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1.  On the Biomimetic Design of Agile-Robot Legs 
Sensors (Basel, Switzerland)  2011;11(12):11305-11334.
The development of functional legged robots has encountered its limits in human-made actuation technology. This paper describes research on the biomimetic design of legs for agile quadrupeds. A biomimetic leg concept that extracts key principles from horse legs which are responsible for the agile and powerful locomotion of these animals is presented. The proposed biomimetic leg model defines the effective leg length, leg kinematics, limb mass distribution, actuator power, and elastic energy recovery as determinants of agile locomotion, and values for these five key elements are given. The transfer of the extracted principles to technological instantiations is analyzed in detail, considering the availability of current materials, structures and actuators. A real leg prototype has been developed following the biomimetic leg concept proposed. The actuation system is based on the hybrid use of series elasticity and magneto-rheological dampers which provides variable compliance for natural motion. From the experimental evaluation of this prototype, conclusions on the current technological barriers to achieve real functional legged robots to walk dynamically in agile locomotion are presented.
PMCID: PMC3251984  PMID: 22247667
legged robots; agile quadrupeds; biomimetic design; new actuators for robots
2.  Evolving application of biomimetic nanostructured hydroxyapatite 
By mimicking Nature, we can design and synthesize inorganic smart materials that are reactive to biological tissues. These smart materials can be utilized to design innovative third-generation biomaterials, which are able to not only optimize their interaction with biological tissues and environment, but also mimic biogenic materials in their functionalities. The biomedical applications involve increasing the biomimetic levels from chemical composition, structural organization, morphology, mechanical behavior, nanostructure, and bulk and surface chemical–physical properties until the surface becomes bioreactive and stimulates cellular materials. The chemical–physical characteristics of biogenic hydroxyapatites from bone and tooth have been described, in order to point out the elective sides, which are important to reproduce the design of a new biomimetic synthetic hydroxyapatite. This review outlines the evolving applications of biomimetic synthetic calcium phosphates, details the main characteristics of bone and tooth, where the calcium phosphates are present, and discusses the chemical–physical characteristics of biomimetic calcium phosphates, methods of synthesizing them, and some of their biomedical applications.
PMCID: PMC3781698  PMID: 24198477
hydroxyapatite; nanocrystals; biomimetism; biomaterials; drug delivery; remineralization
3.  Biomimetic Magnetite Formation: From Biocombinatorial Approaches to Mineralization Effects 
Langmuir  2014;30(8):2129-2136.
Biological materials typically display complex morphologies and hierarchical architectures, properties that are hardly matched by synthetic materials. Understanding the biological control of mineral properties will enable the development of new synthetic approaches toward biomimetic functional materials. Here, we combine biocombinatorial approaches with a proteome homology search and in vitro mineralization assays to assess the role of biological determinants in biomimetic magnetite mineralization. Our results suggest that the identified proteins and biomimetic polypeptides influence nucleation in vitro. Even though the in vivo role cannot be directly determined from our experiments, we can rationalize the following design principles: proteins, larger complexes, or membrane components that promote nucleation in vivo are likely to expose positively charged residues to a negatively charged crystal surface. In turn, components with acidic (negatively charged) functionality are nucleation inhibitors, which stabilize an amorphous structure through the coordination of iron.
PMCID: PMC3958130  PMID: 24499323
4.  Biomimetic coatings for bone tissue engineering of critical-sized defects 
Journal of the Royal Society Interface  2010;7(Suppl 5):S631-S647.
