Engineering Interfacial Integrity with Hydrolytic-Resistant, Self-Reinforcing Dentin Adhesive.

The leading cause of composite restoration failure is secondary caries, and although caries is a multifactorial problem, weak, damage-prone adhesives play a pivotal role in the high susceptibility of composite restorations to secondary caries. Our group has developed synthetic resins that capitalize on free-radical polymerization and sol-gel reactions to provide dental adhesives with enhanced properties. The resins contain γ-methacryloxypropyltrimethoxysilane (MPS) as the Si-based compound. This study investigated the properties of methacrylate-based resins containing methacryloxymethyltrimethoxysilane (MMeS) as a short-chain alternative. The degree of conversion (DC), polymerization kinetics, water sorption, mechanical properties, and leachates of MMeS- and MPS-resins with 55 and 30 wt% BisGMA-crosslinker were determined. The formulations were used as model adhesives, and the adhesive/dentin (a/d) interfaces were analyzed using chemometrics-assisted micro-Raman spectroscopy. The properties of the 55 wt% formulations were comparable. In the 30 wt% BisGMA formulations, the MMeS-resin exhibited faster polymerization, lower DC, reduced leachates, and increased storage and loss moduli, glass transition (Tg), crosslink density, and heterogeneity. The spectroscopic results indicated a comparable spatial distribution of resin, mineralized, and demineralized dentin across the a/d interfaces. The hydrolytically stable experimental short-chain-silane-monomer dental adhesive provides enhanced mechanical properties through autonomous strengthening and offers a promising strategy for the development of restorative dental materials with extended service life.

Engineered Peptides Enable Biomimetic Route for Collagen Intrafibrillar Mineralization.

Overcoming the short lifespan of current dental adhesives remains a significant clinical need. Adhesives rely on formation of the hybrid layer to adhere to dentin and penetrate within collagen fibrils. However, the ability of adhesives to achieve complete enclosure of demineralized collagen fibrils is recognized as currently unattainable. We developed a peptide-based approach enabling collagen intrafibrillar mineralization and tested our hypothesis on a type-I collagen-based platform. Peptide design incorporated collagen-binding and remineralization-mediating properties using the domain structure conservation approach. The structural changes from representative members of different peptide clusters were generated for each functional domain. Common signatures associated with secondary structure features and the related changes in the functional domain were investigated by attenuated total reflectance Fourier-transform infrared (ATR-FTIR) and circular dichroism (CD) spectroscopy, respectively. Assembly and remineralization properties of the peptides on the collagen platforms were studied using atomic force microscopy (AFM). Mechanical properties of the collagen fibrils remineralized by the peptide assemblies was studied using PeakForce-Quantitative Nanomechanics (PF-QNM)-AFM. The engineered peptide was demonstrated to offer a promising route for collagen intrafibrillar remineralization. This approach offers a collagen platform to develop multifunctional strategies that combine different bioactive peptides, polymerizable peptide monomers, and adhesive formulations as steps towards improving the long-term prospects of composite resins.

Autonomous-Strengthening Adhesive Provides Hydrolysis-Resistance and Enhanced Mechanical Properties in Wet Conditions.

The low-viscosity adhesive that is used to bond composite restorative materials to the tooth is readily damaged by acids, enzymes, and oral fluids. Bacteria infiltrate the resulting gaps at the composite/tooth interface, demineralize the tooth, and further erode the adhesive. This paper presents the preparation and characterization of a low-crosslink-density hydrophilic adhesive that capitalizes on sol-gel reactions and free-radical polymerization to resist hydrolysis and provide enhanced mechanical properties in wet environments. Polymerization behavior, water sorption, and leachates were investigated. Dynamic mechanical analyses (DMA) were conducted using water-saturated adhesives to mimic load transfer in wet conditions. Data from all tests were analyzed using appropriate statistical tests (α = 0.05). The degree of conversion was comparable for experimental and control adhesives at 88.3 and 84.3%, respectively. HEMA leachate was significantly lower for the experimental (2.9 wt%) compared to control (7.2 wt%). After 3 days of aqueous aging, the storage and rubbery moduli and the glass transition temperature of the experimental adhesive (57.5MPa, 12.8MPa, and 38.7 °C, respectively) were significantly higher than control (7.4MPa, 4.3 MPa, and 25.9 °C, respectively). The results indicated that the autonomic sol-gel reaction continues in the wet environment, leading to intrinsic reinforcement of the polymer network, improved hydrolytic stability, and enhanced mechanical properties.

