In situ gelation properties of a collagen–genipin sol with a potential for the treatment of gastrointestinal ulcers

Abstract

We investigated the potential of collagen–genipin sols as biomaterials for treating artificial ulcers following endoscopic submucosal dissection. Collagen sol viscosity increased with condensation, allowing retention on tilted ulcers before gelation and resulting in collagen gel deposition on whole ulcers. The 1.44% collagen sols containing genipin as a crosslinker retained sol fluidity at 23°C for >20 min, facilitating endoscopic use. Collagen sols formed gel depositions on artificial ulcers in response to body temperature, and high temperature responsiveness of gelation because of increased neutral phosphate buffer concentration allowed for thick gel deposition on tilted ulcers. Finally, histological observations showed infiltration of gels into submucosal layers. Taken together, the present data show that genipin-induced crosslinking significantly improves the mechanical properties of collagen gels even at low genipin concentrations of 0.2–1 mM, warranting the use of in situ gelling collagen–genipin sols for endoscopic treatments of gastrointestinal ulcers.

Collagen-Based Materials Modified by Phenolic Acids—A Review

“…It may suggest that naturally derived compounds proposed as cross-linkers are more appropriate for materials dedicated to biomedical applications. cross-linkers may be added to collagen, including aldehydes (e.g., glutaraldehyde, formaldehyde, glyoxal) [60][61][62][63][64][65][66][67][68][69], genipin [70][71][72][73][74][75][76][77][78][79][80][81], polyphenols (e.g., phenolic acids) [81], a mixture of EDC/NHS [82][83][84], and starch dialdehyde [85][86][87][88][89][90][91]; they can also be cross-linked by mixing with other polymers, both natural (e.g., chitosan, hyaluronic acid) [92][93][94] and synthetic (e.g., polyurethane, polyvinyl alcohol) [95].…”

“…Collagen may be modified by physical methods, e.g., by exposure to UV irradiation, enzyme acting [ 44 , 45 , 46 , 47 ], or by dehydrothermal treatment and photooxidation [ 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ]. Additionally, chemical cross-linkers may be added to collagen, including aldehydes (e.g., glutaraldehyde, formaldehyde, glyoxal) [ 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ], genipin [ 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 ], polyphenols (e.g., phenolic acids) [ 81 ], a mixture of EDC/NHS [ 82 , 83 , 84 ], and starch dialdehyde [ 85 , 86 , 87 , 88 , 89 , 90 , 91 ]; they can also be cross-linked ...…”

A novel method for continuous formation of cord‐like collagen gels to fabricate durable fibers in which collagen fibrils are longitudinally aligned

“…In this study, t max was decreased by the use of 2× NPB and warming at 38°C [Figure (a)] to cause the optimal rate of fibril formation during shearing, whereas 2.25× NPB and a warming temperature of 37°C were used in the previous rotary shearing experiments . A high concentration of NPB may cause gradual fibril formation even at an ambient temperature . This should be considered for continuous CCG formation using a syringe as a reservoir of neutral collagen sols.…”

“…A 1% collagen solution in dilute HCl (pH 3) was concentrated to 3.0% in a rotary evaporator at 29°C without denaturing the collagen . Aliquots (25 g) of condensed collagen solution were stored in 50‐mL biological tubes at 4°C.…”

Recent Advances in the Development of In Situ Gelling Drug Delivery Systems for Non-Parenteral Administration Routes

“…Narita et al investigated the capability of collagen–genipin solutions for endoscopic treatments of gastrointestinal ulcers [ 84 ]. Genipin acted as cross-linker.…”