Assessment of tissue response in vivo: PET-CT imaging of titanium and biodegradable magnesium implants.

To study in vivo the bioactivity of biodegradable magnesium implants and other possible biomaterials, we are proposing a previously unexplored application of PET-CT imaging, using available tracers to follow soft tissue and bone remodelling and immune response in the presence of orthopaedic implants. Female Wistar rats received either implants (Ti6Al7Nb titanium or WE43 magnesium) or corresponding transcortical sham defects into the diaphyseal area of the femurs. Inflammatory response was followed with [18F]FDG and osteogenesis with [18F]NaF, over the period of 1.5 months after surgery. An additional pilot study with [68Ga]NODAGA-RGD tracer specific to αvß3 integrin expression was performed to follow the angiogenesis for one month. [18F]FDG tracer uptake peaked on day 3 before declining in all groups, with Mg and Ti groups exhibiting overall higher uptake compared to sham. This suggests increased cellular activity and tissue response in the presence of Mg during the initial weeks, with Ti showing a subsequent increase in tracer uptake on day 45, indicating a foreign body reaction. [18F]NaF uptake demonstrated the superior osteogenic potential of Mg compared to Ti, with peak uptake on day 7 for all groups. [68Ga]NODAGA-RGD pilot study revealed differences in tracer uptake trends between groups, particularly the prolonged expression of αvß3 integrin in the presence of implants. Based on the observed differences in the uptake trends of radiotracers depending on implant material, we suggest that PET-CT is a suitable modality for long-term in vivo assessment of orthopaedic biomaterial biocompatibility and underlying tissue reactions. STATEMENT OF SIGNIFICANCE: The study explores the novel use of positron emission tomography for the assessment of the influence that biomaterials have on the surrounding tissues. Previous related studies have mostly focused on material-related effects such as implant-associated infections or to follow the osseointegration in prosthetics, but the use of PET to evaluate the materials has not been reported before. The approach tests the feasibility of using repeated PET-CT imaging to follow the tissue response over time, potentially improving the methodology for adopting new biomaterials for clinical use.

MRI Application and Challenges of Hyperpolarized Carbon-13 Pyruvate in Translational and Clinical Cardiovascular Studies: A Literature Review.

Cardiovascular disease shows, or may even be caused by, changes in metabolism. Hyperpolarized magnetic resonance spectroscopy and imaging is a technique that could assess the role of different aspects of metabolism in heart disease, allowing real-time metabolic flux assessment in vivo. In this review, we introduce the main hyperpolarization techniques. Then, we summarize the use of dedicated radiofrequency 13C coils, and report a state of the art of 13C data acquisition. Finally, this review provides an overview of the pre-clinical and clinical studies on cardiac metabolism in the healthy and diseased heart. We furthermore show what advances have been made to translate this technique into the clinic in the near future and what technical challenges still remain, such as exploring other metabolic substrates.

Biosustainable Hybrid Nanoplatforms as Photoacoustic Agents.

The development of biosafe theranostic nanoplatforms has attracted great attention due to their multifunctional behavior, reduced potential toxicity, and improved long-term safety. When considering photoacoustic contrast agents and photothermal conversion tools, melanin and constructs like melanin are highly appealing due to their ability to absorb optical energy and convert it into heat. Following a sustainable approach, in this study, silver-melanin like-silica nanoplatforms are synthesized exploiting different bio-available and inexpensive phenolic acids as potential melanogenic precursors and exploring their role in tuning the final systems architecture. The UV-Vis combined with X-Ray Diffraction investigation proves metallic silver formation, while Transmission Electron Microscopy analysis reveals that different morphologies can be obtained by properly selecting the phenolic precursors. By looking at the characterization results, a tentative formation mechanism is proposed to explain how phenolic precursors' redox behavior may affect the nanoplatforms' structure. The antibacterial activity experiments showed that all synthesized systems have a strong inhibitory effect on Escherichia coli, even at low concentrations. Furthermore, very sensitive Photoacoustic Imaging capabilities and significant photothermal behavior under laser irradiation are exhibited. Finally, a marked influence of phenol nature on the final system architecture is revealed resulting in a significant effect on both biological and photoacoustic features of the obtained systems. These melanin-based hybrid systems exhibit excellent potential as triggerable nanoplatforms for various biomedical applications.

