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1.  Calcifying tissue regeneration via biomimetic materials chemistry 
Journal of the Royal Society Interface  2014;11(101):20140537.
Materials chemistry is making a fundamental impact in regenerative sciences providing many platforms for tissue development. However, there is a surprising paucity of replacements that accurately mimic the structure and function of the structural fabric of tissues or promote faithful tissue reconstruction. Methodologies in biomimetic materials chemistry have shown promise in replicating morphologies, architectures and functional building blocks of acellular mineralized tissues dentine, enamel and bone or that can be used to fully regenerate them with integrated cell populations. Biomimetic materials chemistry encompasses the two processes of crystal formation and mineralization of crystals into inorganic formations on organic templates. This review will revisit the successes of biomimetics materials chemistry in regenerative medicine, including coccolithophore simulants able to promote in vivo bone formation. In-depth knowledge of biomineralization throughout evolution informs the biomimetic materials chemist of the most effective techniques for regenerative framework construction exemplified via exploitation of liquid crystals (LCs) and complex self-organizing media. Therefore, a new innovative direction would be to create chemical environments that perform reaction–diffusion exchanges as the basis for building complex biomimetic inorganic structures. This has evolved widely in biology, as have LCs, serving as self-organizing templates in pattern formation of structural biomaterials. For instance, a study is highlighted in which artificially fabricated chiral LCs, made from bacteriophages are transformed into a faithful copy of enamel. While chemical-based strategies are highly promising at creating new biomimetic structures there are limits to the degree of complexity that can be generated. Thus, there may be good reason to implement living or artificial cells in ‘morphosynthesis’ of complex inorganic constructs. In the future, cellular construction is probably key to instruct building of ultimate biomimetic hierarchies with a totality of functions.
PMCID: PMC4223895  PMID: 25320063
biomineralization; regenerative medicine; bioinorganic materials chemistry
2.  Biomimetic ceramics for periodontal regeneration in infrabony defects: A systematic review 
Biomimetic materials are widely used in the treatment of osseous defects as an alternative to autogenous bone graft. The aim of this article was to review the literature and compare the quality of published articles on biomimetic ceramic material used for periodontal regeneration in the treatment of infrabony defects and to discuss the future direction of research. The bibliographic databases PubMed, Ebsco, and Google Scholar were searched from January 2000 to March 2014 for randomized control trials in which biomimetic ceramic graft material was compared with open flap debridement or in combination with any other regenerative material. To avoid the variability of the search terms, the thesaurus Mesh was used. The primary outcome variable assessed was clinical attachment level (CAL). The screening of eligible studies, assessment of the methodological quality of the trials, and data extraction were performed by two observers independently. Twenty-six articles were identified and included in this systematic review. The primary outcome was CAL. Out of the 26 studies, 24 showed more than 2 mm of CAL gain. The difference in CAL change between test and control groups varied from 1.2 mm to 5.88 mm with respect to different biomaterials/biomimetic materials, which was clinically and statistically significant. Meta-analysis was not done due to heterogeneity in results between studies. Overall, biomaterials were found to be more effective than open flap debridement in improving the attachment levels in intraosseous defects. Future research should aim at increasing the osteoinductive capacity of these biomimetic graft materials.
PMCID: PMC4278107  PMID: 25558455
Biomaterials; biomimetic materials; bone grafts; infrabony defects; systematic review
3.  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
4.  Changes in Stiffness of Resin-infiltrated Demineralized Dentin after Remineralization with a Bottom-up Biomimetic Approach 
Acta biomaterialia  2009;6(4):1453-1461.
