Monitoring neovascularization and integration of decellularized human scaffolds using photoacoustic imaging

Abstract

Tissue engineering is a branch of regenerative medicine that aims to manipulate cells and scaffolds to create bioartificial tissues and organs for patients. A major challenge lies in monitoring the blood supply to the new tissue following transplantation: the integration and neovascularization of scaffolds in vivo is critical to their functionality. Photoacoustic imaging (PAI) is a laser-generated ultrasound-based technique that is particularly well suited to visualising microvasculature due to the high optical absorption of haemoglobin. Here, we describe an early proof-of-concept study in which PAI in widefield tomography mode is used to image biological, decellularized human tracheal scaffolds. We found that PAI allowed the longitudinal tracking of scaffold integration into subcutaneous murine tissue with high spatial resolution at depth over an extended period of time. The results of the study were consistent with post-imaging histological analyses, demonstrating that PAI can be used to non-invasively monitor the extent of vascularization in biological tissue-engineered scaffolds. We propose that this technique may be a valuable tool for studies designed to test interventions aimed at improving the speed and extent of scaffold neovascularization in tissue engineering. With technological refinement, it could also permit in vivo monitoring of revascularization in patients, for example to determine timing of heterotopic graft transfer.

An in vivo evaluation of induced chondrogenesis by decellularized extracellular matrix particles

“…Eight weeks post‐implantation, when an abundant dense tissue was formed, no cell infiltration was observed (Figure 2). According to similar observations, after subcutaneous implantation of decellularized cartilage, the cartilaginous portion of the scaffold did not cause serious cellular infiltration, probably as a result of its dense and avascular structure (Ogunlade et al, 2019). Here, we observed a large ectopic cartilage tissue portion after retrieval of DC‐ECM‐derived scaffolds at 8 weeks, which presumably prevents the infiltration of inflammatory cells.…”

Low-intensity pulsed ultrasound enhances angiogenesis in rabbit capsule tissue that acts as a novel vascular bed in vivo

“…27 The PAI technique is based on a combination of laser and ultrasound, which is particularly suitable for visualization of microvasculature due to high optical absorption of hemoglobin; it has proven valuable for monitoring neovascularization in tissue engineering. 28 The PAM is a new method for in vivo imaging of the microvasculature using high contrast and deep penetration, and has great potential for biomedical research. 29 Real-time in vivo monitoring of the vasculature enhances visualization of angiogenesis to provide an intuitive understanding of these processes for investigators.…”

Photoacoustic Imaging in Tissue Engineering and Regenerative Medicine

“…It is based on a hybrid technology that combines rich optical contrast mechanisms and superior ultrasonic penetration depth and resolution. [5][6][7][8][14][15][16] For PAI, photons from a nanosecond laser pulse are absorbed by certain endogenous chromophores or exogenous contrast agents in a tissue sample, causing impulsive heating and acoustic stress. The acoustic stress relaxes by launching broadband US pressure waves (i.e., PA emission), which propagate to the outside of the tissue and are detected by a mechanically scanned US receiver or an array of US receivers to form PA images.…”