TY - JOUR
T1 - Injectable polyisocyanide hydrogel as healing supplement for connective tissue regeneration in an abdominal wound model
AU - Gudde, Aksel N.
AU - van Velthoven, Melissa J. J.
AU - Kouwer, Paul H. J.
AU - Roovers, Jan-Paul W. R.
AU - Guler, Zeliha
N1 - Funding Information: This work was supported by ZonMw (grant number – 91218030 ). Publisher Copyright: © 2023 The Author(s)
PY - 2023/11/1
Y1 - 2023/11/1
N2 - In pelvic organ prolapse (POP) patients, the uterus, bladder and/or rectum descends into vagina due to weakened support tissues. High recurrence rates after POP surgery suggest an urgent need for improved surgical outcomes. Our aim is to promote connective tissue healing that results in stimulated tissue support functions by surgically applying a hydrogel functionalized with biological cues. We used known vaginal wound healing promoting factors (basic fibroblast growth factor, β-estradiol, adipose-derived stem cells) in the biomimetic and injectable polyisocyanide (PIC) hydrogel, which in itself induces regenerative vaginal fibroblast behavior. The regenerative capacity of injected PIC hydrogel, and the additional pro-regenerative effects of these bioactive factors was evaluated in abdominal wounds in rabbits. Assessment of connective tissue healing (tensile testing, histology, immunohistochemistry) revealed that injection with all PIC formulations resulted in a statistically significant stiffness and collagen increase over time, in contrast to sham. Histological evaluation indicated new tissue growth with moderate to mild immune activity at the hydrogel – tissue interface. The results suggest that PIC injection in an abdominal wound improves healing towards regaining load-bearing capacity, which encourages us to investigate application of the hydrogel in a more translational vaginal model for POP surgery in sheep.
AB - In pelvic organ prolapse (POP) patients, the uterus, bladder and/or rectum descends into vagina due to weakened support tissues. High recurrence rates after POP surgery suggest an urgent need for improved surgical outcomes. Our aim is to promote connective tissue healing that results in stimulated tissue support functions by surgically applying a hydrogel functionalized with biological cues. We used known vaginal wound healing promoting factors (basic fibroblast growth factor, β-estradiol, adipose-derived stem cells) in the biomimetic and injectable polyisocyanide (PIC) hydrogel, which in itself induces regenerative vaginal fibroblast behavior. The regenerative capacity of injected PIC hydrogel, and the additional pro-regenerative effects of these bioactive factors was evaluated in abdominal wounds in rabbits. Assessment of connective tissue healing (tensile testing, histology, immunohistochemistry) revealed that injection with all PIC formulations resulted in a statistically significant stiffness and collagen increase over time, in contrast to sham. Histological evaluation indicated new tissue growth with moderate to mild immune activity at the hydrogel – tissue interface. The results suggest that PIC injection in an abdominal wound improves healing towards regaining load-bearing capacity, which encourages us to investigate application of the hydrogel in a more translational vaginal model for POP surgery in sheep.
KW - Bioactive factors
KW - Immune response
KW - Pelvic organ prolapse
KW - Polyisocyanide hydrogel
KW - Regeneration
UR - http://www.scopus.com/inward/record.url?scp=85173170527&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.biomaterials.2023.122337
DO - https://doi.org/10.1016/j.biomaterials.2023.122337
M3 - Article
C2 - 37793268
SN - 0142-9612
VL - 302
JO - Biomaterials
JF - Biomaterials
M1 - 122337
ER -