Heparin Microislands in Microporous Annealed Particle Scaffolds for Accelerated Diabetic Wound Healing (Adv. Funct. Mater. 35/2021)

Abstract

In article number 2104337, Donald Griffin and co-workers present heterogeneously distributed heparin microislands within a microporous annealed particle hydrogel as a new type of bioactive scaffold that can promote extensive cell migration and enhanced healing without the addition of exogenous growth factors. This innovative materials-only approach has high translational potential for biomedical applications requiring accelerated tissue integration.

An Optimally Designed Engineering Exosome–Reductive COF Integrated Nanoagent for Synergistically Enhanced Diabetic Fester Wound Healing

“…It is well known that diabetic wounds are characterized by their difficulty to turn inflammatory phase into proliferation phase in wound healing. [ 52 ] The PCOF@E‐Exo formulation takes advantage of antioxidant and anti‐inflammatory roles in terms of injuring stimulus ceases, realizing initiation of the proliferative stage of the healing cascade. As expected, we observed that untreated or monotherapy diabetic mice fester wounds were hard to heal even at day 21, while wounds on mice who received PCOF@E‐Exo formulation looked healed by gross examination.…”

Delivery of Dissociated Islets Cells within Microporous Annealed Particle Scaffold to Treat Type 1 Diabetes

“…For animal studies, a minority of microgels containing immobilized thiolated heparin were included heterogeneously throughout the MAP scaffold to promote accelerated vascularization. [ 27 ] All microgels were synthesized using a high‐throughput microfluidics technique as previously described. [ 31 ] After separate microgel synthesis and purification, heparin‐containing microgels were mixed in with the no‐heparin microgels at a 1:10 ratio (10% heparin‐μislands).…”

“…We chose to investigate the delivery of dissociated islets (as a model cell type for stem‐cell derived beta cells) without pre‐implantation conditioning using microporous annealed particle (MAP) scaffold, which is an injectable biomaterial composed entirely of hydrogel microspheres that are annealed in situ to provide a material environment with cell‐scale porosity. [ 23 ] The MAP scaffold platform has been previously used to accelerate dermal wound healing, [ 23 ] but has since been shown to be successful in a multitude of other regenerative medicine applications, [ 24,25 ] including serving as a delivery vehicle for stem cells, [ 26 ] conveying anti‐inflammatory effects to host tissues through recruitment of pro‐regenerative macrophages, [ 27 ] and promoting a Th2 “tissue repair” type T‐cell response. [ 28 ] For this study, we chose to use a recently designed MAP scaffold formulation comprised of a heterogenous composition that adds heparin‐containing microspheres (heparin μislands), which has previously demonstrated the ability to organize endogenous growth factors in a diabetic wound environment and significantly improve re‐vascularization.…”

“…[ 28 ] For this study, we chose to use a recently designed MAP scaffold formulation comprised of a heterogenous composition that adds heparin‐containing microspheres (heparin μislands), which has previously demonstrated the ability to organize endogenous growth factors in a diabetic wound environment and significantly improve re‐vascularization. [ 27,29 ] Given our success using MAP scaffold as an angiogenic and immunomodulatory biomaterial capable of cell delivery, we were motivated to use MAP as a delivery platform for dissociated islet cells (containing beta, alpha, and delta cells) to treat T1D in mice. By mixing dissociated islet cells with MAP and assembling the scaffold in situ ( Figure A), we were able to support cell organization, survival, and function for a prolonged period, which did not require prior in vitro formation of pseudoislets.…”

“…The MAP scaffold contains heparin‐μislands, which has previously demonstrated to significantly improve vascularization within the scaffold. [ 27 ] B) 3D rendering of MAP scaffold pores (green dextran) and heparin‐μisland particles (red) in Imaris software (Oxford Instruments). Imaris software was also used to quantify the surface area of the pores, which was then converted to circular pore diameters.…”