Seeing Through the Surface: Non-invasive Characterization of Biomaterial-Tissue Interactions Using Photoacoustic Microscopy

At the intersection of life sciences, materials science, engineering, and medicine, regenerative medicine stands out as a rapidly progressing field that aims at retaining, restoring, or augmenting tissue/organ functions to promote the human welfare. While the field has witnessed tremendous advancements over the past few decades, it still faces many challenges. For example, it has been difficult to visualize, monitor, and assess the functions of the engineered tissue/organ constructs, particularly when three-dimensional scaffolds are involved. Conventional approaches based on histology are invasive and therefore only convey end-point assays. The development of volumetric imaging techniques such as confocal and ultrasonic imaging has enabled direct observation of intact constructs without the need of sectioning. However, the capability of these techniques is often limited in terms of penetration depth and contrast. In comparison, the recently developed photoacoustic microscopy (PAM) has allowed us to address these issues by integrating optical and ultrasonic imaging to greatly reduce the effect of tissue scattering of photons with one-way ultrasound detection while retaining the high optical absorption contrast. PAM has been successfully applied to a number of studies, such as observation of cell distribution, monitoring of vascularization, and interrogation of biomaterial degradation. In this review article, we highlight recent progress in non-invasive and volumetric characterization of biomaterial–tissue interactions using PAM. We also discuss challenges ahead and envision future directions

On the Thermodynamics and Experimental Control of Twinning in Metal Nanocrystals

International audienceThis work demonstrates a new strategy for controlling the evolution of twin defects in metal nanocrystals by simply following thermodynamic principles. With Ag nanocrystals supported on amorphous SiO2 as a typical example, we establish that twin defects can be rationally generated by equilibrating nanoparticles of different sizes through heating and then cooling. We validate that Ag nanocrystals with icosahedral, decahedral, and single‐crystal structures are favored at sizes below 7 nm, between 7 and 11 nm, and greater than 11 nm, respectively. This trend is then rationalized by computational studies based on density functional theory and molecular dynamics, which show that the excess free energy for the three equilibrium structures correlate strongly with particle size. This work not only highlights the importance of thermodynamic control but also adds another synthetic method to the ever‐expanding toolbox used for generating metal nanocrystals with desired properties.

Fabrication of cell patches using biodegradable scaffolds with a hexagonal array of interconnected pores (SHAIPs)

Cell patches are widely used for healing injuries on the surfaces or interfaces of tissues such as those of epidermis and myocardium. Here we report a novel type of porous scaffolds made of poly(d,l-lactic-co-glycolic acid) for fabricating cell patches. The scaffolds have a single layer of spherical pores arranged in a unique hexagonal pattern and are therefore referred to as “scaffolds with a hexagonal array of interconnected pores (SHAIPs)”. SHAIPs contain both uniform pores and interconnecting windows that can facilitate the exchange of biomacromolecules, ensure homogeneous cell seeding, and promote cell migration. As a proof-of-concept demonstration, we have created skeletal muscle patches with a thickness of approximately 150 μm using SHAIPs. The myoblasts seeded in the scaffolds maintained high viability and were able to differentiate into multi-nucleated myotubes. Moreover, neovasculature could efficiently develop into the patches upon subcutaneous implantation in vivo

Melanocortin 1 receptor targeted imaging of melanoma with gold nanocages and positron emission tomography

Purpose: Melanoma is a lethal skin cancer with unmet clinical needs for targeted imaging and therapy. Nanoscale materials conjugated with targeting components have shown great potential to improve tumor delivery efficiency while minimizing undesirable side effects in vivo. Herein, we proposed to develop targeted nanoparticles for melanoma theranostics. Method: In this work, gold nanocages (AuNCs) were conjugated with α-melanocyte-stimulating hormone (α-MSH) peptide and radiolabeled with 64Cu for melanocortin 1 receptor-(MC1R) targeted positron emission tomography (PET) in a mouse B16/F10 melanoma model. Results: Their controlled synthesis and surface chemistry enabled well-defined structure and radiolabeling efficiency. In vivo pharmacokinetic evaluation demonstrated comparable organ distribution between the targeted and nontargeted AuNCs. However, micro-PET/computed tomography (CT) imaging demonstrated specific and improved tumor accumulation via MC1R-mediated delivery. By increasing the coverage density of α-MSH peptide on AuNCs, the tumor delivery efficiency was improved. Conclusion: The controlled synthesis, sensitive PET imaging, and optimal tumor targeting suggested the potential of targeted AuNCs for melanoma theranostics. </jats:sec