This study examined changes in elastic modulus, mineral density and ultrastructure of resin-infiltrated dentin after biomimetic remineralization. Sixty demineralized dentin beams were infiltrated with Clearfil Tri-S Bond, One-Step or Prime&Bond NT. They were immersed in simulated body fluid (SBF) for one week to maximize water sorption before determining the baseline elastic moduli. For each adhesive (N=20), half of the beams remained immersed in SBF (control). The rest were immersed in a biomimetic remineralization medium. The elastic moduli were measured weekly for 15 additional weeks. Representative remineralized specimens were evaluated with X-ray microtomography and transmission electron microscopy (TEM). The elastic moduli of control resin-infiltrated dentin remained consistently low, while those immersed in the biomimetic remineralization medium increased by 55–118% after 4-months. X-ray microtomography of the remineralized specimens revealed decreases in mineral density from the beam surface to the beam core that was indicative of external mineral aggregation and internal mineral deposition. Interfibrillar and intrafibrillar remineralization of resin-sparse intertubular dentin were seen under TEM together with remineralized peritubular dentin. Biomimetic remineralization occurs by diffusion of nanoprecursors and biomimetic analogs in completely demineralized resin-infiltrated dentin and proceeds without the contribution of materials released from a mineralized dentin base.
PMCID: PMC2830350  PMID: 19887126
Bio-remineralization; Macro-hybrid layer; Intrafibrillar remineralization; Elastic modulus; Peritubular dentin
5.  Soluble and insoluble signals sculpt osteogenesis in angiogenesis 
The basic tissue engineering paradigm is tissue induction and morphogenesis by combinatorial molecular protocols whereby soluble molecular signals are combined with insoluble signals or substrata. The insoluble signal acts as a three-dimensional scaffold for the initiation of de novo tissue induction and morphogenesis. The osteogenic soluble molecular signals of the transforming growth factor-β (TGF-β) supergene family, the bone morphogenetic/osteogenic proteins (BMPs/OPs) and, uniquely in the non-human primate Papio ursinus (P. ursinus), the three mammalian TGF-β isoforms induce bone formation as a recapitulation of embryonic development. In this paper, I discuss the pleiotropic activity of the BMPs/OPs in the non-human primate P. ursinus, the induction of bone by transitional uroepithelium, and the apparent redundancy of molecular signals initiating bone formation by induction including the three mammalian TGF-β isoforms. Amongst all mammals tested so far, the three mammalian TGF-β isoforms induce endochondral bone formation in the non-human primate P. ursinus only. Bone tissue engineering starts by erecting scaffolds of biomimetic biomaterial matrices that mimic the supramolecular assembly of the extracellular matrix of bone. The molecular scaffolding lies at the hearth of all tissue engineering strategies including the induction of bone formation. The novel concept of tissue engineering is the generation of newly formed bone by the implantation of “smart” intelligent biomimetic matrices that per se initiate the ripple-like cascade of bone differentiation by induction without exogenously applied BMPs/OPs of the TGF-β supergene family. A comprehensive digital iconographic material presents the modified tissue engineering paradigm whereby the induction of bone formation is initiated by intelligent smart biomimetic matrices that per se initiate the induction of bone formation without the exogenous application of the soluble osteogenic molecular signals. The driving force of the intrinsic induction of bone formation by bioactive biomimetic matrices is the shape of the implanted substratum. The language of shape is the language of geometry; the language of geometry is the language of a sequence of repetitive concavities, which biomimetizes the remodelling cycle of the primate osteonic bone.
PMCID: PMC3083961  PMID: 21540997
Induction of bone formation; Bone morphogenetic proteins; Osteogenic proteins; Transforming growth factor-β proteins; Primates; Uroepithelial osteogenesis; Redundancy; Synergistic induction of bone formation; Biomimetic smart bioactive matrices
6.  Biomimicry of surfactant protein C 
Accounts of Chemical Research  2008;41(10):1409-1417.
Since the widespread use of exogenous lung surfactant to treat neonatal respiratory distress syndrome, premature infant survival and respiratory morbidity have dramatically improved. Despite the effectiveness of the animal-derived surfactant preparations, there still remain some concerns and difficulties associated with their use. This has prompted investigation into the creation of synthetic surfactant preparations. However, to date, no clinically used synthetic formulation is as effective as the natural material. This is largely because the previous synthetic formulations lacked analogues of the hydrophobic proteins of the lung surfactant system, SP-B and SP-C, which are critical functional constituents. As a result, recent investigation has turned towards the development of a new generation of synthetic, biomimetic surfactants that contain synthetic phospholipids along with a mimic of the hydrophobic protein portion of lung surfactant.