Combining genetic algorithm with machine learning strategies for designing potent antimicrobial peptides.

BACKGROUND: Current methods in machine learning provide approaches for solving challenging, multiple constraint design problems. While deep learning and related neural networking methods have state-of-the-art performance, their vulnerability in decision making processes leading to irrational outcomes is a major concern for their implementation. With the rising antibiotic resistance, antimicrobial peptides (AMPs) have increasingly gained attention as novel therapeutic agents. This challenging design problem requires peptides which meet the multiple constraints of limiting drug-resistance in bacteria, preventing secondary infections from imbalanced microbial flora, and avoiding immune system suppression. AMPs offer a promising, bioinspired design space to targeting antimicrobial activity, but their versatility also requires the curated selection from a combinatorial sequence space. This space is too large for brute-force methods or currently known rational design approaches outside of machine learning. While there has been progress in using the design space to more effectively target AMP activity, a widely applicable approach has been elusive. The lack of transparency in machine learning has limited the advancement of scientific knowledge of how AMPs are related among each other, and the lack of general applicability for fully rational approaches has limited a broader understanding of the design space. METHODS: Here we combined an evolutionary method with rough set theory, a transparent machine learning approach, for designing antimicrobial peptides (AMPs). Our method achieves the customization of AMPs using supervised learning boundaries. Our system employs in vitro bacterial assays to measure fitness, codon-representation of peptides to gain flexibility of sequence selection in DNA-space with a genetic algorithm and machine learning to further accelerate the process. RESULTS: We use supervised machine learning and a genetic algorithm to find a peptide active against S. epidermidis, a common bacterial strain for implant infections, with an improved aggregation propensity average for an improved ease of synthesis. CONCLUSIONS: Our results demonstrate that AMP design can be customized to maintain activity and simplify production. To our knowledge, this is the first time when codon-based genetic algorithms combined with rough set theory methods is used for computational search on peptide sequences.

Reconfigurable Dual Peptide Tethered Polymer System Offers a Synergistic Solution for Next Generation Dental Adhesives.

Resin-based composite materials have been widely used in restorative dental materials due to their aesthetic, mechanical, and physical properties. However, they still encounter clinical shortcomings mainly due to recurrent decay that develops at the composite-tooth interface. The low-viscosity adhesive that bonds the composite to the tooth is intended to seal this interface, but the adhesive seal is inherently defective and readily damaged by acids, enzymes, and oral fluids. Bacteria infiltrate the resulting gaps at the composite-tooth interface and bacterial by-products demineralize the tooth and erode the adhesive. These activities lead to wider and deeper gaps that provide an ideal environment for bacteria to proliferate. This complex degradation process mediated by several biological and environmental factors damages the tooth, destroys the adhesive seal, and ultimately, leads to failure of the composite restoration. This paper describes a co-tethered dual peptide-polymer system to address composite-tooth interface vulnerability. The adhesive system incorporates an antimicrobial peptide to inhibit bacterial attack and a hydroxyapatite-binding peptide to promote remineralization of damaged tooth structure. A designer spacer sequence was incorporated into each peptide sequence to not only provide a conjugation site for methacrylate (MA) monomer but also to retain active peptide conformations and enhance the display of the peptides in the material. The resulting MA-antimicrobial peptides and MA-remineralization peptides were copolymerized into dental adhesives formulations. The results on the adhesive system composed of co-tethered peptides demonstrated both strong metabolic inhibition of S. mutans and localized calcium phosphate remineralization. Overall, the result offers a reconfigurable and tunable peptide-polymer hybrid system as next-generation adhesives to address composite-tooth interface vulnerability.