The repair of critical-sized bone defects is still challenging in the fields of implantology, maxillofacial surgery and orthopaedics. Current therapies such as autografts and allografts are associated with various limitations. Cytokine-based bone tissue engineering has been attracting increasing attention. Bone-inducing agents have been locally injected to stimulate the native bone-formation activity, but without much success. The reason is that these drugs must be delivered slowly and at a low concentration to be effective. This then mimics the natural method of cytokine release. For this purpose, a suitable vehicle was developed, the so-called biomimetic coating, which can be deposited on metal implants as well as on biomaterials. Materials that are currently used to fill bony defects cannot by themselves trigger bone formation. Therefore, biological functionalization of such materials by the biomimetic method resulted in a novel biomimetic coating onto different biomaterials. Bone morphogenetic protein 2 (BMP-2)-incorporated biomimetic coating can be a solution for a large bone defect repair in the fields of dental implantology, maxillofacial surgery and orthopaedics. Here, we review the performance of the biomimetic coating both in vitro and in vivo.
PMCID: PMC2952178  PMID: 20484228
biomimetic; biphasic calcium phosphate coating; bone morphogenetic protein-2; bone tissue engineering
5.  Convection driven generation of long-range material gradients 
Biomaterials  2009;31(9):2686.
Natural materials exhibit anisotropy with variations in soluble factors, cell distribution, and matrix properties. The ability to recreate the heterogeneity of the natural materials is a major challenge for investigating cell-material interactions and for developing biomimetic materials. Here we present a generic fluidic approach using convection and alternating flow to rapidly generate multi-centimeter gradients of biomolecules, polymers, beads and cells and cross-gradients of two species in a microchannel. Accompanying theoretical estimates and simulations of gradient growth provide design criteria over a range of material properties. A poly(ethyleneglycol) hydrogel gradient, a porous collagen gradient and a composite material with a hyaluronic acid/gelatin cross-gradient were generated with continuous variations in material properties and in their ability to regulate cellular response. This simple yet generic fluidic platform should prove useful for creating anisotropic biomimetic materials and high-throughput platforms for investigating cell-microenvironment interaction.
PMCID: PMC2813888  PMID: 20035990
anisotropic materials; composite materials; microfluidics; gradients
6.  A simplified genetic design for mammalian enamel 
Biomaterials  2011;32(12):3151-3157.
A biomimetic replacement for tooth enamel is urgently needed because dental caries is the most prevalent infectious disease to affect man. Here, design specifications for an enamel replacement material inspired by Nature are deployed for testing in an animal model. Using genetic engineering we created a simplified enamel protein matrix precursor where only one, rather than dozens of amelogenin isoforms, contributed to enamel formation. Enamel function and architecture were unaltered, but the balance between the competing materials properties of hardness and toughness was modulated. While the other amelogenin isoforms make a modest contribution to optimal biomechanical design, the enamel made with only one amelogenin isoform served as a functional substitute. Where enamel has been lost to caries or trauma a suitable biomimetic replacement material could be fabricated using only one amelogenin isoform, thereby simplifying the protein matrix parameters by one order of magnitude.
PMCID: PMC3045652  PMID: 21295848
Biomimetic material; Biomineralization; ECM (extracellular matrix); Fracture toughness: Genetic engineering; Mechanical properties; Molecular biology
7.  Laparoscopic Repair of Inguinal Hernia with Biomimetic Matrix 
Biomimetic matrix material may be suitable for the long-term repair of inguinal hernia.
Background and Objectives:
Materials utilized for the repair of hernias fall into 2 broad categories, synthetics and biologics. Each has its merits and drawbacks. The synthetics have a permanent, inherent strength but are associated with some incidence of chronic pain. The biologics rely on variable tissue regeneration to give strength to the repair, limiting their use to specific situations. However, thanks to their transient presence and tissue ingrowth, the biologics do not result in a significant incidence of chronic pain. We studied the use of a biomimetic (REVIVE, Biomerix Corporation, Fremont, CA) in this setting in an attempt to obviate the disadvantages of each material.
Fourteen patients underwent laparoscopic repair by totally extraperitoneal and transabdominal preperitoneal techniques of 16 inguinal hernias. Follow-up was as long as 19 mo, and 8 patients were followed for > 12 mo. There were no recurrences and a 5% incidence of functionally insignificant discomfort.