In this Account, we detail our efforts in creating accurate mimics of SP-C for use in a synthetic surfactant replacement therapy. Despite SP-C’s seemingly simple structure, the predominantly helical protein is extraordinarily challenging to work with given its extreme hydrophobicity and structural instability, which greatly complicates the creation of an effective SP-C analogue.
Drawing inspiration from Nature, two promising biomimetic approaches have led to the creation of rationally designed biopolymers that recapitulate many of SP-C’s molecular features. The first approach utilizes detailed SP-C structure-activity relationships and amino acid folding propensities to create a peptide-based analogue, SP-C33. In SP-C33, the problematic and metastable poly-valine helix is replaced with a structurally stable, poly-leucine helix and includes a well placed positive charge to prevent aggregation. SP-C33 is both structurally stable and eliminates the association propensity of the native protein. The second approach follows the same design considerations, but makes use of a non-natural, poly-N-substituted glycine or “peptoid” scaffold to circumvent the difficulties associated with SP-C. By incorporating unique, biomimetic side chains in a non-natural backbone, the peptoid mimic captures both SP-C’s hydrophobic patterning and helical secondary structure.
Despite the differences in structure, both SP-C33 and the SP-C peptoid mimic capture many requisite features of SP-C. In a surfactant environment, these analogues also replicate many of the key surface activities necessary for a functional biomimetic surfactant therapy while overcoming the difficulties associated with the natural protein. With improved stability, greater production potential, and elimination of possible pathogenic contamination, these biomimetic surfactant formulations offer the potential not only to improve the treatment of respiratory distress syndrome, but also the opportunity to treat other respiratory-related disorders.
PMCID: PMC3270935  PMID: 18834153
7.  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
8.  Research trends in biomimetic medical materials for tissue engineering: commentary 
We introduce our active experts’ communications and reviews (Part II) of 2015 Korea-China Joint Symposium on Biomimetic Medical Materials in Republic of Korea, which reflect their perspectives on current research trends of biomimetic medical materials for tissue regeneration in both Korea and China. The communications covered three topics of biomimetics, i.e., 1) hydrogel for therapeutics and extracellular matrix environments, 2) design of electrical polymers for communications between electrical sources and biological systems and 3) design of biomaterials for nerve tissue engineering. The reviews in the Part II will cover biomimetics of 3D bioprinting materials, surface modifications, nano/micro-technology as well as clinical aspects of biomaterials for cartilage.
PMCID: PMC4810519  PMID: 27026826
9.  Microarray analysis of the Escherichia coli response to CdTe-GSH Quantum Dots: understanding the bacterial toxicity of semiconductor nanoparticles 
BMC Genomics  2014;15(1):1099.
Most semiconductor nanoparticles used in biomedical applications are made of heavy metals and involve synthetic methods that require organic solvents and high temperatures. This issue makes the development of water-soluble nanoparticles with lower toxicity a major topic of interest. In a previous work our group described a biomimetic method for the aqueous synthesis of CdTe-GSH Quantum Dots (QDs) using biomolecules present in cells as reducing and stabilizing agents. This protocol produces nanoparticles with good fluorescent properties and less toxicity than those synthesized by regular chemical methods. Nevertheless, biomimetic CdTe-GSH nanoparticles still display some toxicity, so it is important to know in detail the effects of these semiconductor nanoparticles on cells, their levels of toxicity and the strategies that cells develop to overcome it.
In this work, the response of E. coli exposed to different sized-CdTe-GSH QDs synthesized by a biomimetic protocol was evaluated through transcriptomic, biochemical, microbiological and genetic approaches. It was determined that: i) red QDs (5 nm) display higher toxicity than green (3 nm), ii) QDs mainly induce expression of genes involved with Cd+2 stress (zntA and znuA) and tellurium does not contribute significantly to QDs-mediated toxicity since cells incorporate low levels of Te, iii) red QDs also induce genes related to oxidative stress response and membrane proteins, iv) Cd2+ release is higher in red QDs, and v) QDs render the cells more sensitive to polymyxin B.
