Mimicking growth factor-extracellular matrix interactions for promoting cell migration is a powerful technique to improve tissue integration with biomaterial scaffolds for the regeneration of damaged tissues. This is attempted by scaffold-mediated controlled delivery of exogenous growth factors; however, the predetermined nature of this delivery can limit the scaffold's ability to meet each wound's unique spatiotemporal regenerative needs and presents translational hurdles. To address this limitation, a new approach to growth factor organization is presented that incorporates heparin microislands (μIslands), which are spatially isolated heparin-containing microparticles that can reorganize and protect endogenous local growth factors via heterogeneous sequestration at the microscale in vitro and result in functional improvements in wound healing. More specifically, the heparin μIslands are incorporated within microporous annealed particle scaffolds, which allows facile tuning of microenvironment heterogeneity through ratiometric mixing of microparticle sub-populations. In this manuscript, the ability of heparin μIslands to heterogeneously sequester applied growth factor and control downstream cell migration in vitro is demonstrated. Further, their ability to significantly improve wound healing outcomes (epidermal regeneration and re-vascularization) in a diabetic wound model relative to two clinically relevant controls is presented.

Objectives/Hypothesis The purpose of this study was to develop and provide evidence of a novel permanent injectable biomaterial for vocal fold augmentation with the potential to treat glottic incompetence by evaluating its performance in two animal models. Study Design Animal model. Methods Microporous annealed particle (MAP) hydrogel was fabricated using a water‐in‐oil emulsion method and synthetically tuned to match the stiffness modulus of native vocalis muscle. Thirty‐two New Zealand White rabbits were administered unilateral injections of MAP (n = 16), saline (n = 8), and the clinical standard hyaluronic acid (Restylane‐L) (n = 8), and evaluated at day 0, and 6‐week, 4‐month, and 6‐month endpoints. Induced vocal fold vibration was recorded with a high‐speed camera prior to euthanization, with glottic closure and mucosal wave characteristics assessed both quantitatively and qualitatively by an experienced voice clinician. Histologic analysis was performed to assess scaffold permanence, immunogenicity, and vascularization within the scaffold. Results Histologic analysis confirmed the MAP gel treatment group maintained its volume without migration for 6 months postimplantation. Immune staining showed minimal to nonexistent immunogenicity over the course of the implant lifetime. Extensive tissue integration and vascularization was observed histologically within the MAP gel group by immunofluorescence staining. Mucosal wave was not impaired by any of the injected materials, including the MAP gel augmentation. Conclusions MAP gel is a nonresorbable biostimulatory injectable implant that provides superior tissue integration, stiffness matching, and permanence compared to current injectable implants, with retained biomechanical function, suggesting its potential as a new therapeutic for glottic incompetence. Level of Evidence NA Laryngoscope, 130:2432–2441, 2020

We present lyophilized heparin microgels which can be directly rehydrated with epidermal growth factor and mixed with PEG microgels to form heterogenous MAP scaffolds. These EGF-releasing MAP scaffolds promote accelerated dermal wound healing.

Microporous annealed particle (MAP) scaffolds consist of a slurry of hydrogel microspheres that undergo annealing to form a solid scaffold. MAP scaffolds have contained functional groups with dual abilities to participate in Michael-type addition (gelation) and radical polymerization (photoannealing). Functional groups with efficient Michael-type additions react with thiols and amines under physiological conditions, limiting usage for therapeutic delivery. We present a heterofunctional maleimide/ methacrylamide 4-arm PEG macromer (MethMal) engineered for selective photopolymerization compatible with multiple polymer backbones. Rheology using two classes of photoinitiators demonstrates advantageous photopolymerization capabilities. Functional assays show benefits for therapeutic delivery and 3D printing without impacting cell viability.

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.