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Nanolayered siRNA delivery platforms for local silencing of CTGF reduce cutaneous scar contraction in third-degree burns.

ABSTRACT: Wound healing is an incredibly complex biological process that often results in thickened collagen-enriched healed tissue called scar. Cutaneous scars lack many functional structures of the skin such as hair follicles, sweat glands, and papillae. The absence of these structures contributes to a number of the long-term morbidities of wound healing, including loss of function for tissues, increased risk of re-injury, and aesthetic complications. Scar formation is a pervasive factor in our daily lives; however, in the case of serious traumatic injury, scars can create long-lasting complications due to contraction and poor tissue remodeling. Within this report we target the expression of connective tissue growth factor (CTGF), a key mediator of TGF? pro-fibrotic response in cutaneous wound healing, with controlled local delivery of RNA interference. Through this work we describe both a thorough in vitro analysis of nanolayer coated sutures for the controlled delivery of siRNA and its application to improve scar outcomes in a third-degree burn induced scar model in rats. We demonstrate that the knockdown of CTGF significantly altered the local expression of ?SMA, TIMP1, and Col1a1, which are known to play roles in scar formation. The knockdown of CTGF within the healing burn wounds resulted in improved tissue remodeling, reduced scar contraction, and the regeneration of papillary structures within the healing tissue. This work adds support to a number of previous reports that indicate CTGF as a potential therapeutic target for fibrosis. Additionally, we believe that the controlled local delivery of siRNA from ultrathin polymer coatings described within this work is a promising approach in RNA interference that could be applied in developing improved cancer therapies, regenerative medicine, and fundamental scientific research.

SUBMITTER: Castleberry SA

PROVIDER: S-EPMC5518795 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Nanolayered siRNA delivery platforms for local silencing of CTGF reduce cutaneous scar contraction in third-degree burns.

Castleberry Steven A SA Golberg Alexander A Sharkh Malak Abu MA Khan Saiqa S Almquist Benjamin D BD Austen William G WG Yarmush Martin L ML Hammond Paula T PT

Biomaterials 20160414

Wound healing is an incredibly complex biological process that often results in thickened collagen-enriched healed tissue called scar. Cutaneous scars lack many functional structures of the skin such as hair follicles, sweat glands, and papillae. The absence of these structures contributes to a number of the long-term morbidities of wound healing, including loss of function for tissues, increased risk of re-injury, and aesthetic complications. Scar formation is a pervasive factor in our daily li ...[more]

PMID: 27108403

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Project description:BackgroundScar assessment plays a key role during burns aftercare, to monitor scar remodelling and patients' psychosocial well-being. To aid assessment, subjective scar assessment scales are available that use health-care professionals' and patients' opinions to score scar characteristics. The subjective scales are more widely used in clinical practice over objective scar measures. To date, there is no research that considers patients' views on scar assessment and the role of subjective and objective assessment tools. Therefore, the aim of this qualitative study was to explore patients' perspectives on scar assessment and the utility of scar assessment tools during burns rehabilitation.MethodsSemi-structured interviews were conducted with 10 adult burn patients who were being reviewed in clinic for scarring. Participants were recruited via their clinical care team and research nurses at the Queen Elizabeth Hospital, Birmingham, UK. Topics covered during interview included patient experience of scar assessment, the use of scar assessment tools and discussion surrounding important factors to be addressed when assessing scars. A thematic analysis using the Framework Method was conducted.ResultsParticipants identified key subthemes that contribute towards the overarching theme of patient-centred scar assessment. These are: patient-led care; continuity in care; learning how to self-manage scarring; and psychological assessment. Links were demonstrated between these subthemes and the remaining themes that describe scar assessment strategies, indicating their potential patient-centred contributions. The subjective opinions of clinicians were found to be valued above the use of subjective or objective scar assessment tools. Scar assessment scales were perceived to be a beneficial method for self-reflection in relation to psychosocial functioning. However, minimal feedback and review of completed assessment scales led to uncertainty regarding their purpose. Patients perceived objective tools to be of primary use for health-care professionals, though the measures may aid patients' understanding of scar properties.ConclusionsScar assessment tools should be used to support, rather than replace, health-care professionals' subjective judgements of scarring. Adapting the way in which clinicians introduce and use scar assessment tools, according to patient needs, can support a patient-centred approach to scar assessment.

Dataset Information

Nanolayered siRNA delivery platforms for local silencing of CTGF reduce cutaneous scar contraction in third-degree burns.

Publications

Nanolayered siRNA delivery platforms for local silencing of CTGF reduce cutaneous scar contraction in third-degree burns.

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