REVIVE is shown in histology and in vivo to demonstrate regeneration and tissue ingrowth into the polycarbonate/polyuria matrix similar to that in the biologics rather than scarring or encapsulation. There were no recurrences, indicating its strength and resilience as a permanent repair similar to that in the synthetics.
This is proof of the concept that a biomimetic may bridge the gap between the biologics and synthetics and may be able to be utilized on a regular basis with the benefits of both materials and without their drawbacks.
PMCID: PMC3558893  PMID: 23484565
Revive; biomimetic; synthetics; biologics; hernia
8.  Rapid Fabrication of Living Tissue Models by Collagen Plastic Compression: Understanding Three-Dimensional Cell Matrix Repair In Vitro 
Advances in Wound Care  2013;2(4):176-184.
To produce biomimetic collagen scaffolds for tissue modeling and as tissue-engineered implants.
Control of collagen fibril material parameters in collagen hydrogel scaffolds by using plastic compression (PC), resulting in direct control of cell proliferation, cell migration, and cell–cell interaction.
We were able to control the density of collagen in such scaffolds from between 0.2% and 30%, and controllably layer the fibrils in the Z-plane. Cell migration was observed in gels where a gradient of collagen density was present. In these gels, cells preferentially migrated toward the collagen-dense areas. Cell proliferation rates were measurably higher in dense collagen gels.
The use of PC to control material properties of collagen hydrogels results in collagen scaffolds that are biomimetic. These collagen gels reproduce the relevant matrix-mechanical environment in which behavior is more representative of that found in vivo.
The material properties of native collagen type I gels can be engineered to match those found in tissues in vivo to elicit more biomimetic cell behavior.
PMCID: PMC3840553  PMID: 24527341
9.  Bone Regeneration of Rat Tibial Defect by Zinc-Tricalcium Phosphate (Zn-TCP) Synthesized from Porous Foraminifera Carbonate Macrospheres 
Marine Drugs  2013;11(12):5148-5158.
Foraminifera carbonate exoskeleton was hydrothermally converted to biocompatible and biodegradable zinc-tricalcium phosphate (Zn-TCP) as an alternative biomimetic material for bone fracture repair. Zn-TCP samples implanted in a rat tibial defect model for eight weeks were compared with unfilled defect and beta-tricalcium phosphate showing accelerated bone regeneration compared with the control groups, with statistically significant bone mineral density and bone mineral content growth. CT images of the defect showed restoration of cancellous bone in Zn-TCP and only minimal growth in control group. Histological slices reveal bone in-growth within the pores and porous chamber of the material detailing good bone-material integration with the presence of blood vessels. These results exhibit the future potential of biomimetic Zn-TCP as bone grafts for bone fracture repair.
PMCID: PMC3877909  PMID: 24351911
biomimetic; zinc-tricalcium phosphate; foraminifera; bone defect; bone regeneration
10.  Synthesis and Characterization of Hybrid Hyaluronic Acid-Gelatin Hydrogels 
Biomacromolecules  2013;14(4):1085-1092.
Biomimetic hybrid hydrogels have generated broad interest in tissue engineering and regenerative medicine. Hyaluronic acid (HA) and gelatin (hydrolyzed collagen) are naturally derived polymers and biodegradable under physiological conditions. Moreover, collagen and HA are major components of the extracellular matrix (ECM) in most of the tissues (e.g. cardiovascular, cartilage, neural). When used as a hybrid material, HA-gelatin hydrogels may enable mimicking the ECM of native tissues. Although HA-gelatin hybrid hydrogels are promising biomimetic substrates, their material properties have not been thoroughly characterized in the literature. Herein, we generated hybrid hydrogels with tunable physical and biological properties by using different concentrations of HA and gelatin. The physical properties of the fabricated hydrogels including swelling ratio, degradation, and mechanical properties were investigated. In addition, in vitro cellular responses in both two and three dimensional (2D and 3D) culture conditions were assessed. It was found that the addition of gelatin methacrylate (GelMA) into HA methacrylate (HAMA) promoted cell spreading in the hybrid hydogels. Moreover, the hybrid hydrogels showed significantly improved mechanical properties compared to their single component analogs. The HAMA-GelMA hydrogels exhibited remarkable tunability behavior and may be useful for cardiovascular tissue engineering applications.