Antimicrobial peptide similarity and classification through rough set theory using physicochemical boundaries.

BACKGROUND: Antimicrobial peptides attract considerable interest as novel agents to combat infections. Their long-time potency across bacteria, viruses and fungi as part of diverse innate immune systems offers a solution to overcome the rising concerns from antibiotic resistance. With the rapid increase of antimicrobial peptides reported in the databases, peptide selection becomes a challenge. We propose similarity analyses to describe key properties that distinguish between active and non-active peptide sequences building upon the physicochemical properties of antimicrobial peptides. We used an iterative supervised machine learning approach to classify active peptides from inactive peptides with low false discovery rates in a relatively short computational search time. RESULTS: By generating explicit boundaries, our method defines new categories of active and inactive peptides based on their physicochemical properties. Consequently, it describes physicochemical characteristics of similarity among active peptides and the physicochemical boundaries between active and inactive peptides in a single process. To build the similarity boundaries, we used the rough set theory approach; to our knowledge, this is the first time that this approach has been used to classify peptides. The modified rough set theory method limits the number of values describing a boundary to a user-defined limit. Our method is optimized for specificity over selectivity. Noting that false positives increase activity assays while false negatives only increase computational search time, our method provided a low false discovery rate. Published datasets were used to compare our rough set theory method to other published classification methods and based on this comparison, we achieved high selectivity and comparable sensitivity to currently available methods. CONCLUSIONS: We developed rule sets that define physicochemical boundaries which allow us to directly classify the active sequences from inactive peptides. Existing classification methods are either sequence-order insensitive or length-dependent, whereas our method generates the rule sets that combine order-sensitive descriptors with length-independent descriptors. The method provides comparable or improved performance to currently available methods. Discovering the boundaries of physicochemical properties may lead to a new understanding of peptide similarity.

Computer-aided Molecular Design of Water Compatible Visible Light Photosensitizers for Dental Adhesive.

Dental adhesive resin undergoes phase separation during its infiltration through the wet demineralized dentin and it has been observed previously that the hydrophilic-rich phase is a vulnerable region for failure due to the lack of photo-polymerization and crosslinking density. The lack of photo-polymerization is mostly due to the partitioning of photo-initiators in low concentrations within this phase. Here, a computational approach has been employed to design candidate water compatible visible light photosensitizers which could improve the photo-polymerization of the hydrophilic-rich phase. This study is an extension of our previous work. QSPRs were developed for properties related to the photo-polymerization reaction of the adhesive monomers and hydrophilicity of the photosensitizer using connectivity indices as descriptors. QSPRs and structural constraints were formulated into an optimization problem which was solved stochastically via Tabu Search. Four candidate photosensitizer molecules have been proposed here which have the iminium ion as a common feature.

Effect of Partition of Photo-initiator Components and Addition of Iodonium Salt on the Photopolymerization of Phase-Separated Dental Adhesive.