Early investigation of a novel SI306 theranostic prodrug for glioblastoma treatment.

Glioblastoma multiforme (GBM) is one of the most aggressive malignancies with a high recurrence rate and poor prognosis. Theranostic, combining therapeutic and diagnostic approaches, arises as a successful strategy to improve patient outcomes through personalized medicine. Src is a non-receptor tyrosine kinase (nRTK) whose involvement in GBM has been extensively demonstrated. Our previous research highlighted the effectiveness of the pyrazolo[3,4-d]pyrimidine SI306 and its more soluble prodrug CMP1 as Src inhibitors both in in vitro and in vivo GBM models. In this scenario, we decided to develop a theranostic prodrug of SI306, ProSI-DOTA(68 Ga) 1, which was designed to target GBM cells after hydrolysis and follow-up on the disease's progression and improve the therapy's outcome. First, the corresponding nonradioactive prodrug 2 was tested to evaluate its ADME profile and biological activity. It showed good metabolic stability, no inhibition of CYP3A4, suboptimal aqueous solubility, and slight gastrointestinal and blood-brain barrier passive permeability. Compound 2 exhibited a drastic reduction of cell vitality after 72 h on two different GBM cell lines (GL261 and U87MG). Then, 2 was subjected to complexation with the radionuclide Gallium-68 to give ProSI-DOTA(68 Ga) 1. The cellular uptake of 1 was evaluated on GBM cells, highlighting a slight but significant time-dependent uptake. The data obtained from our preliminary studies reflect the physiochemical properties of 1. The use of an alternative route of administration, such as the intranasal route, could overcome the physiochemical limitations and enhance the pharmacokinetic properties of 1, paving the way for its future development.

Targeting the Translocator Protein (18 kDa) in Cardiac Diseases: State of the Art and Future Opportunities.

Mitochondria dysfunctions are typical hallmarks of cardiac disorders (CDs). The multiple tasks of this energy-producing organelle are well documented, but its pathophysiologic involvement in several manifestations of heart diseases, such as altered electromechanical coupling, excitability, and arrhythmias, is still under investigation. The human 18 kDa translocator protein (TSPO) is a protein located on the outer mitochondrial membrane whose expression is altered in different pathological conditions, including CDs, making it an attractive therapeutic and diagnostic target. Currently, only a few TSPO ligands are employed in CDs and cardiac imaging. In this Perspective, we report an overview of the emerging role of TSPO at the heart level, focusing on the recent literature concerning the development of TSPO ligands used for fighting and imaging heart-related disease conditions. Accordingly, targeting TSPO might represent a successful strategy to achieve novel therapeutic and diagnostic strategies to unravel the fundamental mechanisms and to provide solutions to still unanswered questions in CDs.

Hybrid Nanoparticle-Assisted Chemo-Photothermal Therapy and Photoacoustic Imaging in a Three-Dimensional Breast Cancer Cell Model.

