skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Explore Research Products in the PAR
It may take a few hours for recently added research products to appear in PAR search results.


Title: Microphysiological systems for the modelling of wound healing and evaluation of pro-healing therapies
Wound healing is a multivariate process involving the coordinated response of numerous proteins and cell types. Accordingly, biomedical research has seen an increased adoption of the use of in vitro wound healing assays with complexity beyond that offered by traditional well-plate constructs. These microphysiological systems (MPS) seek to recapitulate one or more physiological features of the in vivo microenvironment, while retaining the analytical capacity of more reductionist assays. Design efforts to achieve relevant wound healing physiology include the use of dynamic perfusion over static culture, the incorporation of multiple cell types, the arrangement of cells in three dimensions, the addition of biomechanically and biochemically relevant hydrogels, and combinations thereof. This review provides a brief overview of the wound healing process and in vivo assays, and we critically review the current state of MPS and supporting technologies for modelling and studying wound healing. We distinguish between MPS that seek to inform a particular phase of wound healing, and constructs that have the potential to inform multiple phases of wound healing. This distinction is a product of whether analysis of a particular process is prioritized, or a particular physiology is prioritized, during design. Material selection is emphasized throughout, and relevant fabrication techniques discussed.  more » « less
Award ID(s):
1847488 1846911
PAR ID:
10176842
Author(s) / Creator(s):
; ;
Date Published:
Journal Name:
Journal of Materials Chemistry B
ISSN:
2050-750X
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; ; ; ; ; ; ; (, Advanced Healthcare Materials)
    Abstract Butyrate is a key bacterial metabolite that plays an important and complex role in modulation of immunity and maintenance of epithelial barriers. Its translation to clinic is limited by poor bioavailability, pungent smell, and the need for high doses, and effective delivery strategies have yet to realize clinical potential. Here, a novel polymeric delivery platform for tunable and sustainable release of butyrate consisting of a methacrylamide backbone with butyryl ester or phenyl ester side chains as well as mannosyl side chains, which is also applicable to other therapeutically relevant metabolites is reported. This platform's utility in the treatment of non‐healing diabetic wounds is explored. This butyrate‐containing material modulated immune cell activation in vitro and induced striking changes in the milieu of soluble cytokine and chemokine signals present within the diabetic wound microenvironment in vivo. This novel therapy shows efficacy in the treatment of non‐healing wounds through the modulation of the soluble signals present within the wound, and importantly accommodates the critical temporal regulation associated with the wound healing process. Currently, the few therapies to address non‐healing wounds demonstrate limited efficacy. This novel platform is positioned to address this large unmet clinical need and improve the closure of otherwise non‐healing wounds. 
    more » « less
  2. ; ; ; (, bioRxiv)
    Abstract Immune response is critical in septic wound healing. The aberrant and imbalanced signaling dynamics primarily cause a dysfunctional innate immune response, exacerbating pathogen invasion of injured tissue and further stalling the healing process. To design biological controllers that regulate the critical divergence of the immune response during septicemia, we need to understand the intricate differences in immune cell dynamics and coordinated molecular signals of healthy and sepsis injury. Here, we deployed an ordinary differential equation (ODE)-based model to capture the hyper and hypo-inflammatory phases of sepsis wound healing. Our results indicate that impaired macrophage polarization leads to a high abundance of monocytes, M1, and M2 macrophage phenotypes, resulting in immune paralysis. Using a model-based analysis framework, we designed a biological controller which successfully regulates macrophage dysregulation observed in septic wounds. Our model describes a systems biology approach to predict and explore critical parameters as potential therapeutic targets capable of transitioning septic wound inflammation toward a healthy, wound-healing state. 
    more » « less
  3. ; ; ; (, Northeast Bioengineering Conference)
    Previous work demonstrated an accelerated in vitro and in vivo wound healing response when insulinoma cells were used to deliver insulin to scratches in keratinocyte mono- layers and chronic diabetic excise wounds in mice, respectively. When combined with mesenchymal stem cells (MSCs), the response was amplified (healing in 14 vs. 35+ days). To isolate the role of insulin in the response and exclude any potential contribution of an unknown cancer moiety released by the insulinoma cells, the effect on wound healing of multiple lines derived from the same insulinoma was examined. 
    more » « less
  4. ; ; ; (, Northeast Bioengineering Conference)
    Previous work demonstrated an accelerated in vitro and in vivo wound healing response when insulinoma cells were used to deliver insulin to scratches in keratinocyte mono- layers and chronic diabetic excise wounds in mice, respectively. When combined with mesenchymal stem cells (MSCs), the response was amplified (healing in 14 vs. 35+ days). To isolate the role of insulin in the response and exclude any potential contribution of an un known cancer moiety released by the insulinoma cells, the effect on wound healing of multiple lines derived from the same insulinoma was examined. 
    more » « less
  5. ; ; ; ; ; ; ; ; ; (, Journal of Materials Chemistry B)
    Zwitterionic hydrogels, as highly hydrated and soft materials, have been considered as promising materials for wound dressing, due to their unique antifouling and mechanical properties. While the viscoelasticity and softness of zwitterionic hydrogels are hypothetically essential for creating adaptive cellular niches, the underlying mechanically regulated wound healing mechanism still remains elusive. To test this hypothesis, we fabricated zwitterionic poly(sulfobetaine methacrylate) (polySBMA) hydrogels with different elastic moduli prepared at different crosslinker contents, and then applied the hydrogels to full-thickness cutaneous wounds in mice. In vivo wound healing studies compared the mechanical cue-induced effects of soft and stiff polySBMA hydrogels on wound closure rates, granulation tissue formation and collagen deposition. Collective results showed that the softer and more viscoelastic hydrogels facilitated cell proliferation, granulation formation, collagen aggregation, and chondrogenic ECM deposition. Such high wound healing efficiency by the softer hydrogels is likely attributed to stress dissipation by expanding the cell proliferation, the up-regulation of blood vessel formation, and the enhanced polarization of M2/M1 macrophages, both of which would provide more oxygen and nutrients for cell proliferation and migration, leading to enhanced wound repair. This work not only reveals a mechanical property–wound healing relationship of zwitterionic polySBMA hydrogels, but also provides a promising candidate and strategy for the next-generation of wound dressings. 
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Save / Share this Record
  • Send to Email