Based on the results obtained in this work, a general model of CdTe-GSH QDs toxicity in E. coli is proposed. Results indicate that bacterial toxicity of QDs is mainly associated with cadmium release, oxidative stress and loss of membrane integrity. The higher toxicity of red QDs is most probably due to higher cadmium content and release from the nanoparticle as compared to green QDs. Moreover, QDs-treated cells become more sensitive to polymyxin B making these biomimetic QDs candidates for adjuvant therapies against bacterial infections.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-1099) contains supplementary material, which is available to authorized users.
PMCID: PMC4300170  PMID: 25496196
Toxicity mechanism; Transcriptomic response; Oxidative stress; Cadmium; Nanoparticles
10.  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
11.  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
12.  Structural Design and Sealing Performance Analysis of Biomimetic Sealing Ring 
In order to reduce the failure probability of rubber sealing rings in reciprocating dynamic seal, a new structure of sealing ring based on bionics was designed. The biomimetic ring has three concave ridges and convex bulges on each side which are very similar to earthworms. Bulges were circularly designed and sealing performances of the biomimetic ring in both static seal and dynamic seal were simulated by FEM. In addition, effects of precompression, medium pressure, speed, friction coefficient, and material parameters on sealing performances were discussed. The results show that von Mises stress of the biomimetic sealing ring distributed symmetrically in no-pressure static sealing. The maximum von Mises stress appears on the second bulge of the inner side. High contact stress concentrates on left bulges. Von Mises stress distribution becomes uneven under medium pressure. Both von Mises stress and contact stress increase when precompression, medium pressure, and rubber hardness increase in static sealing. Biomimetic ring can avoid rolling and distortion in reciprocating dynamic seal, and its working life is much longer than O-ring and rectangular ring. The maximum von Mises stress and contact stress increase with the precompression, medium pressure, rubber hardness, and friction coefficient in reciprocating dynamic seal.
PMCID: PMC4745432  PMID: 27019582
13.  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
14.  Adipose Stem Cell Coating of Biomimetic β-TCP Macrospheres by Use of Laboratory Centrifuge 
BioResearch Open Access  2013;2(1):67-71.
Biomimetic materials such as coral exoskeletons possess unique architectural structures with a uniform and interconnected porous network that can be beneficial as a scaffold material. In addition, these marine structures can be hydrothermally converted to calcium phosphates, while retaining the original structural properties. The ability of biomaterials to stimulate the local microenvironment is one of the main focuses in tissue engineering, and directly coating the scaffold with stem cells facilitates future potential applications in therapeutics and regenerative medicine. In this article we describe a new and simple method that uses a laboratory centrifuge to coat hydrothermally derived beta-tricalcium phosphate macrospheres from coral exoskeleton with stem cells. In this research the optimal seeding duration and speed were determined to be 1 min and 700 g. Scanning electron micrographs showed complete surface coverage by stem cells within 7 days of seeding. This study constitutes an important step toward achieving functional tissue-engineered implants by increasing our understanding of the influence of dynamic parameters on the efficiency and distribution of stem cell attachment to biomimetic materials and how stem cells interact with biomimetic materials.
PMCID: PMC3569929  PMID: 23515356
adipose-derived stem cells; biomimetic scaffolds; cell seeding; scaffold coating; stem cell coating
15.  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
16.  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
17.  Synthesis of Bone-like Nanocomposites Using Multiphosphorylated Peptides 
Acta biomaterialia  2014;10(5):2241-2249.
There is a great need for novel materials for mineralized tissue repair and regeneration. Two examples of such tissue, bone and dentin, are highly organized hierarchical nanocomposites in which mineral and organic phases interface at the molecular level. In contrast, current graft materials are either ceramic powders or physical blends of mineral and organic phases with mechanical properties far inferior to those of their target tissues. The objective of this study was to synthesize composite nanofibrils with highly integrated organic/inorganic phases inspired by the mineralized collagen fibrils of bone and dentin. Utilizing our understanding of bone and dentin biomineralization, we have first designed bioinspired peptides containing 3 Ser-Ser-Asp repeat motifs based on the highly phosphorylated protein, dentin phosphophoryn (DPP) found in dentin and alveolar bone. We demonstrate that up to 80% of serines in the peptide can be phosphorylated by casein kinases. We further tested the ability of these peptides to induce biomimetic calcium phosphate mineralization of collagen fibrils. Our mineralization studies have revealed that in the presence of these phosphorylated peptides, mineralized collagen fibrils structurally similar to the mineralized collagen fibrils of bone and dentin were formed. Our results demonstrate that using phosphorylated DPP-inspired peptides, we can successfully synthesize biomimetic composite nanofibrils with integrated organic and inorganic phases. These results provide the first step in the development of biomimetic nanostructured materials for mineralized tissue repair and regeneration using phosphopeptides.