Bioinspired nanoparticles have recently been gaining attention as promising multifunctional nanoplatforms for therapeutic applications in cancer, including breast cancer. Here, the efficiency of the chemo-photothermal and photoacoustic properties of hybrid albumin-modified nanoparticles (HSA-NPs) loaded with doxorubicin was evaluated in a three-dimensional breast cancer cell model. The HSA-NPs showed a higher uptake and deeper penetration into breast cancer spheroids than healthy breast cell 3D cultures. Confocal microscopy revealed that, in tumour spheroids incubated with doxorubicin-loaded NPs for 16 h, doxorubicin was mainly localised in the cytoplasm, while a strong signal was detectable at the nuclear level after 24 h, suggesting a time-dependent uptake. To evaluate the cytotoxicity of doxorubicin-loaded NPs, tumour spheroids were treated for up to 96 h with increasing concentrations of NPs, showing marked toxicity only at the highest concentration of doxorubicin. When doxorubicin administration was combined with laser photothermal irradiation, enhanced cytotoxicity was observed at lower concentrations and incubation times. Finally, the photoacoustic properties of doxorubicin-loaded NPs were evaluated in tumour spheroids, showing a detectable signal increasing with NP concentration. Overall, our data show that the combined effect of chemo-photothermal therapy results in a shorter exposure time to doxorubicin and a lower drug dose. Furthermore, owing to the photoacoustic properties of the NPs, this nanoplatform may represent a good candidate for theranostic applications.

Enhanced Photoacoustic Response by Synergistic Ag-Melanin Interplay at the Core of Ternary Biocompatible Hybrid Silica-Based Nanoparticles.

Photoacoustics (PA) is gaining increasing credit among biomolecular imaging methodologies by virtue of its poor invasiveness, deep penetration, high spatial resolution, and excellent endogenous contrast, without the use of any ionizing radiation. Recently, we disclosed the excellent PA response of a self-structured biocompatible nanoprobe, consisting of ternary hybrid nanoparticles with a silver core and a melanin component embedded into a silica matrix. Although preliminary evidence suggested a crucial role of the Ag sonophore and the melanin-containing nanoenvironment, whether and in what manner the PA response is controlled and affected by the self-structured hybrid nanosystems remained unclear. Because of their potential as multifunctional platforms for biomedical applications, a detailed investigation of the metal-polymer-matrix interplay underlying the PA response was undertaken to understand the physical and chemical factors determining the enhanced response and to optimize the architecture, composition, and performance of the nanoparticles for efficient imaging applications. Herein, we provide the evidence for a strong synergistic interaction between eumelanin and Ag which suggests an important role in the in situ-generated metal-organic interface. In particular, we show that a strict ratio between melanin and silver precursors and an accurate choice of metal nanoparticle dimension and the kind of metal are essential for achieving strong enhancements of the PA response. Systematic variation of the metal/melanin component is thus shown to offer the means of tuning the stability and intensity of the photoacoustic response for various biomedical and theranostic applications.

A simple and robust nanosystem for photoacoustic imaging of bladder cancer based on α5ß1-targeted gold nanorods.

BACKGROUND: Early detection and removal of bladder cancer in patients is crucial to prevent tumor recurrence and progression. Because current imaging techniques may fail to detect small lesions of in situ carcinomas, patients with bladder cancer often relapse after initial diagnosis, thereby requiring frequent follow-up and treatments. RESULTS: In an attempt to obtain a sensitive and high-resolution imaging modality for bladder cancer, we have developed a photoacoustic imaging approach based on the use of PEGylated gold nanorods (GNRs) as a contrast agent, functionalized with the peptide cyclic [CphgisoDGRG] (Iso4), a selective ligand of α5ß1 integrin expressed by bladder cancer cells. This product (called GNRs@PEG-Iso4) was produced by a simple two-step procedure based on GNRs activation with lipoic acid-polyethyleneglycol(PEG-5KDa)-maleimide and functionalization with peptide Iso4. Biochemical and biological studies showed that GNRs@PEG-Iso4 can efficiently recognize purified integrin α5ß1 and α5ß1-positive bladder cancer cells. GNRs@PEG-Iso4 was stable and did not aggregate in urine or in 5% sodium chloride, or after freeze/thaw cycles or prolonged exposure to 55 °C, and, even more importantly, do not settle after instillation into the bladder. Intravesical instillation of GNRs@PEG-Iso4 into mice bearing orthotopic MB49-Luc bladder tumors, followed by photoacoustic imaging, efficiently detected small cancer lesions. The binding to tumor lesions was competed by a neutralizing anti-α5ß1 integrin antibody; furthermore, no binding was observed to healthy bladders (α5ß1-negative), pointing to a specific targeting mechanism. CONCLUSION: GNRs@PEG-Iso4 represents a simple and robust contrast agent for photoacoustic imaging and diagnosis of small bladder cancer lesions.

