Drug delivery for bone tissue engineering mediated by three-dimensional biomimetic scaffolds
Creators: name: Faber, Jessica
Publisher: name: University of Iowa
Year: 2024
Subjects: Bone Tissue Regeneration
Drug Delivery
public abstract

description: Critical-sized bone defects remain an unmet clinical challenge due to the shortcomings of current treatments. Autologous bone grafts are considered the gold standard treatment for bone regeneration of critical-sized defects; yet they are associated with many complications and limitations related to bone harvesting, such as donor site morbidity, high cost, and limited availability. Biomaterial-based tissue engineering strategies offer a promising alternative to autologous bone grafts. However, a challenge arises when attempting to effectively deliver bioactive factors(drugs)/cells from three-dimensional (3D) tissue engineering scaffolds. To address this challenge, I have developed two kinds of biomimetic scaffolds based on natural and synthetic polymers with distinct drug delivery techniques. 3D printing is emerging as a promising scaffold fabrication tool due to its low cost, high degree of customization, and standardization. However, conventional 3D printing is unable to fabricate nanosized structures and also has severely limited bioactive factors/cells delivery capabilities. My first strategy utilizes nanomaterials to functionalize 3D printed polycaprolactone (PCL) scaffolds by incorporating localized drug delivery and a nanofibrous structure. While PCL is an FDA approved synthetic polymer for bone repair, its hydrophobic and bioinert nature necessitate modifications. Polydopamine (PDA), a natural mussel inspired polymer, can coat the pre-modified (neat) PCL scaffolds to increase collagen binding. Collagen provides the nanofibrous structure present in bone’s extra cellular matrix (ECM) that enhances cell attachment. Finally, nanoclay is incorporated into the collagen gel for prolonged and sustained drug delivery. Nanoclay is a nanomaterial with drug binding capabilities due to its unique 2D structure and charged surfaces. By combining these materials to create a drug delivery system and an osteoconductive environment, I developed a scaffold primed for bone regeneration.
description: Gelatin, a natural polymer formed from denatured collagen, serves as the basis for fabricating 3D gelatin nanofibrous scaffolds (GF). This scaffold possesses a unique nanofibrous and interconnected macroporous structure created through the thermally induced phase separation and porogen leaching (TIPS+P) method. Although its collagen-mimicking nanofibrous structure is appealing for osteogenesis, its limited drug-binding capacity impedes its success in bone regeneration. Heparin, a naturally occurring glycosaminoglycan, can facilitate sustained release of growth factors mainly through its strong negative charge. However, heparin’s capacity to facilitate drug release by functionalizing GF scaffolds is less studied. I hypothesized heparin will be able to control drug release from the GFH scaffold and subsequently increase bone regeneration. Therefore, the GF scaffold is further modified through chemically crosslinking it with heparin (GFH). To investigate the potential of the GFH scaffold, I tested the effects of heparin-conjugation on the physical structure and bioactivity of the scaffold in addition to the binding and release of bone morphogenetic protein 2 (BMP2).
description: Similar methods were used to investigate both scaffolds’ structure, drug delivery abilities, and osteogenic potential. Scanning electron, fluorescent and confocal microscopy imaged the morphology of the scaffolds as well as their interaction with pre-osteoblast MC3T3-E1 cells. The in vitro results with MC3T3-E1 cells supported the ability of the scaffolds to increase the activity of osteogenic differentiation marker alkaline phosphatase (ALP) and improve matrix mineralization. The findings presented in this study provide strong evidence that nanoclay and heparin enabled drug binding/sustained release are effective and versatile techniques for distinct 3D scaffolds with promising potential for tissue engineering applications.