PMCID: PMC4351712  PMID: 24434535
18.  Calcium powered phloem protein of SEO gene family “Forisome” functions in wound sealing and act as biomimetic smart materials 
Plant Signaling & Behavior  2014;9:e29438.
Forisomes protein belongs to SEO gene family and is unique to Fabaceae family. These proteins are located in sieve tubes of phloem and function to prevent loss of nutrient-rich photoassimilates, upon mechanical injury/wounding. Forisome protein is also known as ATP independent, mechanically active proteins. Despite the wealth of information role of forisome in plants are not yet fully understood. Recent reports suggest that forisomes protein can act as ideal model to study self assembly mechanism for development of nanotechnological devices like microfluidic system application in space exploration mission. Improvement in micro instrument is highly demanding and has been a key technology by NASA in future space exploration missions. Based on its physical parameters, forisome are found to be ideal biomimetic materials for micro fluidic system because the conformational shifts can be replicated in vitro and are fully reversible over large number of cycles. By the use of protein engineering forisome recombinant protein can be tailored. Due to its unique ability to convert chemical energy into mechanical energy forisome has received much attention. For nanotechnological application and handling biomolecules such as DNA, RNA, protein and cell as a whole microfluidic system will be the most powerful technology. The discovery of new biomimetic smart materials has been a key factor in development of space science and its requirements in such a challenging environment. The field of microfludic, particularly in terms of development of its components along with identification of new biomimetic smart materials, deserves more attention. More biophysical investigation is required to characterize it to make it more suitable under parameters of performance.
PMCID: PMC4205131  PMID: 25763691
ATP-independent motor protein; Fabaceae; phloem; microfluidics; P-protein bodies; sieve element occlusion; wound sealing
19.  Polymer Composition and Substrate Influences on the Adhesive Bonding of a Biomimetic, Cross-Linking Polymer 
Hierarchical biological materials such as bone, sea shells, and marine bioadhesives are providing inspiration for the assembly of synthetic molecules into complex structures. The adhesive system of marine mussels has been the focus of much attention in recent years. Several catechol-containing polymers are being developed to mimic the cross-linking of proteins containing 3,4-dihydroxyphenylalanine (DOPA) used by shellfish for sticking to rocks. Many of these biomimetic polymer systems have been shown to form surface coatings or hydrogels, however bulk adhesion is demonstrated less often. Developing adhesives requires addressing design issues including finding a good balance between cohesive and adhesive bonding interactions. Despite the growing number of mussel mimicking polymers, there has been little effort to generate structure-property relations and gain insights on what chemical traits give rise to the best glues. In this report, we examined the simplest of these biomimetic polymers, poly[(3,4-dihydroxystyrene)-co-styrene]. Pendant catechol groups (i.e., 3,4-dihydroxystyrene) were distributed throughout a polystyrene backbone. Several polymer derivatives were prepared, each with a different 3,4-dihyroxystyrene content. Bulk adhesion testing showed where the optimal middle ground of cohesive and adhesive bonding resides. Adhesive performance was benchmarked against commercial glues as well as the genuine material produced by live mussels. In the best case, bonding was similar to cyanoacrylate “Krazy” or “Super” glue. Performance was also examined using low (e.g., plastics) and high (e.g., metals, wood) energy surfaces. Adhesive bonding of poly[(3,4-dihydroxystyrene)-co-styrene] may be the strongest of reported mussel protein mimics. These insights should help us to design future biomimetic systems, thereby bringing us closer to development of bone cements, dental composites, and surgical glues.
