Photocurable injectable Janus hydrogel with minimally invasive delivery for all-in-one treatment of gastric perforations and postoperative adhesions

Background: Surgical sutures for sealing gastric perforations (GP) are associated with severe inflammation and postoperative adhesions. Hydrogel bioadhesives offer a potential alternative for sutureless repair of GP; however, their application in minimally invasive surgery is limited due to their prefabricated patch-form, lacking in situ gelation capability. In this study, we emphasized an all-in-one minimally invasive strategy for sutureless repair of acute GP. Methods: an injectable photocurable Janus hydrogel was synthesized, and their ability to seal GP was performed. A rat GP model was used to verify the wound healing and antiadhesion efficiency of hydrogels, and a rabbit GP model was used to verify their laparoscopic feasibility. A fresh human corpse GP model was further employed to verify the user-friendliness of a minimally invasive deliverable (MID) device. A minipig GP model was utilized to evaluate the all-in-one minimally invasive strategy for the treatment of acute GP. Results: Such injectable Janus hydrogel exhibited asymmetric adhesiveness, where the inner-facing side of the hydrogel displays strong sealing and wound healing abilities for GP, while the outward-facing side prevents postoperative adhesion formation. We further developed a minimally invasive deliverable (MID) device integrating hydrogel-delivery parts and photocrosslinking-gelation parts in a laparoscope system. The precise delivery and rapid fluid-tight sealing process of the injectable Janus hydrogel using the MID device for in situ GP repair were demonstrated in a simulated clinical scenario. The in vivo effectiveness of GP sutureless repair was successfully validated in porcine models, with further exploration of the underlying mechanism. Conclusions: Our findings reveal that the injectable Janus hydrogel offers an all-in-one strategy for sutureless GP repair and concurrent prevention of postoperative adhesion formation by incorporating the MID device in minimally invasive surgery, presenting the significant potential to reduce patient surgical complications.

 If the wet-adhesiveness is less than 5kPa, the score of hydrogels was -1, otherwise it is 1;  If the hydrogel is not asymmetrically adhesive, the score of hydrogels was -1, otherwise it is 1;  If the in vivo degradation time is between 7~14 days (the peak of postoperative adhesions), the score of hydrogels was 1, otherwise it is 1;  If the gelation of hydrogels needs oxidation agent, the score of hydrogels was -1, otherwise it is 1;  If the hydrogel is injectable, the feasibility of laparoscopy scored 1, otherwise it is -1;  If the time of gelation is over 30s, the score of hydrogels was -1, otherwise it is 1;  Y: Maneuverability of laparoscopic surgery=the sum score of "oxidation agent", the feasibility of laparoscopy" and "time of gelation".
Table S2.The standard scoring system was used to evaluate the degree of adhesion.

Score Peritoneal adhesion No adhesion One thin filmy adhesion More than one thin adhesion Thick adhesion with the focal point Thick adhesion with plantar attachment or more than one thick adhesion with focal point
Very thick vascularized adhesion or more than one plantar adhesion Table S3.Sequences of primers used in RT-qPCR

Primer
Figure S1.(A) Schematics on the synthesis of the HAD formulation.(B) 1 HNMR spectra of HAD

Figure S2 .
Figure S2.(A) HAD hydrogel was able to adhere to both outside and the inside wall of the porcine

Figure
Figure S3.(A) HAD hydrogels robustly adhered to the ex vivo porcine perforation under the torsion

Figure
Figure S4.(A) Schematic diagram of the bursting press test.(B) Practical diagram of the bursting

Figure
Figure S5.(A) HAD hydrogels still robustly adhered to the ex vivo porcine perforation when imposed

Figure S6 .
Figure S6.Procedures of establishing an artificial defect on the rat stomach, which was treated by

Figure S7 .
Figure S7.Macroscopic photo of rat gastric wounds in each group 7 days after surgery.Adhesion tissues

Figure S9 .
Figure S9.Fluorescence images of ICG stained HAD hydrogels on 1, 7, and 14 days after the

Figure
Figure S10.(A) Representative H&E staining of tissue sections in different groups after abdominal

Figure S13 .
Figure S13.Gross observation of rabbits treated by the laparoscopy on day 14.Obvious trocar induced

Figure S14 .
Figure S14.The practical operations of sealing gastric defects via the MID (minimally invasive

Figure S15 .
Figure S15.The relationship between fiber length and UV intensity.Specifically, the UV light

Figure S16 .Figure S17 .
Figure S16.The preoperative preparations of applying the minimally invasive integrated device (MID)

Figure S18 .
Figure S18.(A)The preparations for the minipig acute gastric models.Anesthesia was maintained with

Figure S19 .
Figure S19.Schematic illustration (A) and laparoscopic imaging (B) of acute perforation models with

Figure S20 .
Figure S20.Laparoscopic images of gastric perforations in the HAD (A) and Model group (B) on day

Figure S21 .
Figure S21.The porcine gastric tissues were harvested for further histopathological examination on day

Figure S22 .
Figure S22.(A) Immunofluorescence staining of CD206 (red) and CD68 (green) in HAD group on day

Figure S23 .
Figure S23.(A) Immunofluorescence staining of CD31 (red) and PCNA (green) in the model group

Figure S25 .
Figure S25.(A) Immunofluorescence staining of CD206 (red) and CD68 (green) in HAD group on day

Figure S26 .
Figure S26.(A) Immunofluorescence staining of CD31 (red) and PCNA (green) in the model group

Table S1 .
Comprehensive properties of recent hydrogel-based anti-adhesion barriers.