Dermal wounds are a major global health burden made worse by common comorbidities such as diabetes and infection. Appropriate wound closure relies on a highly coordinated series of cellular events, ultimately bridging tissue gaps and regenerating normal physiological structures. Wound dressings are an important component of wound care management, providing a barrier against external insults while preserving the active reparative processes underway within the wound bed. The development of wound dressings with biomaterial constituents has become an attractive design strategy due to the varied functions intrinsic in biological polymers, such as cell instructiveness, growth factor binding, antimicrobial properties, and tissue integration. Using photosensitive agents to generate crosslinked or photopolymerized dressings in situ provides an opportunity to develop dressings rapidly within the wound bed, facilitating robust adhesion to the wound bed for greater barrier protection and adaptation to irregular wound shapes. Despite the popularity of this fabrication approach, relatively few experimental wound dressings have undergone preclinical translation into animal models, limiting the overall integrity of assessing their potential as effective wound dressings. Here, we provide an up‐to‐date narrative review of reported photoinitiator‐ and wavelength‐guided design strategies for in situ light activation of biomaterial dressings that have been evaluated in preclinical wound healing models.
- NSF-PAR ID:
- 10391533
- Date Published:
- Journal Name:
- Soft Science
- Volume:
- 2
- Issue:
- 2
- ISSN:
- 2769-5441
- Page Range / eLocation ID:
- 9
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract -
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
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Abstract Chronic wounds are one of the most devastating complications of diabetes and are the leading cause of nontraumatic limb amputation. Despite the progress in identifying factors and promising in vitro results for the treatment of chronic wounds, their clinical translation is limited. Given the range of disruptive processes necessary for wound healing, different pharmacological agents are needed at different stages of tissue regeneration. This requires the development of wearable devices that can deliver agents to critical layers of the wound bed in a minimally invasive fashion. Here, for the first time, a programmable platform is engineered that is capable of actively delivering a variety of drugs with independent temporal profiles through miniaturized needles into deeper layers of the wound bed. The delivery of vascular endothelial growth factor (VEGF) through the miniaturized needle arrays demonstrates that, in addition to the selection of suitable therapeutics, the delivery method and their spatial distribution within the wound bed is equally important. Administration of VEGF to chronic dermal wounds of diabetic mice using the programmable platform shows a significant increase in wound closure, re‐epithelialization, angiogenesis, and hair growth when compared to standard topical delivery of therapeutics.
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Impaired wound healing is a significant financial and medical burden. The synthesis and deposition of extracellular matrix (ECM) in a new wound is a dynamic process that is constantly changing and adapting to the biochemical and biomechanical signaling from the extracellular microenvironments of the wound. This drives either a regenerative or fibrotic and scar-forming healing outcome. Disruptions in ECM deposition, structure, and composition lead to impaired healing in diseased states, such as in diabetes. Valid measures of the principal determinants of successful ECM deposition and wound healing include lack of bacterial contamination, good tissue perfusion, and reduced mechanical injury and strain. These measures are used by wound-care providers to intervene upon the healing wound to steer healing toward a more functional phenotype with improved structural integrity and healing outcomes and to prevent adverse wound developments. In this review, we discuss bioengineering advances in 1) non-invasive detection of biologic and physiologic factors of the healing wound, 2) visualizing and modeling the ECM, and 3) computational tools that efficiently evaluate the complex data acquired from the wounds based on basic science, preclinical, translational and clinical studies, that would allow us to prognosticate healing outcomes and intervene effectively. We focus on bioelectronics and biologic interfaces of the sensors and actuators for real time biosensing and actuation of the tissues. We also discuss high-resolution, advanced imaging techniques, which go beyond traditional confocal and fluorescence microscopy to visualize microscopic details of the composition of the wound matrix, linearity of collagen, and live tracking of components within the wound microenvironment. Computational modeling of the wound matrix, including partial differential equation datasets as well as machine learning models that can serve as powerful tools for physicians to guide their decision-making process are discussed.more » « less
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Abstract Wound debridement is crucial for proper wound care as it promotes fast and efficient wound healing through removal of necrotic tissue. The latter not only impairs new healthy tissue formation but also increases the odour and the wound exudate, allowing bacteria and other harmful foreign invaders to spread and infect the wound. Hydrogel wound dressings are usually applied for promoting autolytic wound debridement but this is slow and not a very efficient process. On the other hand, enzymatic products for wound debridement are either ointments or gels and they are easily washed out when used for treating highly exuding wounds. This study is an attempt to combine enzymatic debridement functionality with the high swelling ability of polyzwitterionic networks and to produce an innovative dressing with debridement functionality for the healing of highly exuding wounds. For this purpose, two polyzwitterionic hydrogels were synthesized, poly(sulfobetaine methacrylate) and poly(carboxybetaine methacrylate) hydrogels, which were loaded with the protease subtilisin DY for imparting debridement functionality. The swelling ability and mechanical properties of zwitterionic polymer (ZP) hydrogels were shown to depend on their different propensities to physical network formation. Poly(carboxybetaine methacrylate) hydrogels demonstrated better capacity for wound exudate absorption as well as for exerting higher enzymatic debridement activity. Both ZP hydrogels were shown to be non‐cytotoxic which confirms their appropriateness for direct contact with injured tissues. Thus, the newly developed ZP hydrogels demonstrate the potential to be used as new dressing materials with enzymatic debridement functionality for highly exuding wounds. © 2019 The Authors.
Polymer International published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.20517/ss.2022.13