PMCID: PMC3415564  PMID: 22582754
20.  Methods for Biomimetic Remineralization of Human Dentine: A Systematic Review 
This study aimed to review the laboratory methods on biomimetic remineralization of demineralized human dentine. A systematic search of the publications in the PubMed, TRIP, and Web of Science databases was performed. Titles and abstracts of initially identified publications were screened. Clinical trials, reviews, non-English articles, resin-dentine interface studies, hybrid layer studies, hybrid scaffolds studies, and irrelevant studies were excluded. The remaining papers were retrieved with full texts. Manual screening was conducted on the bibliographies of remaining papers to identify relevant articles. A total of 716 studies were found, and 690 were excluded after initial screening. Two articles were identified from the bibliographies of the remaining papers. After retrieving the full text, 23 were included in this systematic review. Sixteen studies used analogues to mimic the functions of non-collagenous proteins in biomineralization of dentine, and four studies used bioactive materials to induce apatite formation on demineralized dentine surface. One study used zinc as a bioactive element, one study used polydopamine, and another study constructed an agarose hydrogel system for biomimetic mineralization of dentine. Many studies reported success in biomimetic mineralization of dentine, including the use of non-collagenous protein analogues, bioactive materials, or elements and agarose hydrogel system.
PMCID: PMC4394438  PMID: 25739078
biomimetic; remineralization; dentine; non-collagenous proteins
21.  Multiscale deformations lead to high toughness and circularly polarized emission in helical nacre-like fibres 
Nature Communications  2016;7:10701.
Nacre-like composites have been investigated typically in the form of coatings or free-standing sheets. They demonstrated remarkable mechanical properties and are used as ultrastrong materials but macroscale fibres with nacre-like organization can improve mechanical properties even further. The fiber form or nacre can, simplify manufacturing and offer new functional properties unknown yet for other forms of biomimetic materials. Here we demonstrate that nacre-like fibres can be produced by shear-induced self-assembly of nanoplatelets. The synergy between two structural motifs—nanoscale brick-and-mortar stacking of platelets and microscale twisting of the fibres—gives rise to high stretchability (>400%) and gravimetric toughness (640 J g−1). These unique mechanical properties originate from the multiscale deformation regime involving solid-state self-organization processes that lead to efficient energy dissipation. Incorporating luminescent CdTe nanowires into these fibres imparts the new property of mechanically tunable circularly polarized luminescence. The nacre-like fibres open a novel technological space for optomechanics of biomimetic composites, while their continuous spinning methodology makes scalable production realistic.
The mechanical properties and hierarchical structure of nacre have been widely investigated as a biomimetic template for applications. Here, the authors demonstrate that nacre-like fibres made from nanoplatelets and polymers show exceptional stretchability and toughness.
PMCID: PMC4770083  PMID: 26907888
22.  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
23.  Enhanced Osteogenicity of Bioactive Composites with Biomimetic Treatment 
BioMed Research International  2014;2014:207676.
Purpose. This study aimed to explore if initiation of biomimetic apatite nucleation can be used to enhance osteoblast response to biodegradable tissue regeneration composite membranes. Materials and Methods. Bioactive thermoplastic composites consisting of poly(ε-caprolactone/DL-lactide) and bioactive glass (BAG) were prepared at different stages of biomimetic calcium phosphate deposition by immersion in simulated body fluid (SBF). The modulation of the BAG dissolution and the osteogenic response of rat mesenchymal stem cells (MSCs) were analyzed. Results. SBF treatment resulted in a gradual calcium phosphate deposition on the composites and decreased BAG reactivity in the subsequent cell cultures. Untreated composites and composites covered by thick calcium phosphate layer (14 days in SBF) expedited MSC mineralization in comparison to neat polymers without BAG, whereas other osteogenic markers—alkaline phosphatase activity, bone sialoprotein, and osteocalcin expression—were initially decreased. In contrast, surfaces with only small calcium phosphate aggregates (five days in SBF) had similar early response than neat polymers but still demonstrated enhanced mineralization. Conclusion. A short biomimetic treatment enhances osteoblast response to bioactive composite membranes.
