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.
A fundamental mechanism of tissue regeneration from biodegradable synthetic acellular vascular grafts is the effective interplay between graft degradation, erosion and the production of extracellular matrix. In order to understand this crucial process of graft erosion and degradation, we conducted an investigation of grafts ( = 4 at days 1, 4, 7, 10 each) exposed to enzymatic degradation. Herein, we provide constitutive relationships for mass loss and mechanical properties based on much-needed experimental data. Furthermore, we formulate a mathematical model to provide a physics-based framework for understanding graft erosion. A novel finding is that despite their porous nature, grafts lost mass exponentially via surface erosion demonstrating a 20% reduction in outer diameter and no significant change in apparent density. A diffusion based, concentration gradient-driven mechanistic model of mass loss through surface erosion was introduced which can be extended to an setting through the use of two degradation parameters. Furthermore, notably, mechanical properties of degrading grafts did not scale with mass loss. Thus, we introduced a damage function scaling a neo-Hookean model to describe mechanical properties of the degrading graft; a refinement to existing mass-dependent growth and remodelling (G&R) models. This framework can be used to improve accuracy of well-established G&R theories in biomechanics; tools that predict evolving structure-function relationships of neotissues and guide graft design.
Background The purpose of this study is to assess the feasibility of a novel microporous annealed particle (MAP) scaffolding hydrogel to enable both articular cartilage and subchondral bone biointegration and chondrocyte regeneration in a rat knee osteochondral defect model. Methods An injectable, microporous scaffold was engineered and modified to match the mechanical properties of articular cartilage. Two experimental groups were utilized—negative saline control and MAP gel treatment group. Saline and MAP gel were injected into osteochondral defects created in the knees of Sprague-Dawley rats. Photo-annealing of the MAP gel was performed. Qualitative histologic and immunohistochemical analysis was performed of the treated defects at 2, 4, and 8 weeks postsurgery. Results The injectable MAP gel successfully annealed and was sustained within the osteochondral defect at each timepoint. Treatment with MAP gel resulted in maintained size of the osteochondral defect with evidence of tissue ingrowth and increased glycosaminoglycan production, whereas the control defects presented with evidence of disorganized scar tissue. Additionally, there was no significant inflammatory response to the MAP gel noted on histology. Conclusions We have demonstrated the successful delivery of an injectable, flowable MAP gel scaffold into a rat knee osteochondral defect with subsequent annealing and stable integration into the healing wound. The flowable nature of this scaffold allows for minimally invasive application, for example, via an arthroscopic approach for management of wrist arthritis. The MAP gel was noted to fill the osteochondral defect and maintain the defect dimensions and provide a continuous and smooth surface for cartilage regeneration, suggesting its ability to provide a stable scaffold for tissue ingrowth. Future chemical, mechanical, and biological gel modifications may improve objective evidence of cartilage regeneration.
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.
The microporous annealed particle (MAP) scaffold platform is a subclass of granular hydrogels. It is composed of an injectable slurry of microgels that can form a structurally stable scaffold with cell-scale porosity in situ following a secondary lightbased chemical crosslinking step (i.e., annealing). MAP scaffold has shown success in a variety of regenerative medicine applications, including dermal wound healing, vocal fold augmentation, and stem cell delivery. This paper describes the methods for synthesis and characterization of poly(ethylene glycol) (PEG) microgels as the building blocks to form a MAP scaffold. These methods include the synthesis of a custom annealing macromer (MethMAL), determination of microgel precursor gelation kinetics, microfluidic device fabrication, microfluidic generation of microgels, microgel purification, and basic scaffold characterization, including microgel sizing and scaffold annealing. Specifically, the high-throughput microfluidic methods described herein can produce large volumes of microgels that can be used to generate MAP scaffolds for any desired application, especially in the field of regenerative medicine.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.