Spatial regulation of controlled bioactive factor delivery for bone tissue engineering

Abstract

Limitations of current treatment options for critical size bone defects create a significant clinical need for tissue engineered bone strategies. This review describes how control over the spatiotemporal delivery of growth factors, nucleic acids, and drugs and small molecules may aid in recapitulating signals present in bone development and healing, regenerating interfaces of bone with other connective tissues, and enhancing vascularization of tissue engineered bone. State-of-the-art technologies used to create spatially controlled patterns of bioactive factors on the surfaces of materials, to build up 3D materials with patterns of signal presentation within their bulk, and to pattern bioactive factor delivery after scaffold fabrication are presented, highlighting their applications in bone tissue engineering. As these techniques improve in areas such as spatial resolution and speed of patterning, they will continue to grow in value as model systems for understanding cell responses to spatially regulated bioactive factor signal presentation in vitro, and as strategies to investigate the capacity of the defined spatial arrangement of these signals to drive bone regeneration in vivo.

Fluorescence light-up AIE probe for monitoring cellular alkaline phosphatase activity and detecting osteogenic differentiation

“…Detailed characterization data of the three probes using 1 H NMR, 13 C NMR, ESI-MS and HPLC are shown in Fig. S1-S3 (ESI †).…”

“…11 And specific differentiation factors (physical or chemical stimuli) are needed to accelerate the osteogenic differentiation and bone regeneration process. [12][13][14][15][16] During osteogenic differentiation, a series of enzymes, genes and proteins are up-regulated, which were identified as osteogenic markers to evaluate cell osteogenic differentiation. 17 Among them, alkaline phosphatase (ALP) has been identified as an important marker for osteogenic differentiation.…”

Molecular, Cellular and Pharmaceutical Aspects of Synthetic Hydroxyapatite Bone Substitutes for Oral and Maxillofacial Grafting

“…For discussion on antibiotic release from CaP materials see also the article of Prados-Frutos et al in this issue. Association of CaP ceramics with BMPs could be a way for a controlled release of these growth factors, which are intensively studied in many experimental and clinical fields of bone regeneration [114,119,121,122]. Further fields of application concern local delivery of anti-cancer drugs.…”

“…CaP ceramics did not play an outstanding role as scaffolds or carriers in bone tissue engineering research in the last decade [114]. However, experimental studies on the biofunctionalization of sHAs have already been performed and focus on the improvement of coatings to deliver biological agents and to develop smart materials [8].…”

Preclinical testing of drug delivery systems to bone

“…Growth factors used for bone regeneration are bone morphogenetic proteins (BMPs), Platelet Derived Growth Factor (PDGF), Vascular Endothelial Growth Factor (VEGF), Parathyroid hormone (PTH), and Insulin-like Growth Factor (IGF) [68]. BMP, PTH and IGF induce bone formation whereas PDGF and VEGF are important for vascularization.…”