PMCID: PMC3643200  PMID: 23419055
hyaluronic acid; gelatin; hydrogel; extracellular matrix; tissue engineering
11.  Enhanced endothelial cell functions on rosette nanotube-coated titanium vascular stents 
One of the main problems with current vascular stents is a lack of endothelial cell interactions, which if sufficient, would create a uniform healthy endothelium masking the underlying foreign metal from inflammatory cell interference. Moreover, if endothelial cells from the arterial wall do not adhere to the stent, the stent can become loose and dislodge. Therefore, the objective of this in vitro study was to design a novel biomimetic nanostructured coating (that does not contain drugs) on conventional vascular stent materials (specifically, titanium) for improving vascular stent applications. Rosette nanotubes (RNTs) are a new class of biomimetic nanotubes that self-assemble from DNA base analogs and have been shown in previous studies to sufficiently coat titanium and enhance osteoblast cell functions. RNTs have many desirable properties for use as vascular stent coatings including spontaneous self-assembly in body fluids, tailorable surface chemistry for specific implant applications, and nanoscale dimensions similar to those of the natural vascular extracellular matrix. Importantly, the results of this study provided the first evidence that RNTs functionalized with lysine (RNT–K), even at low concentrations, significantly increase endothelial cell density over uncoated titanium. Specifically, 0.01 mg/mL RNT–K coated titanium increased endothelial cell density by 37% and 52% compared to uncoated titanium after 4 h and three days, respectively. The excellent cytocompatibility properties of RNTs (as demonstrated here for the first time for endothelial cells) suggest the need for the further exploration of these novel nanostructured materials for vascular stent applications.
PMCID: PMC2720744  PMID: 19516887
stents; nanotechnology; self-assembly; rosette nanotubes; endothelial cells; titanium
12.  Human Endothelial Cell Interaction with Biomimetic Surfactant Polymers Containing Peptide Ligands from the Heparin Binding Domain of Fibronectin 
Tissue engineering  2005;11(1-2):226-236.
Biomimetic materials that mimic the extracellular matrix (ECM) provide a means to control cellular functions such as adhesion and growth, which are vital to successful engineering of tissue-incorporated biomaterials. Novel “ECM-like” biomimetic surfactant polymers consisting of a poly(vinyl amine) backbone with pendant cell-adhesive peptides derived from one of the heparin-binding domains of fibronectin were developed to improve endothelial cell adhesion and growth on vascular biomaterials. Heparin-binding peptide (HBP) sequences, alone and in combination with RGD peptides, were examined for their ability to promote human pulmonary artery endothelial cell (HPAEC) adhesion and growth (HBP1, WQPPRARI; HBP2, SPPRRARVT; HBP1:RGD; and HBP2:RGD) and compared with cell adhesion and growth on fibronectin and on negative control polymer surfaces in which alanines were substituted for the positively charged arginine residues in the two peptides. The results showed that HPAECs adhered and spread equally well on all HBP-containing polymers and the positive fibronectin control, showing similar stress fiber and focal adhesion formation. However, the HBP alone was unable to support long-term HPAEC growth and survival, showing a loss of focal adhesions and cytoskeletal disorganization by 24 h after seeding. With the addition of RGD, the surfaces behaved similarly or better than fibronectin. The negative control polymers showed little to no initial cell attachment, and the addition of soluble heparin to the medium reduced initial cell adhesion on both the HBP2 and HBP2:RGD surfaces. These results indicate that the HBP surfaces promote initial HPAEC adhesion and spreading, but not long-term survival.