The polymerization kinetics of physically separated hydrophobic- and hydrophilic-rich phases of a model dental adhesive have been investigated. The two phases were prepared from neat resin containing 2-hydroxyethyl methacrylate (HEMA) and bisphenol A glycerolate dimethacrylate (BisGMA) in the ratio of 45:55 (wt/wt). Neat resins containing various combinations of popular photo-initiating compounds, e.g., camphoquinone (CQ), ethyl 4-(dimethylamino)benzoate (EDMAB), 2-(dimethylamino)ethyl methacrylate (DMAEMA) and diphenyliodonium hexafluorophosphate (DPIHP) were prepared. To obtain the two phases 33 wt% of deuterium oxide (D2O) was added to the neat resins. This amount of D2O exceeded the miscibility limit for the resins. The concentration of each component of the photo-initiating system in the two phases was quantified by HPLC. When combined with CQ, DMAEMA is less efficient as a co-initiator compared to EDMAB. The addition of DPIHP as the third component into either CQ/EDMAB or CQ/DMAEMA photo-initiating systems leads to comparable performance in both the hydrophobic- and hydrophilic-rich phases. The addition of the iodonium salt significantly improved the photopolymerization of the hydrophilic-rich phase; the hydrophilic-rich phase exhibited extremely poor polymerization when the iodonium salt was not included in the formulation. The partition concentration of EDMAB in the hydrophilic-rich phase was significantly lower than that of DMAEMA or DPIHP. This study indicates the need for a combination of hydrophobic/hydrophilic photosensitizer and addition of iodonium salt to improve polymerization within the hydrophilic-rich phase of the dental adhesive.

Synthesis and evaluation of a novel co-initiator for dentin adhesives: polymerization kinetics and leachables study.

A new tertiary amine co-initiator (TUMA) containing three methacrylate-urethane groups was synthesized for application in dentin adhesives. The photopolymerization kinetics and leaching of unreacted components from methacrylate-based dental polymers formulated with this new co-initiator were determined. The newly synthesize co-initiator showed good chemical stability and decreased amine release from the initiator system. This study provides important information for the future development of biocompatible dentin adhesives/composites.

Genetic disease risks of under-represented founder populations in New York City.

The detection of founder pathogenic variants, those observed in high frequency only in a group of individuals with increased inter-relatedness, can help improve delivery of health care for that community. We identified 16 groups with shared ancestry, based on genomic segments that are shared through identity by descent (IBD), in New York City using the genomic data of 25,366 residents from the All Of Us Research Program and the Mount Sinai BioMe biobank. From these groups we defined 8 as founder populations, mostly communities currently under-represented in medical genomics research, such as Puerto Rican, Garifuna and Filipino/Pacific Islanders. The enrichment analysis of ClinVar pathogenic or likely pathogenic (P/LP) variants in each group identified 202 of these damaging variants across the 8 founder populations. We confirmed disease-causing variants previously reported to occur at increased frequencies in Ashkenazi Jewish and Puerto Rican genetic ancestry groups, but most of the damaging variants identified have not been previously associated with any such founder populations, and most of these founder populations have not been described to have increased prevalence of the associated rare disease. Twenty-five of 51 variants meeting Tier 2 clinical screening criteria (1/100 carrier frequency within these founder groups) have never previously been reported. We show how population structure studies can provide insights into rare diseases disproportionately affecting under-represented founder populations, delivering a health care benefit but also a potential source of stigmatization of these communities, who should be part of the decision-making about implementation into health care delivery.

Effect of EDTA Gel on Residual Subgingival Calculus and Biofilm: An In Vitro Pilot Study.

BACKGROUND: Residual calculus, following scaling and root planing (SRP), is associated with persistent inflammation and the progression of periodontitis. This study examined the effects of a 24% neutral ethylenediaminetetraacetic acid (EDTA) gel on subgingival calculus and biofilms. METHODS: Eleven single-rooted teeth extracted because of severe periodontal disease were randomly assigned to the following treatment groups: (1) three teeth served as untreated controls; (2) three teeth were treated by scaling and root planing (SRP) only; and (3) three teeth were treated by SRP + EDTA. The remaining two teeth, one SRP only and the other SRP + EDTA were designated for energy-dispersive X-ray spectroscopy (EDS) analysis. EDTA gel was placed on the SRP surface for 2 min and then burnished with a sterile cotton pellet. RESULTS: SRP + EDTA treated specimens exhibited severely damaged biofilm and the disruption of the extracellular polymeric matrix. EDS scans of the smear layer and calculus featured reductions in the Weight % and Atomic % for N, F, Na, and S and increases in Mg, P, and Ca. CONCLUSIONS: A 25% neutral EDTA gel was applied after SRP severely disrupted the residual biofilm and altered the character of dental calculus and the smear layer as shown by reductions in the Weight % and Atomic % for N, F, Na, and S and increases in Mg, P, and Ca.

