US 11,925,731 B2
Sprayable stimuli-responsive micro-hydrogels for adhesion prevention and enhanced tissue healing
Timothy J. Keane, Jr., Houston, TX (US); Peter Alexander Smith, Houston, TX (US); and Stephen G. Ramon, Houston, TX (US)
Assigned to TEXAS MEDICAL CENTER, Houston, TX (US)
Filed by Texas Medical Center, Houston, TX (US)
Filed on Aug. 26, 2022, as Appl. No. 17/896,525.
Application 17/896,525 is a continuation of application No. PCT/US2021/020028, filed on Feb. 26, 2021.
Claims priority of provisional application 62/983,520, filed on Feb. 28, 2020.
Prior Publication US 2022/0401631 A1, Dec. 22, 2022
Int. Cl. A61L 31/14 (2006.01); A61L 31/00 (2006.01); A61L 31/04 (2006.01)
CPC A61L 31/145 (2013.01) [A61L 31/005 (2013.01); A61L 31/041 (2013.01); A61L 2400/06 (2013.01)] 17 Claims
 
1. A method for reducing postsurgical scarring at a target tissue, comprising:
(a) forming particles of a pre-gel mixture, the pre-gel mixture comprising an extracellular matrix (ECM) digest and a buffer solution, wherein the ECM digest comprises a collagen to carbohydrate ratio of at least about 70:1, wherein the buffer solution promotes a phase change of the pre-gel mixture to a hydro gel, wherein the particles of the pre-gel mixture have an average maximum dimension of at most 500 μm;
(b) applying the particles of the pre-gel mixture to the target tissue at a shear rate of at least 1 s−1; and
(c) promoting the formation of the hydrogel by 1) increasing a temperature of the pre-gel mixture by presenting the pre-gel mixture to the target tissue at a temperature that is lower than a temperature of the target tissue, 2) increasing a temperature of the pre-gel mixture by heating the pre-gel mixture, 3) exposing the pre-gel mixture to a light source; 4) interacting a chemical with the pre-gel mixture; 5) interacting an enzyme with the pre-gel mixture; or 6) a combination thereof, and
(d) forming a hydrogel film over the target tissue, wherein the hydrogel film is at least 10 μm thick, and comprises a storage modulus of at least 1,000 Pa when measured by parallel plate rheometry after gelation occurs isothermally at 37° C. at constant shear strain of 1% and a frequency of 1.6 Hz,
wherein the pre-gel mixture is applied onto the target tissue after completion of a surgical procedure,
wherein the forming of the hydrogel reduces the formation of adhesions on an adjacent tissue.