Dual Source Photon-Counting Computed Tomography-Part II: Clinical Overview of Neurovascular Applications.

Photon-counting detector (PCD) is a novel computed tomography detector technology (photon-counting computed tomography-PCCT) that presents many advantages in the neurovascular field, such as increased spatial resolution, reduced radiation exposure, and optimization of the use of contrast agents and material decomposition. In this overview of the existing literature on PCCT, we describe the physical principles, the advantages and the disadvantages of conventional energy integrating detectors and PCDs, and finally, we discuss the applications of the PCD, focusing specifically on its implementation in the neurovascular field.

Dual-Source Photon-Counting Computed Tomography-Part I: Clinical Overview of Cardiac CT and Coronary CT Angiography Applications.

The photon-counting detector (PCD) is a new computed tomography detector technology (photon-counting computed tomography, PCCT) that provides substantial benefits for cardiac and coronary artery imaging. Compared with conventional CT, PCCT has multi-energy capability, increased spatial resolution and soft tissue contrast with near-null electronic noise, reduced radiation exposure, and optimization of the use of contrast agents. This new technology promises to overcome several limitations of traditional cardiac and coronary CT angiography (CCT/CCTA) including reduction in blooming artifacts in heavy calcified coronary plaques or beam-hardening artifacts in patients with coronary stents, and a more precise assessment of the degree of stenosis and plaque characteristic thanks to its better spatial resolution. Another potential application of PCCT is the use of a double-contrast agent to characterize myocardial tissue. In this current overview of the existing PCCT literature, we describe the strengths, limitations, recent applications, and promising developments of employing PCCT technology in CCT.

Dual-Source Photon-Counting Computed Tomography-Part III: Clinical Overview of Vascular Applications beyond Cardiac and Neuro Imaging.

Photon-counting computed tomography (PCCT) is an emerging technology that is expected to radically change clinical CT imaging. PCCT offers several advantages over conventional CT, which can be combined to improve and expand the diagnostic possibilities of CT angiography. After a brief description of the PCCT technology and its main advantages we will discuss the new opportunities brought about by PCCT in the field of vascular imaging, while addressing promising future clinical scenarios.

Extracellular Vesicles and Intercellular Communication: Challenges for In Vivo Molecular Imaging and Tracking.

Extracellular vesicles (EVs) are a heterogeneous class of cell-derived membrane vesicles released by various cell types that serve as mediators of intercellular signaling. When released into circulation, EVs may convey their cargo and serve as intermediaries for intracellular communication, reaching nearby cells and possibly also distant organs. In cardiovascular biology, EVs released by activated or apoptotic endothelial cells (EC-EVs) disseminate biological information at short and long distances, contributing to the development and progression of cardiovascular disease and related disorders. The significance of EC-EVs as mediators of cell-cell communication has advanced, but a thorough knowledge of the role that intercommunication plays in healthy and vascular disease is still lacking. Most data on EVs derive from in vitro studies, but there are still little reliable data available on biodistribution and specific homing EVs in vivo tissues. Molecular imaging techniques for EVs are crucial to monitoring in vivo biodistribution and the homing of EVs and their communication networks both in basal and pathological circumstances. This narrative review provides an overview of EC-EVs, trying to highlight their role as messengers of cell-cell interaction in vascular homeostasis and disease, and describes emerging applications of various imaging modalities for EVs visualization in vivo.

In Vivo Analysis of a Biodegradable Magnesium Alloy Implant in an Animal Model Using Near-Infrared Spectroscopy.