PMCID: PMC1236992  PMID: 15738677
13.  Mechanical characterization of biomimetic membranes by micro-shaft poking 
The popularity of biomimetic membranes has recently increased due to their biomedical applications such as tissue engineering/regenerative medicine and biosensors. Characterization of the viscoelastic properties of these membranes is important in developing functional membranes. A new micro-shaft poking technique has been developed, which is free from the complication of substrate backing, and which is normally an intractable problem in conventional indentation testing of membrane materials. A tailored indentation apparatus with a spherical indenter and a force resolution and displacement of 1 μN and 1 μm was constructed. Alginate and agarose were used to fabricate biomimetic membranes. Chicken epidermis was examined to represent a real biological tissue. The results show that the elastic modulus increased with concentration in hydrogels. Epidermis moduli appeared to increase with increased strain. Stress relaxation tests have also been conducted to examine the time-dependent behaviours of various hydrogels and a viscoelastic model has been correspondingly developed and applied to describe the experimental results. Potential applications of this new instrument to other membranes, both artificial and biological, have also been addressed.
PMCID: PMC2659696  PMID: 18753124
instrumentation; hydrogel; mechanical characterization; microengineering; biological tissue
14.  Aloe vera Induced Biomimetic Assemblage of Nucleobase into Nanosized Particles 
PLoS ONE  2012;7(3):e32049.
Biomimetic nano-assembly formation offers a convenient and bio friendly approach to fabricate complex structures from simple components with sub-nanometer precision. Recently, biomimetic (employing microorganism/plants) synthesis of metal and inorganic materials nano-particles has emerged as a simple and viable strategy. In the present study, we have extended biological synthesis of nano-particles to organic molecules, namely the anticancer agent 5-fluorouracil (5-FU), using Aloe vera leaf extract.
The 5-FU nano- particles synthesized by using Aloe vera leaf extract were characterized by UV, FT-IR and fluorescence spectroscopic techniques. The size and shape of the synthesized nanoparticles were determined by TEM, while crystalline nature of 5-FU particles was established by X-ray diffraction study. The cytotoxic effects of 5-FU nanoparticles were assessed against HT-29 and Caco-2 (human adenocarcinoma colorectal) cell lines.
Transmission electron microscopy and atomic force microscopic techniques confirmed nano-size of the synthesized particles. Importantly, the nano-assembled 5-FU retained its anticancer action against various cancerous cell lines.
In the present study, we have explored the potential of biomimetic synthesis of nanoparticles employing organic molecules with the hope that such developments will be helpful to introduce novel nano-particle formulations that will not only be more effective but would also be devoid of nano-particle associated putative toxicity constraints.
PMCID: PMC3293877  PMID: 22403622
15.  Subtleties of biomineralisation revealed by manipulation of the eggshell membrane 
Biomaterials  2011;32(34):8743-8752.
Biocalcification of collagen matrices with calcium phosphate and biosilicification of diatom frustules with amorphous silica are two discrete processes that have intrigued biologists and materials scientists for decades. Recent advancements in the understanding of the mechanisms involved in these two biomineralisation processes have resulted in the use of biomimetic strategies to replicate these processes separately using polyanionic, polycationic or zwitterionic analogues of extracellular matrix proteins to stabilise amorphous mineral precursor phases. To date, there is a lack of a universal model that enables the subtleties of these two apparently dissimilar biomineralisation processes to be studied together. Here, we utilise the eggshell membrane as a universal model for differential biomimetic calcification and silicification. By manipulating the eggshell membrane to render it permeable to stabilised mineral precursors, it is possible to introduce nanostructured calcium phosphate or silica into eggshell membrane fibre cores or mantles. We provide a model for infiltrating the two compartmental niches of a biopolymer membrane with different intrafibre minerals to obtain materials with potentially improved structure-property relationships.
PMCID: PMC3183170  PMID: 21864897
apatite; biomineralisation; silica; membrane
16.  Remineralization of artificial dentinal caries lesions by biomimetically modified Mineral Trioxide Aggregate 
Acta Biomaterialia  2011;8(2):836-842.
