|Author:||Bei, Ho Pan|
|Title:||Functionalized electrospun scaffold as dressing for skin and bone repair|
|Advisors:||Zhao, Xin (BME)|
Hong Kong Polytechnic University -- Dissertations
|Department:||Department of Biomedical Engineering|
|Pages:||74 pages : color illustrations|
|Abstract:||Electrospinning is an advanced technique for creation of nanofibrous structures. Its versatility and flexibility to create varied nanofibers and scaffolds enabled fabrication of biomimetic structures. Of note, many of the human organs and tissues exhibit nanofibrous architecture owing to the nature of extracellular matrix, which consists of fibrils of nanoscale that encourage cell adhesion. Thus, many studies have been inspired by this happy coincidence and fully utilized electrospinning for creating artificial tissues such as skin, periosteum and neural sheaths. The use of nanofibers for tissue engineering have proved to become extremely beneficial both bench side and clinical owing to its unique capabilities to support cell growth and provide a platform for localized release of therapeutics. However, existing techniques leave much to be desired: The inherently low drug diffusion distance causes fast leakage of encapsulated therapeutics; The use of natural polymers in electrospinning favours cell adhesion and biocompatibility, but lacks long-term stability or drug release owing to the hydrolysis of polymer chains. Additionally, their lack of intrinsic strength causes them to rupture easily under external stress, which limits their sites of application. Here we introduce two novel studies to improve on existing electrospinning technology for the creation of artificial skin for prevention of hypertrophic scar, and the synthesis of reinforced natural polymer artificial periosteum for bone regeneration. Hypertrophic scarring has no definitive known cause, but afflicts millions of patients worldwide. Current understanding of scar pathophysiology mainly attributes it to the occurrence of inflammation and disruptions in intrinsic signaling of fibroblasts which cause them to overproliferate and form fibrous tissues. To address the clinical issue, invasive techniques such as injection of inhibitory drugs and surgical excision have been employed with limited success. Notably, the lack of sustained supply of fibroblast inhibitors lead to high recurrence rate of scar formation. Here, we employed a core-sheath electrospun fibrous scaffold encapsulating polymer brush grafted mesoporous silica nanoparticles for delivery of anti-scarring agents. The scaffold demonstrates sustained release of small molecules over 90 days, and successfully inhibited the proliferation of fibroblasts without significantly impeding cell adhesion. Rabbit ear hypertrophic scar model also well demonstrated the clinical relevancy of the anti-scarring fibrous scaffold through reduction in scar thickness and reduced collagen deposition in low dosage groups, indicating the success of this long-term drug delivery strategy. The periosteum is a dense, fibrous structure covering the surface of bones and rich with architectures that recruit osteoblasts and endothelial cells. Studies have proven that the periosteum exhibits strong osteogenesis and angiogenesis during bone regeneration, and that the damaged tissues lead to slow recovery or incomplete healing. Studies in the past have fabricated fibrous artificial periosteum with osteogenic-angiogenic coupling, but their mechanical properties are lacking and cannot resemble the toughness of native periosteum. Here we employed a natural polymer/artificial polymer network alongside organic/inorganic crosslinking network with acrylate group functionalized hydroxyapatite nanoparticles and ionic interactions with L-arginine for the fabrication of a robust, nanofibrous periosteum with high bioactivity and release of therapeutics to stimulate the NO/cGMP pathway for the simultaneous promotion of osteogenesis and angiogenesis. The addition of various components into the system greatly enhanced GelMA's inherent low strength, and imbued it with osteogenic and angiogenic properties. The scaffold exhibited good biocompatibility for both MSCs and HUVECs, and was able to induce bone formation and vessel formation in each cell types respectively.|
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