Gold nanocages as contrast agents for photoacoustic imaging

Gold nanoparticles with tunable absorption and scattering properties have been developed as contrast agents for various optical imaging techniques. As a hybrid modality that combines the merits of both optical and ultrasonic imaging, photoacoustic (PA) imaging also benefits from the use of these nanoparticles to greatly enhance the contrast for visualization of structures and biomarkers in biological tissues. Gold nanocages characterized by hollow interiors, ultrathin and porous walls are of particular interest for in vivo PA imaging because of their compact sizes, bio‐inertness and well‐defined surface chemistry, as well as their strong and highly wavelength‐tunable optical absorption in the near‐infrared (NIR) optical window of soft tissues. This review discusses the application of gold nanocages as a new class of contrast agents for PA imaging in the context of cancer diagnosis

Electrospun Nanofibers for Neural Tissue Engineering

Biodegradable nanofibers produced by electrospinning represent a new class of promising scaffolds to support nerve regeneration. We begin with a brief discussion on electrospinning of nanofibers and methods for controlling the structure, porosity, and alignment of the electrospun nanofibers. The methods include control of the nanoscale morphology and microscale alignment for the nanofibers, as well as the fabrication of macroscale, three-dimensional tubular structures. We then highlight recent studies that utilize electrospun nanofibers to manipulate biological processes relevant to nervous tissue regeneration, including stem cell differentiation, guidance of neurite extension, and peripheral nerve injury treatments. The main objective of this feature article is to provide valuable insights into methods for investigating the mechanisms of neurite growth on novel nanofibrous scaffolds and optimization of the nanofiber scaffolds and conduits for repairing peripheral nerve injuries

The effect of adipose-derived stem cell sheets and CTGF on early flexor tendon healing in a canine model

Oral History interview of Curt Sawyer. Interview conducted by Robin Dunn

Label-free photoacoustic microscopy of cytochrome c in cells

Cytochrome c is a heme protein normally bound to mitochondria and is important for mitochondrial electron transport and apoptosis initiation. Since cytochrome c is nonfluorescent, it is always labeled with fluorescent molecules for imaging, which, however, may affect normal cellular functions. Here, label-free photoacoustic microscopy (PAM) of mitochondrial cytochrome c was realized for the first time by utilizing the optical absorption around the Soret peak. PAM was demonstrated to be sensitive enough to image mitochondrial cytochrome c at 422 nm wavelength. Mitochondrial cytochrome c in the cytoplasm of fixed fibroblasts was clearly imaged by PAM as confirmed by fluorescent labeling. By showing mitochondrial cytochrome c in various cells, we demonstrated the feasibility of PAM for label-free histology of mouse ear sections. Therefore, PAM can sensitively image cytochrome c in unstained cells at 422 nm wavelength and has great potential for functional imaging of cytochrome c in live cells or in vivo

Nanofiber Scaffolds with Gradations in Mineral Content for Mimicking the Tendon-to-Bone Insertion Site

We have demonstrated a simple and versatile method for generating a continuously graded, bonelike calcium phosphate coating on a nonwoven mat of electrospun nanofibers. A linear gradient in calcium phosphate content could be achieved across the surface of the nanofiber mat. The gradient had functional consequences with regard to stiffness and biological activity. Specifically, the gradient in mineral content resulted in a gradient in the stiffness of the scaffold and further influenced the activity of mouse preosteoblast MC3T3 cells. This new class of nanofiberbased scaffolds can potentially be employed for repairing the tendon-to-bone insertion site via a tissue engineering approach