Fluoride-releasing restorative materials are available for remineralization of enamel and root caries. However, dentin remineralization is more difficult than enamel remineralization due to the paucity of apatite seed crystallites along the lesion surface for heterogeneous crystal growth. Extracellular matrix proteins play critical roles in controlling apatite nucleation/growth in collagenous tissues. This study examined the remineralization efficacy of mineral trioxide aggregate (MTA) in phosphate-containing simulated body fluid (SBF) by incorporating polyacrylic acid and sodium tripolyphosphate as biomimetic analogs of matrix proteins for remineralizing caries-like dentin. Artificial caries-like dentin lesions incubated in SBF were remineralized over a 6-week period using MTA or MTA containing biomimetic analogs in the absence or presence of dentin adhesive application. Lesion depths and integrated mineral loss were monitored with micro-computed tomography. Ultrastructure of baseline and remineralized lesions were examined by transmission electron microscopy. Dentin remineralization was best achieved using MTA containing biomimetic analogs regardless of whether an adhesive was applied; dentinal tubules within the remineralized dentin were occluded by apatite. It is concluded that the MTA version employed in the study may be doped with biomimetic analogs for remineralization of unbonded and bonded artificial caries-like lesions in the presence of SBF.
PMCID: PMC3253923  PMID: 22085925
biomimetics; caries; micro-computed tomography; mineral trioxide aggregate; tubular occlusion
17.  Clues for biomimetics from natural composite materials 
Nanomedicine (London, England)  2012;7(9):1409-1423.
Bio-inspired material systems are derived from different living organisms such as plants, arthropods, mammals and marine organisms. These biomaterial systems from nature are always present in the form of composites, with molecular-scale interactions optimized to direct functional features. With interest in replacing synthetic materials with natural materials due to biocompatibility, sustainability and green chemistry issues, it is important to understand the molecular structure and chemistry of the raw component materials to also learn from their natural engineering, interfaces and interactions leading to durable and highly functional material architectures. This review will focus on applications of biomaterials in single material forms, as well as biomimetic composites inspired by natural organizational features. Examples of different natural composite systems will be described, followed by implementation of the principles underlying their composite organization into artificial bio-inspired systems for materials with new functional features for future medicine.
PMCID: PMC3567446  PMID: 22994958
bio-inspired; cellulose; collagen; resilin; silk; SP1
18.  Clinical Performance of a New Biomimetic Double Network Material 
The Open Dentistry Journal  2013;7:118-122.
The development of ceramics during the last years was overwhelming. However, the focus was laid on the hardness and the strength of the restorative materials, resulting in high antagonistic tooth wear. This is critical for patients with bruxism.
The purpose of this study was to evaluate the clinical performance of the new double hybrid material for non-invasive treatment approaches.
Material and Methods:
The new approach of the material tested, was to modify ceramics to create a biomimetic material that has similar physical properties like dentin and enamel and is still as strong as conventional ceramics.
The produced crowns had a thickness ranging from 0.5 to 1.5 mm. To evaluate the clinical performance and durability of the crowns, the patient was examined half a year later. The crowns were still intact and soft tissues appeared healthy and this was achieved without any loss of tooth structure.
The material can be milled to thin layers, but is still strong enough to prevent cracks which are stopped by the interpenetrating polymer within the network. Depending on the clinical situation, minimally- up to non-invasive restorations can be milled.
Clinical Relevance:
Dentistry aims in preservation of tooth structure. Patients suffering from loss of tooth structure (dental erosion, Amelogenesis imperfecta) or even young patients could benefit from minimally-invasive crowns. Due to a Vickers hardness between dentin and enamel, antagonistic tooth wear is very low. This might be interesting for treating patients with bruxism.
PMCID: PMC3807582  PMID: 24167534
CAD/CAM; Enamic; double network hybrid material; non-invasive treatment; dental erosion; bruxism.
