Polyamidoamide Dendrimers and Cross-Linking Agents for Stabilized Bioenzymatic Resistant Metal-Free Bovine Collagen

Abstract

The work reports the use of polyamidoamine dendrimers (PAMAM) and a cross-linking agent, 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide/N-hydroxysuccinimide (EDC/NHS) or 4-(4,6-dimethoxy[1,3,5]triazin-2-yl)-4-methyl-morpholinium chloride (DMTMM), for the thermal stabilization of dermal bovine collagen. The efficiency of EDC/NHS/PAMAM and DMTMM/PAMAM in the cross-linking of collagen is correlated to the increase of the collagen shrinkage temperature (Ts), measured by differential scanning calorimetry (DSC). An alternative enzymatic protocol was adopted to measure the degradability of EDC/NHS/PAMAM tanned hides; these data are correlated to the thermal stability values measured by DSC. In the presence of PAMAMs, EDC/NHS provides very high stabilization of bovine dermal collagen, giving Ts of up to 95 °C, while DMTMM achieves lower stabilization. Preliminary tanning tests carried out in best reaction conditions show that EDC/NHS/PAMAM could be an interesting, environmentally-sustainable tanning system which is completely free of metals, formaldehyde, and phenols. Two new unreported dendrimeric species were synthesized and employed.

Sustainable Triazine-Based Dehydro-Condensation Agents for Amide Synthesis

“…In this frame, dehydro-condensation reactions are a well-known and consolidated protocol for the synthesis of amides, although toxic dehydro-condensation agents are often used to promote the reaction [ 17 , 19 ]. For example, carbodiimides such as dicyclohexylcarbodiimide (DCC) or 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide chlorohydrate (EDC) employed in combination with N -hydroxysuccinimide (NHS), have frequently been employed for the scope ( Figure 1 ) [ 20 , 21 , 22 , 23 ].…”

“…In this prospective, quaternary ammonium salts of 2-halo-4,6-dialkoxy-1,3,5-triazines, e.g., 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM(Cl)), (see Figure 2 ), represent a valid alternative for the formation of amide bonds both in organic and water solvent [ 20 , 21 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. In the last years, DMTMM(Cl), commonly known as DMTMM, has found many applications as dehydro-condensation agent for the synthesis of amides and esters [ 36 , 40 ], collagen cross-linking [ 7 , 21 , 38 ], preparation of carboxymethylcellulose based films [ 39 ], amine grafting on hyaluronan [ 20 , 40 , 41 ], and peptide synthesis [ 42 ]. Additionally, the synthesis of a library of 2-(4,6-dimethoxy-1,3,5-triazinyl)trialkyl ammonium salts (DMT-Ams(X), X: Cl − or ClO 4 − ) and their activity as dehydro-condensation agents for the synthesis of amides, has been reported by Kunishima et al [ 43 ] ( Figure 2 ).…”

Fabrication of Dexamethasone-Silver Nanoparticles Entrapped Dendrimer Collagen Matrix Nanoparticles for Dental Applications

“…Glutaraldehyde is toxic, whereas EDC is a zero-length crosslinker i.e., it can be successfully removed either by dialysis or centrifugation from the system. Reports have also suggested that cross-linking PAMAM with collagen is a better way for safe biomedical applications [63,64]. As the dental matrix is predominately made up of collagen Type I [65], we activated the carboxylic group amino acids present in collagen and was allowed to form a covalent amide bond with the amine group of the dendrimer.…”

Efficient Triazine Derivatives for Collagenous Materials Stabilization

“…Triazine tanning agents are gaining increasing interest in recent years as valid, environmentally friendly alternatives that are metal-, formaldehyde-, and phenol-free [ 15 , 29 , 30 , 31 , 32 ]. Presently the leather industry is suffering from restrictions due to the ECHA-REACH regulation, which has significantly limited the variety of chemical substances allowed as tanning agents.…”

“…Our research group has long been involved in the study of innovative, sustainable processes for the industry and leather processing [ 29 , 35 , 36 ]. In the last years, 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methyl-morpholinium chloride (DMTMM) has found many applications as dehydro-condensation agent for collagen cross-linking [ 29 , 30 , 37 ], amine grafting on hyaluronan [ 38 ], amide, and peptide synthesis [ 39 , 40 , 41 , 42 , 43 ]. DMTMM is a very efficient cross-linking agent which promotes the reaction between carboxylic and amine groups in mild reaction conditions to form amides.…”