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1.
Int J Mol Sci ; 22(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207218

RESUMO

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.


Assuntos
Antibacterianos/química , Cimentos Dentários/química , Proteínas Citotóxicas Formadoras de Poros/química , Antibacterianos/farmacologia , Resinas Compostas/química , Resinas Compostas/farmacologia , Cimentos Dentários/farmacologia , Metacrilatos/química , Proteínas Citotóxicas Formadoras de Poros/farmacologia , Streptococcus mutans/efeitos dos fármacos , Remineralização Dentária/métodos
2.
J Orthop Res ; 39(7): 1368-1382, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33751642

RESUMO

Meniscal injuries represent one of the most common orthopedic injuries. The most frequent treatment is partial resection of the meniscus, or meniscectomy, which can affect joint mechanics and health. For this reason, the field has shifted gradually towards suture repair, with the intent of preservation of the tissue. "Save the Meniscus" is now a prolific theme in the field; however, meniscal repair can be challenging and ineffective in many scenarios. The objectives of this review are to present the current state of surgical management of meniscal injuries and to explore current approaches being developed to enhance meniscal repair. Through a systematic literature review, we identified meniscal tear classifications and prevalence, approaches being used to improve meniscal repair, and biological- and material-based systems being developed to promote meniscal healing. We found that biologic augmentation typically aims to improve cellular incorporation to the wound site, vascularization in the inner zones, matrix deposition, and inflammatory relief. Furthermore, materials can be used, both with and without contained biologics, to further support matrix deposition and tear integration, and novel tissue adhesives may provide the mechanical integrity that the meniscus requires. Altogether, evaluation of these approaches in relevant in vitro and in vivo models provides new insights into the mechanisms needed to salvage meniscal tissue, and along with regulatory considerations, may justify translation to the clinic. With the need to restore long-term function to injured menisci, biologists, engineers, and clinicians are developing novel approaches to enhance the future of robust and consistent meniscal reparative techniques.


Assuntos
Artroplastia/métodos , Produtos Biológicos/uso terapêutico , Lesões do Menisco Tibial/cirurgia , Tecidos Suporte , Animais , Modelos Animais de Doenças , Humanos
3.
Biochemistry ; 41(25): 8134-42, 2002 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-12069606

RESUMO

Residues glutamate 156 (E156), aspartate 190 (D190), asparagine 181 (N181), lysine 186 (K186), and asparagine 191 (N191) in the active site of S-adenosylhomocysteine (AdoHcy) hydrolase have been mutated to alanine (A). AdoHcy hydrolase achieves catalysis of AdoHcy hydrolysis to adenosine (Ado) and homocysteine (Hcy) by means of a redox partial reaction (3'-oxidation of AdoHcy at the beginning and 3'-reduction of Ado at the end of the catalytic cycle) spanning an elimination/addition partial reaction (elimination of Hcy from the oxidized substrate and addition of water to generate the oxidized product), with the enzyme in an open NAD(+) form in the ligand-free state and in a closed NADH form during the elimination/addition partial reaction. Mutation K186A reduces the rate of a model enzymatic reaction for the redox partial reaction by a factor of 280000 and the rate of a model reaction for the elimination/addition partial reaction by a factor of 24000, consistent with a primary catalytic role in both partial reactions as a proton donor/acceptor at the 3'-OH/3'-keto center. Secondary roles for N181 and N191 in localizing the flexible side chain of K186 in a catalytically effective position are supported by rate reduction factors for N181A of 2500 (redox) and 240 (elimination/addition) and for N191A of 730 (redox) and 340 (elimination/addition). A role of D190 in orienting the substrate for effective transition-state stabilization is consistent with rate reduction factors of 1300 (redox) and 30 (elimination/addition) for D190A. Residue E156 may act to maintain K186 in the desired protonation state: rate deduction factors are 1100 (redox) and 70 (elimination/addition). The mutational increases in free energy barriers for k(cat)/K(M) are described by a linear combination of the effects for the partial reactions with the coefficients equal to the fractional degree that each partial reaction determines the rate for k(cat)/K(M). A similar linear equation for k(cat) overestimates the barrier increase by a uniform 5 kJ/mol, probably reflecting reactant-state stabilization by the wild-type enzyme that is abolished by the mutations.


Assuntos
Hidrolases/metabolismo , Adenosil-Homocisteinase , Sítios de Ligação/genética , Catálise , Humanos , Hidrolases/química , Hidrolases/genética , Modelos Químicos , Mutagênese Sítio-Dirigida , Oxirredução , Mutação Puntual , Estrutura Quaternária de Proteína/genética , Estrutura Secundária de Proteína/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Termodinâmica
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