Designing Collagen-Binding Peptide with Enhanced Properties Using Hydropathic Free Energy Predictions.

Collagen is fundamental to a vast diversity of health functions and potential therapeutics. Short peptides targeting collagen are attractive for designing modular systems for site-specific delivery of bioactive agents. Characterization of peptide-protein binding involves a larger number of potential interactions that require screening methods to target physiological conditions. We build a hydropathy-based free energy estimation tool which allows quick evaluation of peptides binding to collagen. Previous studies showed that pH plays a significant role in collagen structure and stability. Our design tool enables probing peptides for their collagen-binding property across multiple pH conditions. We explored binding features of currently known collagen-binding peptides, collagen type I alpha chain 2 sense peptide (TKKTLRT) and decorin LRR-10 (LRELHLNNN). Based on these analyzes, we engineered a collagen-binding peptide with enhanced properties across a large pH range in contrast to LRR-10 pH dependence. To validate our predictions, we used a quantum-dots-based binding assay to compare the coverage of the peptides on type I collagen. The predicted peptide resulted in improved collagen binding. Hydropathy of the peptide-protein pair is a promising approach to finding compatible pairings with minimal use of computational resources, and our method allows for quick evaluation of peptides for binding to other proteins. Overall, the free-energy-based tool provides an alternative computational screening approach that impacts protein interaction search methods.

Diffusion coefficients of water and leachables in methacrylate-based crosslinked polymers using absorption experiments.

The diffusion of water into dentin adhesive polymers and leaching of unpolymerized monomer from the adhesive are linked to their mechanical softening and hydrolytic degradation. Therefore, diffusion coefficient data are critical for the mechanical design of these polymeric adhesives. In this study, diffusion coefficients of water and leachables were obtained for sixteen methacrylate-based crosslinked polymers using absorption experiments. The experimental mass change data was interpreted using numerical solution of the two-dimensional diffusion equations. The calculated diffusion coefficients varied from 1.05 × 10(-8) cm(2)/sec (co-monomer TMTMA) to 3.15 × 10(-8) cm(2)/sec (co-monomer T4EGDMA). Correlation of the diffusion coefficients with crosslink density and hydrophilicity showed an inverse trend (R(2) = 0.41). The correlation of diffusion coefficient with crosslink density and hydrophilicity are closer for molecules differing by simple repeat units (R(2) = 0.95). These differences in the trends reveal mechanisms of interaction of the diffusing water with the polymer structure.

Engineering peptide-polymer hybrids for targeted repair and protection of cervical lesions.

By 2060, nearly 100 million people in the U.S. will be over age 65 years. One-third of these older adults will have root caries, and nearly 80% will have dental erosion. These conditions can cause pain and loss of tooth structure that interfere with eating, speaking, sleeping, and quality of life. Current treatments for root caries and dental erosion have produced unreliable results. For example, the glass-ionomer-cement or composite-resin restorations used to treat these lesions have annual failure rates of 44% and 17%, respectively. These limitations and the pressing need to treat these conditions in the aging population are driving a focus on microinvasive strategies, such as sealants and varnishes. Sealants can inhibit caries on coronal surfaces, but they are ineffective for root caries. For healthy, functionally independent elders, chlorhexidine varnish applied every 3 months inhibits root caries, but this bitter-tasting varnish stains the teeth. Fluoride gel inhibits root caries, but requires prescriptions and daily use, which may not be feasible for some older patients. Silver diamine fluoride can both arrest and inhibit root caries but stains the treated tooth surface black. The limitations of current approaches and high prevalence of root caries and dental erosion in the aging population create an urgent need for microinvasive therapies that can: (a) remineralize damaged dentin; (b) inhibit bacterial activity; and (c) provide durable protection for the root surface. Since cavitated and non-cavitated root lesions are difficult to distinguish, optimal approaches will treat both. This review will explore the multi-factorial elements that contribute to root surface lesions and discuss a multi-pronged strategy to both repair and protect root surfaces. The strategy integrates engineered peptides, novel polymer chemistry, multi-scale structure/property characterization and predictive modeling to develop a durable, microinvasive treatment for root surface lesions.