PMCID: PMC4000935  PMID: 24812608
24.  Magnesium-Containing Nanostructured Hybrid Scaffolds for Enhanced Dentin Regeneration 
Tissue Engineering. Part A  2014;20(17-18):2422-2433.
Dental caries is one of the most prevalent chronic diseases in the United States, affecting 92% of adults aged 20–64 years. Scaffold-based tissue engineering represents a promising strategy to replace damaged dental structures and restore their biological functions. Current single-component scaffolding materials used for dental tissue regeneration, however, cannot provide the proper microenvironment for dental stem/progenitor cell adhesion, proliferation, and differentiation; new biomimetic hybrid scaffolds are needed to promote better dental tissue formation. In this work, we developed a biomimetic approach to prepare three-dimensional (3D) nanofibrous gelatin/magnesium phosphate (NF-gelatin/MgP) hybrid scaffolds. These scaffolds not only mimic the nanostructured architecture and the chemical composition of natural dentin matrices but also constantly present favorable chemical signals (Mg ions) to dental pulp stem cells (DPSCs), thus providing a desirable microenvironment to facilitate DPSC proliferation, differentiation, and biomineralization. Synthesized hybrid NF-gelatin/MgP possesses natural extracellular matrix (ECM)-like architecture, high porosity, high pore interconnectivity, well-defined pore size, and controlled Mg ion release from the scaffold. Adding MgP into NF-gelatin also increased the mechanical strength of the hybrid scaffold. The sustained release of Mg ions from the NF-gelatin/MgP (MgP=10% wt/wt) scaffold significantly enhanced the proliferation, differentiation, and biomineralization of human DPSCs in vitro. The alkaline phosphatase (ALP) activity and the gene expressions for odontogenic differentiation (collagen I [Col I], ALP, osteocalcin [OCN], dentin sialophosphoprotein [DSPP], and dentin matrix protein 1 [DMP1]) were all significantly higher (p<0.05) in the NF-gelatin/MgP group than in the NF-gelatin group. Those results were further confirmed by hematoxylin and eosin (H&E) and von Kossa staining, as shown by greater ECM secretion and mineral deposition in the hybrid scaffold. Consistent with the in vitro study, the DPSCs/NF-gelatin/MgP constructs produced greater ECM deposition, hard tissue formation, and expression of marker proteins (DSPP, DMP1, Col I) for odontogenic differentiation than did the DPSCs/NF-gelatin after 5 weeks of ectopic implantation in rude mice. The controlled release of metallic ions from biomimetic nanostructured hybrid scaffolds, therefore, is a promising approach to enhancing the biological capability of the scaffolds for dental tissue regeneration.
PMCID: PMC4161063  PMID: 24593189
25.  ENDOXY - Development of a Biomimetic Oxygenator-Test-Device 
PLoS ONE  2015;10(12):e0142961.
This study focusses on the development of a biomimetic oxygenator test device. Due to limited biocompatibility, current oxygenators do not allow mid- to long-term therapy. Tissue engineering uses autologous cell sources to overcome the immunogenic barriers of biomaterials. Surface coating with endothelial cells might improve hemocompatibility and thus prevent immunogenic reactions of the body. In this study this concept is applied to endothelialise a gas-permeable membrane to develop a biomimetic oxygenator test-device (ENDOXY).
ENDOXY—a multifunctional test-system was developed to endothelialise a gas-permeable membrane suitable for cell culture and to test the cell retention under shear stress and to measure gas transfer through it.
Successful endothelialisation of the membrane was achieved and cells showed characteristic endothelial morphologies. They stained positive for endothelial markers. The number of cells aligned with shear stress and cell retention after blood perfusing experiments was high. Gas transfer is observed via uncoated and endothelialised membranes.
The study showed promising results with regard to system design, endothelialisation, and cell retention under shear stress conditions. It strongly encourages further research into the system by testing different membrane materials to design a biomimetic membrane surface and pave way for a fully hemocompatible oxygenator.
PMCID: PMC4684320  PMID: 26682907

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