19.  Biomimetic materials research: what can we really learn from nature's structural materials? 
Nature provides a wide range of materials with different functions and which may serve as a source of bio-inspiration for the materials scientist. The article takes the point of view that a successful translation of these ideas into the technical world requires more than the observation of nature. A thorough analysis of structure-function relations in natural tissues must precede the engineering of new bio-inspired materials. There are, indeed, many opportunities for lessons from the biological world: on growth and functional adaptation, about hierarchical structuring, on damage repair and self-healing. Biomimetic materials research is becoming a rapidly growing and enormously promising field. Serendipitous discovery from the observation of nature will be gradually replaced by a systematic approach involving the study of natural tissues in materials laboratories, the application of engineering principles to the further development of bio-inspired ideas and the generation of specific databases.
PMCID: PMC2373394  PMID: 17341452
bionic; bio-inspired; adaptive; self-healing; hierarchical materials
20.  Application of Calcium Phosphate Materials in Dentistry 
Calcium phosphate materials are similar to bone in composition and in having bioactive and osteoconductive properties. Calcium phosphate materials in different forms, as cements, composites, and coatings, are used in many medical and dental applications. This paper reviews the applications of these materials in dentistry. It presents a brief history, dental applications, and methods for improving their mechanical properties. Notable research is highlighted regarding (1) application of calcium phosphate into various fields in dentistry; (2) improving mechanical properties of calcium phosphate; (3) biomimetic process and functionally graded materials. This paper deals with most common types of the calcium phosphate materials such as hydroxyapatite and tricalcium phosphate which are currently used in dental and medical fields.
PMCID: PMC3710628  PMID: 23878541
21.  Neurite Outgrowth at the Biomimetic Interface 
Annals of biomedical engineering  2010;38(6):2210-2225.
Understanding the cues that guide axons and how we can optimize these cues to achieve directed neuronal growth is imperative for neural tissue engineering. Cells in the local environment influence neurons with a rich combination of cues. This study deconstructs the complex mixture of guidance cues by working at the biomimetic interface - isolating the topographical information presented by cells and determining its capacity to guide neurons. We generated replica materials presenting topographies of oriented astrocytes (ACs), endothelial cells (ECs), and Schwann cells (SCs) as well as computer-aided design materials inspired by the contours of these cells (bioinspired-CAD). These materials presented distinct topographies and anisotropies and in all cases were sufficient to guide neurons. Dorsal root ganglia (DRG) cells and neurites demonstrated the most directed response on bioinspired-CAD materials which presented anisotropic features with 90° edges. DRG alignment was strongest on SC bioinspired-CAD materials followed by AC bioinspired-CAD materials, with more uniform orientation to EC bioinspired-CAD materials. Alignment was strongest on SC replica materials followed by AC and EC replicas. These results suggest that the topographies of anisotropic tissue structures are sufficient for neuronal guidance. This work is discussed in the context of feature dimensions, morphology, and guidepost hypotheses.
PMCID: PMC3016852  PMID: 20440561
astrocyte; Schwann cell; endothelial cell; dorsal root ganglia; biomaterial; replica; topography; axon guidance; contact guidance
22.  Live Diatom Silica Immobilization of Multimeric and Redox-Active Enzymes 
Living organisms are adept in forming inorganic materials (biominerals) with unique structures and properties that exceed the capabilities of engineered materials. Biomimetic materials syntheses are being developed that aim at replicating the advantageous properties of biominerals in vitro and endow them with additional functionalities. Recently, proof-of-concept was provided for an alternative approach that allows for the production of biomineral-based functional materials in vivo. In this approach, the cellular machinery for the biosynthesis of nano-/micropatterned SiO2 (silica) structures in diatoms was genetically engineered to incorporate a monomeric, cofactor-independent (“simple”) enzyme, HabB, into diatom silica. In the present work, it is demonstrated that this approach is also applicable for enzymes with “complex” activity requirements, including oligomerization, metal ions, organic redox cofactors, and posttranslational modifications. Functional expression of the enzymes β-glucuronidase, glucose oxidase, galactose oxidase, and horseradish peroxidase in the diatom Thalassiosira pseudonana was accomplished, and 66 to 78% of the expressed enzymes were stably incorporated into the biosilica. The in vivo incorporated enzymes represent approximately 0.1% (wt/wt) of the diatom biosilica and are stabilized against denaturation and proteolytic degradation. Furthermore, it is demonstrated that the gene construct for in vivo immobilization of glucose oxidase can be utilized as the first negative selection marker for diatom genetic engineering.