Peptide-Enabled Nanocomposites Offer Biomimetic Reconstruction of Silver Diamine Fluoride-Treated Dental Tissues.

Caries is the most ubiquitous infectious disease of mankind, and early childhood caries (ECC) is the most prevalent chronic disease in children worldwide, with the resulting destruction of the teeth recognized as a global health crisis. Recent the United States Food and Drug Administration (FDA) approval for the use of silver diamine fluoride (SDF) in dentistry offers a safe, accessible, and inexpensive approach to arrest caries progression in children with ECC. However, discoloration, i.e., black staining, of demineralized or cavitated surfaces treated with SDF has limited its widespread use. Targeting SDF-treated tooth surfaces, we developed a biohybrid calcium phosphate nanocomposite interface building upon the self-assembly of synthetic biomimetic peptides. Here, an engineered bifunctional peptide composed of a silver binding peptide (AgBP) is covalently joined to an amelogenin derived peptide (ADP). The AgBP provides anchoring to the SDF-treated tooth tissue, while the ADP promotes rapid formation of a calcium phosphate isomorph nanocomposite mimicking the biomineralization function of the amelogenin protein. Our results demonstrate that the bifunctional peptide was effective in remineralizing the biomineral destroyed by caries on the SDF-treated tooth tissues. The proposed engineered peptide approach offers a biomimetic path for remineralization of the SDF-treated tissues producing a calcium phosphate nanocomposite interface competent to be restored using commonly available adhesive dental composites.

Community health workers' critical role in trust building between the medical system and communities of color.

The authors interrogate elements of routine medical practice in New York City to argue for reforms of hospital culture through relational trust-building capabilities of community health workers.

Effect of mucoprotein on the bond strength of resin composite to human dentin.

The purpose of this study was to test the bond strength and analyze the morphology of the dentin-adhesive interface of two etch and rinse and two self-etch adhesive systems with two kinds of artificial saliva (with and without 450 mg/L mucin) contamination under different conditions of decontaminating the interface. Bonded specimens were sectioned perpendicularly to the bonded surface in 1-mm thick slabs. These 1-mm thick slabs were remounted in acrylic blocks and sectioned in sticks perpendicular to the bonding interfaces with a 1-mm(2) area. Nine specimens from each condition were tested after 24 h on a testing machine (Instron) at a speed of 0.5 mm/min for a total of 360 specimens. Mean and standard deviations of bond strength (MPa) were calculated. ANOVA showed significant differences as well as Fisher's PLSD intervals (p < 0.05). The following values are the results for different groups: Control group 34-60 MPa, saliva without mucin 0-52 MPa, and saliva with mucin 0-57 MPa. Failure sites were mixed and adhesive failure was common for the low bond strength results. P&BNT with ideal conditions and following the manufacturer's instructions (control) had the highest bond strengths and the dentin-adhesive interface exhibited an ideal morphology of etch-and-rinse system. SEM gave complementary visual evidence of the effect in the dentin/adhesive interface structure with some contaminated conditions compared with their respective control groups. This in vitro artificial saliva model with and without mucin showed that an organic component of saliva could increase or decrease the bond strength depending on the specific bonding agent and decontamination procedure.

Probing the mineralized tissue-adhesive interface for tensile nature and bond strength.

