Arrowhead Composite Microneedle Patches with Anisotropic Surface Adhesion for Preventing Intrauterine Adhesions

Abstract

Biomedical patches are considered as a promising strategy to help tissue repair and regeneration, prevent tissue adhesion, and reduce neighboring friction. Here, novel arrowhead composite microneedle patches (MNPs) are presented with anisotropic surface adhesion and growth factor encapsulation using a heterogeneous template replication approach for endometrium repair and intrauterine adhesions (IUAs) prevention. The arrowhead structures bring about interlocking between the microneedle (MN) tips and tissues, allowing these MNPs to steadily adhere to the tissues. Besides, benefitting from the cytoadhesive needle‐tip material and the antiadhesive base material, these MNPs possess anisotropic surface adhesion and can facilitate cell adhesion on one surface to repair damaged tissues while restrain tissue contact on the other to prevent adverse adhesion. In the meanwhile, the encapsulated growth factor can be delivered through the MNs to the deep tissue, further accelerating tissue repair. Additionally, as the bases are soft and their patterns are highly tunable, the MNPs can change their shapes flexibly to adjust to the irregular morphology of uteri. It is demonstrated that these MNPs show good performances in treating injured endometrium and preventing IUAs of a rat model, indicating their great potential in versatile postoperative adhesion prevention and other clinical applications.

Human Endometrium‐Derived Adventitial Cell Spheroid‐Loaded Antimicrobial Microneedles for Uterine Regeneration

“…In particular, when the GelMA concentration reached 30%, each needle of MN could withstand a compression force of more than 0.2 N, which was sufficient for the successful puncture of the endometrium. [32] After placing the MN patch to rat uterine tissue, the MN tips could penetrate and insert into the endometrium (Figure 2f and Figure S2b, Supporting Information). Moreover, histopathological damage was not observed in major organs after the MN patch was placed to rat uterus compared with the normal control, suggesting the safety of GelMA in vivo (Figure S3, Supporting Information).…”

Microneedles for in situ tissue regeneration

“… GelMA Arrays: Height: Shape: conical Strength: 0.3 ​N/needle CeO 2 nanozyme, stem cell antioxidant CeO 2 loaded base removed excessive ROS; Hydrogel needles improved stem cell activity, targeting efficiency and dwell time. [ 152 ] Arrowhead needles: GelMA; Base: bottom layer was N-acryloyl glycinamide (NAGA), top layer was PEGMA Arrays: Height: 760 ​μm Shape: Arrowhead Strength: 0.2 ​N/needle bFGF The arrowhead needles allowed MNs steadily adhering to the tissues and released growth factors; Backing layer prevented tissue adhesions [ 153 ] GelMA, Arrays: Height: 600 ​μm Shape: conical Strength: 0.2 ​N/needle Lactoferrin, human endometrium-derived adventitial cells Cells could rapidly form more biologically active three-dimensional cell spheres within the micropores surrounding the needles. Lactoferrin inhibited bacterial infections [ 154 ] …”

Dramatic improvement in the mechanical properties of polydopamine/polyacrylamide hydrogel mediated human amniotic membrane

“…The prevalence of intrauterine adhesions, a troublesome gynecological disease that poses a signicant risk to women's reproductive health, is one of the most pressing issues facing gynecologists today. [1][2][3][4][5] Human amniotic membrane (hAM) is an ideal material with great potential to prevent postoperative adhesion because of its natural biocompatibility and unique properties, such as self-contained stem cells, antibacterial properties, and exibility. Clinical studies have demonstrated that hAM can treat moderate and severe intrauterine adhesions with specic feasibility and safety benets, as the stem cells in hAM could effectively promote the repair of endometriosis.…”