Highly Cross-Linked, Phosphorus-Based Hdrogels as Drug-Loaded Wound-Dressing

Dermal wounds are among the most predominant health care issues in the world, their treatment accounts for a great proportion of the health care budget in the United States and Europe. Wound care is crucial to reduce the chance of undesired infections and to help the body in the reconstruction of the compromised tissue.¹Current wound dressings lack adequate moisture balance and oxygen exchange which potentially leads to skin maceration, infections, and tissue damage by the constant changing of the material.¹ In fact, there are currently over 3000 types of commercial wound dressings, but none of them possess all the properties required to fully heal acute and/or chronic wounds.¹ Therefore, there is a great demand for novel wound-dressing materials that exhibit good skin compatibility, absorption, and local drug delivery, while retaining excellent mechanical properties.<br/>Hydrogels are interesting materials for application in biomedicine due to their outstanding properties, as they can absorb and release incredible amounts of water and drug molecules, and have superior biocompatibility, controllable physical properties, and abundant functional groups.² In other words, they are ideal candidates for drug delivery and/or moisture abstraction in wound-dressing applications. Recently, a class of synthetic, phosphodiester polymers has received considerable attention due to their great functionality.³ The phosphodiester bond constitutes one of the most relevant chemical bonds for humans. The introduction of phosphoesters into polymer backbones has therefore led to materials with outstanding biocompatibility and hydrolytic stability compared to polyesters, hemocompatible, or (bio)degradable materials.^4-5<br/>This work evaluates two series of phosphorus-based hydrogels as potential wound dressing candidates. The materials were synthesized <i>via</i> free-radical polymerization of bis[2-(methacryloyloxy)ethyl] phosphate (BMEP) (≥75 wt. %) with 3-Acrylamidopropyol)trimethylammonium chloride solution (APTAC) or 2-Acrylamido-2-methyl-1-propane sulfonic acid (AMPS). Due to optimized synthetic conditions, the materials displayed an unprecedented compressive elastic modulus (<i>E’</i>) reaching up to 0.19 MPa, which represents a 1000-fold increase compared to previously reported materials. Furthermore, the hydrogels displayed good hydrolytic stability, drug loading/release in wound-like pH conditions. Therefore, as these hydrogels possess both good, tunable mechanical properties and the ability to retain or release anionic or cationic drugs, this work demonstrates the potential of phosphorus-based hydrogels as drug-eluting wound-dressing materials.<br/>1. Borda, L. J.; Macquhae, F. E.; Kirsner, R. S. Wound Dressings: A Comprehensive Review. <i>Current Dermatology Reports</i>. Springer October 10, <b>2016</b>, pp 287–297. https://doi.org/10.1007/s13671-016-0162-5.<br/>2. Yang, Z.; Huang, R.; Zheng, B.; Guo, W.; Li, C.; He, W.; Wei, Y.; Du, Y.; Wang, H.; Wu, D.; Wang, H. Highly Stretchable, Adhesive, Biocompatible, and Antibacterial Hydrogel Dressings for Wound Healing. <i>Adv. Sci.</i> <b>2021</b>, <i>8</i> (8), 2003627. https://doi.org/10.1002/advs.202003627.<br/>3. Steinbach, T.; Wurm, F. R. Poly(Phosphoester)s: A New Platform for Degradable Polymers. <i>Angew. Chemie Int. Ed.</i> <b>2015</b>, <i>54</i> (21), 6098–6108. https://doi.org/10.1002/ANIE.201500147.<br/>4. Dera, R.; Diliën, H.; Billen, B.; Gagliardi, M.; Rahimi, N.; Van Den Akker, N. M. S.; Molin, D. G. M.; Grandfils, C.; Adriaensens, P.; Guedens, W.; Cleij, T. J. Phosphodiester Hydrogels for Cell Scaffolding and Drug Release Applications. <i>Macromol. Biosci.</i> <b>2019</b>, <i>19</i> (7). https://doi.org/10.1002/mabi.201900090.<br/>5. Dera, R.; Diliën, H.; Adriaensens, P.; Guedens, W.; Cleij, T. J. An Efficient Thermal Elimination Pathway toward phosphodiester Hydrogels via a Precursor Approach. <i>Macromol. Chem. Phys.</i> <b>2020</b>, <i>221</i> (5). https://doi.org/10.1002/macp.201900466.