Biodegradable magnesium-based implants offer mechanical properties similar to natural bone, making them advantageous over nonbiodegradable metallic implants. However, monitoring the interaction between magnesium and tissue over time without interference is difficult. A noninvasive method, optical near-infrared spectroscopy, can be used to monitor tissue's functional and structural properties. In this paper, we collected optical data from an in vitro cell culture medium and in vivo studies using a specialized optical probe. Spectroscopic data were acquired over two weeks to study the combined effect of biodegradable Mg-based implant disks on the cell culture medium in vivo. Principal component analysis (PCA) was used for data analysis. In the in vivo study, we evaluated the feasibility of using the near-infrared (NIR) spectra to understand physiological events in response to magnesium alloy implantation at specific time points (Day 0, 3, 7, and 14) after surgery. Our results show that the optical probe can detect variations in vivo from biological tissues of rats with biodegradable magnesium alloy "WE43" implants, and the analysis identified a trend in the optical data over two weeks. The primary challenge of in vivo data analysis is the complexity of the implant interaction near the interface with the biological medium.

Near-Infrared Spectroscopy for the In Vivo Monitoring of Biodegradable Implants in Rats.

Magnesium (Mg) alloys possess unique properties that make them ideal for use as biodegradable implants in clinical applications. However, reports on the in vivo assessment of these alloys are insufficient. Thus, monitoring the degradation of Mg and its alloys in vivo is challenging due to the dynamic process of implant degradation and tissue regeneration. Most current works focus on structural remodeling, but functional assessment is crucial in providing information about physiological changes in tissues, which can be used as an early indicator of healing. Here, we report continuous wave near-infrared spectroscopy (CW NIRS), a non-invasive technique that is potentially helpful in assessing the implant-tissue dynamic interface in a rodent model. The purpose of this study was to investigate the effects on hemoglobin changes and tissue oxygen saturation (StO2) after the implantation of Mg-alloy (WE43) and titanium (Ti) implants in rats' femurs using a multiwavelength optical probe. Additionally, the effect of changes in the skin on these parameters was evaluated. Lastly, combining NIRS with photoacoustic (PA) imaging provides a more reliable assessment of tissue parameters, which is further correlated with principal component analysis.

Gold nanorods assisted photothermal therapy of bladder cancer in mice: A computational study on the effects of gold nanorods distribution at the centre, periphery, and surface of bladder cancer.

BACKGROUND AND OBJECTIVES: Gold nanorod-assisted photothermal therapy (GNR-PTT) is a cancer treatment whereby GNRs incorporated into the tumour act as photo-absorbers to elevate the thermal destruction effect. In the case of bladder, there are few possible routes to target the tumour with GNRs, namely peri/intra-tumoural injection and intravesical instillation of GNRs. These two approaches lead to different GNR distribution inside the tumour and can affect the treatment outcome. METHODOLOGY: The present study investigates the effects of heterogeneous GNR distribution in a typical setup of GNR-PTT. Three cases were considered. Case 1 considered the GNRs at the tumour centre, while Case 2 represents a hypothetical scenario where GNRs are distributed at the tumour periphery; these two cases represent intratumoural accumulation with different degree of GNR spread inside the tumour. Case 3 is achieved when GNRs target the exposed tumoural surface that is invading the bladder wall, when they are delivered by intravesical instillation. RESULTS: Results indicate that for a laser power of 0.6 W and GNR volume fraction of 0.01%, Case 2 and 3 were successful in achieving complete tumour eradication after 330 and 470 s of laser irradiation, respectively. Case 1 failed to form complete tumour damage when the GNRs are concentrated at the tumour centre but managed to produce complete tumour damage if the spread of GNRs is wider. Results from Case 2 also demonstrated a different heating profile from Case 1, suggesting that thermal ablation during GNR-PTT is dependant on the GNRs distribution inside the tumour. Case 3 shows similar results to Case 2 whereby gradual but uniform heating is observed. Cases 2 and 3 show that uniformly heating the tumour can reduce damage to the surrounding tissues. CONCLUSIONS: Different GNR distribution associated with the different methods of introducing GNRs to the bladder during GNR-PTT affect the treatment outcome of bladder cancer in mice. Insufficient spreading during intratumoural injection of GNRs can render the treatment ineffective, while administered via intravesical instillation. GNR distribution achieved through intravesical instillation present some advantages over intratumoural injection and is worthy of further exploration.