PMCID: PMC3255611  PMID: 22057862
23.  Elucidating Multiscale Periosteal Mechanobiology: A Key to Unlocking the Smart Properties and Regenerative Capacity of the Periosteum? 
The periosteum, a thin, fibrous tissue layer covering most bones, resides in a dynamic, mechanically loaded environment. The periosteum also provides a niche for mesenchymal stem cells. The mechanics of periosteum vary greatly between species and anatomical locations, indicating the specialized role of periosteum as bone's bounding membrane. Furthermore, periosteum exhibits stress-state-dependent mechanical and material properties, hallmarks of a smart material. This review discusses what is known about the multiscale mechanical and material properties of the periosteum as well as their potential effect on the mechanosensitive progenitor cells within the tissue. Furthermore, this review addresses open questions and barriers to understanding periosteum's multiscale structure–function relationships. Knowledge of the smart material properties of the periosteum will maximize the translation of periosteum and substitute periosteum to regenerative medicine, facilitate the development of biomimetic tissue-engineered periosteum for use in instances where the native periosteum is lacking or damaged, and provide inspiration for a new class of smart, advanced materials.
PMCID: PMC3589889  PMID: 23189933
24.  An Overview of Poly(lactic-co-glycolic) Acid (PLGA)-Based Biomaterials for Bone Tissue Engineering 
Poly(lactic-co-glycolic) acid (PLGA) has attracted considerable interest as a base material for biomedical applications due to its: (i) biocompatibility; (ii) tailored biodegradation rate (depending on the molecular weight and copolymer ratio); (iii) approval for clinical use in humans by the U.S. Food and Drug Administration (FDA); (iv) potential to modify surface properties to provide better interaction with biological materials; and (v) suitability for export to countries and cultures where implantation of animal-derived products is unpopular. This paper critically reviews the scientific challenge of manufacturing PLGA-based materials with suitable properties and shapes for specific biomedical applications, with special emphasis on bone tissue engineering. The analysis of the state of the art in the field reveals the presence of current innovative techniques for scaffolds and material manufacturing that are currently opening the way to prepare biomimetic PLGA substrates able to modulate cell interaction for improved substitution, restoration, or enhancement of bone tissue function.
PMCID: PMC3975359  PMID: 24590126
bone; composite; PLGA; scaffolds; tissue engineering
25.  Electrospun Nanostructured Fibers of Collagen-Biomimetic Apatite on Titanium Alloy 
Titanium and its alloys are currently the mainly used materials to manufacture orthopaedic implants due to their excellent mechanical properties and corrosion resistance. Although these materials are bioinert, the improvement of biological properties (e.g., bone implant contact) can be obtained by the application of a material that mimics the bone extracellular matrix. To this aim, this work describes a new method to produce nanostructured collagen-apatite composites on titanium alloy substrate, by combining electrospinning and biomimetic mineralization. The characterization results showed that the obtained mineralized scaffolds have morphological, structural, and chemical compositional features similar to natural bone extracellular matrix. Finally, the topographic distribution of the chemical composition in the mineralized matrix evaluated by Fourier Transform Infrared microspectroscopy demonstrated that the apatite nanocrystals cover the collagen fibers assembled by the electrospinning.
PMCID: PMC3287036  PMID: 22400013

Results 1-25 (52387)