The mechanical performance of the dentin-adhesive interface contributes significantly to the failure of dental composite restorations. Rational material design can lead to enhanced mechanical performance, but this requires accurate characterization of the mechanical behavior at the dentin-adhesive interface. The mechanical performance of the interface is typically characterized using bond strength tests, such as the micro-tensile test. These tests are plagued by multiple limitations including large variations in the test results. The challenges associated with conventional tensile tests limit our ability to unravel the complex relationships that affect mechanical behavior at the dentin-adhesive interface. This study used the diametral compression test to overcome the challenges inherent in conventional bond strength tests. The bovine femur cortical bone tissue was considered as a surrogate material (the mineralized tissue) for human dentin. Two different adhesive formulations, which differed by means of their self-strengthening properties, were studied. The tensile behavior of the mineralized tissue, the adhesive polymer, and the bond strength of the mineralized tissue - adhesive interface was determined using the diametral compression test. The diametral compression test improved the repeatability for both the tensile and bond strength tests. The rate dependent mechanical behavior was observed for both single material and interfacial material systems. The tensile strength and bond strength of the mineralized tissue-adhesive interface was greater for the self-strengthening formulation as compared to the control.

Chemometrics-Assisted Raman Spectroscopy Characterization of Tunable Polymer-Peptide Hybrids for Dental Tissue Repair.

The interfaces that biological tissues form with biomaterials are invariably defective and frequently the location where failure initiates. Characterizing the phenomena that lead to failure is confounded by several factors including heterogeneous material/tissue interfaces. To seamlessly analyze across these diverse structures presents a wealth of analytical challenges. This study aims to develop a molecular-level understanding of a peptide-functionalized adhesive/collagen hybrid biomaterial using Raman spectroscopy combined with chemometrics approach. An engineered hydroxyapatite-binding peptide (HABP) was copolymerized in dentin adhesive and dentin was demineralized to provide collagen matrices that were partially infiltrated with the peptide-functionalized adhesive. Partial infiltration led to pockets of exposed collagen-a condition that simulates defects in adhesive/dentin interfaces. The spectroscopic results indicate that co-polymerizable HABP tethered to the adhesive promoted remineralization of the defects. The spatial distribution of collagen, adhesive, and mineral as well as crystallinity of the mineral across this heterogeneous material/tissue interface was determined using micro-Raman spectroscopy combined with chemometrics approach. The success of this combined approach in the characterization of material/tissue interfaces stems from its ability to extract quality parameters that are related to the essential and relevant portions of the spectral data, after filtering out noise and non-relevant information. This ability is critical when it is not possible to separate components for analysis such as investigations focused on, in situ chemical characterization of interfaces. Extracting essential information from complex bio/material interfaces using data driven approaches will improve our understanding of heterogeneous material/tissue interfaces. This understanding will allow us to identify key parameters within the interfacial micro-environment that should be harnessed to develop durable biomaterials.

Bioinspired multifunctional adhesive system for next generation bio-additively designed dental restorations.

Resin-based composite has overtaken dental amalgam as the most popular material for the repair of lost or damaged tooth structure. In spite of the popularity, the average composite lifetime is about half that of amalgam restorations. The leading cause of composite-restoration failure is decay at the margin where the adhesive is applied. The adhesive is intended to seal the composite/tooth interface, but the adhesive seal to dentin is fragile and readily degraded by acids, enzymes and other oral fluids. The inherent weakness of this material system is attributable to several factors including the lack of antimicrobial properties, remineralization capabilities and durable mechanical performance - elements that are central to the integrity of the adhesive/dentin (a/d) interfacial seal. Our approach to this problem offers a transition from a hybrid to a biohybrid structure. Discrete peptides are tethered to polymers to provide multi-bio-functional adhesive formulations that simultaneously achieve antimicrobial and remineralization properties. The bio-additive materials design combines several functional properties with the goal of providing an adhesive that will serve as a durable barrier to recurrent decay at the composite/tooth interface. This article provides an overview of our multi-faceted approach which uses peptides tethered to polymers and new polymer chemistries to achieve the next generation adhesive system - an adhesive that provides antimicrobial properties, repair of defective dentin and enhanced mechanical performance.