article · Feb 2013 · Current pharmaceutical design
[Show abstract][Hide abstract] ABSTRACT: Treatment of large bone defects poses a real challenge to the orthopaedic surgeon. The surgeon often times calls on creativity in the form of bone graft substitutes to help mend large bone defects. The bone graft substitutes used today include inorganic compounds such as calcium phosphate, osteoconductive composites which act as a scaffold to allow for new bone growth, and some may include osteoinductive proteins which provide signals to the microenvironment promoting osteogenesis. Autologous bone grafts are still the gold standard and this creates a risk of harvest site morbidity and the defect may be too large for autologous bone alone. Injuries requiring tendon or ligament reconstruction rely upon the use of bone blocks in the form of bone-tendon-bone grafts, which can also create a hurdle for the orthopaedist. We have reviewed the current literature and recent patents available on bone graft substitutes and bone blocks for bonetendon- bone grafts and have described new biomaterials and therapeutics available to the orthopaedic surgeon.
No preview · Article · Jul 2012 · Recent Patents on Biomedical Engineering