Targeted and Sustained Delivery of a Focal Adhesion Kinase Inhibitor via Pullulan-Collagen Hydrogel Scaffolds for Scarless Wound Healing in a Mouse Excisional Wound Model
Kun (Cathy) Ma, M.D., Ph.D.1, Dominik Duscher, M.D.1, Yixiao Dong, Ph.D.1, Mohammed Inayathullah, Ph.D.2, Jayakumar Rajadas, Ph.D.2, Geoffrey Gurtner, M.D.1.
1Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University, Stanford, CA, USA, 2BioADD Laboratory, Stanford University, Stanford, CA, USA.
PURPOSE: Skin fibrosis and contractures resulting from traumatic soft tissue injury can cause significant disfigurement and dysfunction to the injured patients. Unfortunately, current anti-scarring therapies have proven inadequate in treating these conditions. Previous investigation has demonstrated that focal adhesion kinase (FAK) plays a critical mechanosensory role in hypertrophic scarring and offers a promising target for therapy. This study aims to provide a novel approach to scar reduction by performing sustained and targeted delivery of FAK-inhibitor (FAK-I) from pullulan-collagen hydrogel scaffolds.
METHODS: A novel Molecular Imprinting technique was used to encapsulate FAK-I into pullulan-collagen hydrogel. Effects of imprinted hydrogel on wound healing and scar formation were further investigated in a mouse excisional wound model.
RESULTS: Subcutaneous implantation of a small molecule imprinted pullulan-collagen hydrogel to the mouse groin resulted in up to 21 days of sustained release, in contrast to 3 hours of fast release in the non-imprinted hydrogel/molecule mixture group (Fig. 1). Furthermore, compared with the control group, wounds in FAK-I imprinted hydrogel group (H+FAK-I) closed 3 days earlier (Fig. 2) with significantly reduced expression of fibrosis marker proteins (collagen and α-SMA) (Fig. 3 and Fig. 4) and enhanced mechanical properties.
CONCLUSIONS: It highlights a great potential of developing a novel and effective anti-scarring approach by targeted and sustained delivery of anti-fibrosis drug(s) through manipulation of biomaterial-based drug delivery capabilities.
Fig. 4: Immunofluorescence staining.
Fig. 3: Masson’s Trichrome Staining.
Fig. 1: Detection of small molecules released from molecule-imprinted hydrogel (arrows) and a non-imprinted group (arrow head).
Fig. 2: Wound images.
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