Shaping and Focusing Magnetic Field in the Human Body: State-of-the Art and Promising Technologies.

In recent years, the usage of radio frequency magnetic fields for biomedical applications has increased exponentially. Several diagnostic and therapeutic methodologies exploit this physical entity such as, for instance, magnetic resonance imaging, hyperthermia with magnetic nanoparticles and transcranial magnetic stimulation. Within this framework, the magnetic field focusing and shaping, at different depths inside the tissue, emerges as one of the most important challenges from a technological point of view, since it is highly desirable for improving the effectiveness of clinical methodologies. In this review paper, we will first report some of the biomedical practices employing radio frequency magnetic fields, that appear most promising in clinical settings, explaining the underneath physical principles and operative procedures. Specifically, we direct the interest toward hyperthermia with magnetic nanoparticles and transcranial magnetic stimulation, together with a brief mention of magnetic resonance imaging. Additionally, we deeply review the technological solutions that have appeared so far in the literature to shape and control the radio frequency magnetic field distribution within biological tissues, highlighting human applications. In particular, volume and surface coils, together with the recent raise of metamaterials and metasurfaces will be reported. The present review manuscript can be useful to fill the actual gap in the literature and to serve as a guide for the physicians and engineers working in these fields.

Synthesis and Characterization of Multifunctional Nanovesicles Composed of POPC Lipid Molecules for Nuclear Imaging.

The integration of nuclear imaging analysis with nanomedicine has tremendously grown and represents a valid and powerful tool for the development and clinical translation of drug delivery systems. Among the various types of nanostructures used as drug carriers, nanovesicles represent intriguing platforms due to their capability to entrap both lipophilic and hydrophilic agents, and their well-known biocompatibility and biodegradability. In this respect, here we present the development of a labelling procedure of POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine)-based liposomes incorporating an ad hoc designed lipophilic NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid) analogue, derivatized with an oleic acid residue, able to bind the positron emitter gallium-68(III). Based on POPC features, the optimal conditions for liposome labelling were studied with the aim of optimizing the Ga(III) incorporation and obtaining a significant radiochemical yield. The data presented in this work demonstrate the feasibility of the labelling procedure on POPC liposomes co-formulated with the ad hoc designed NOTA analogue. We thus provided a critical insight into the practical aspects of the development of vesicles for theranostic approaches, which in principle can be extended to other nanosystems exploiting a variety of bioconjugation protocols.

Controlled Release of Doxorubicin for Targeted Chemo-Photothermal Therapy in Breast Cancer HS578T Cells Using Albumin Modified Hybrid Nanocarriers.

Hybrid nanomaterials have attracted research interest owing to their intriguing properties, which may offer new diagnostic options with triggering features, able to realize a new kind of tunable nanotherapeutics. Hybrid silica/melanin nanoparticles (NPs) containing silver seeds (Me-laSil_Ag-HSA NPs) disclosed relevant photoacoustic contrast for molecular imaging. In this study we explored therapeutic function in the same nanoplatform. For this purpose, MelaSil_Ag-HSA were loaded with doxorubicin (DOX) (MelaSil_Ag-HSA@DOX) and tested to assess the efficiency of drug delivery combined with concurrent photothermal treatment. The excellent photothermal properties allowed enhanced cytotoxic activity at significantly lower doses than neat chemotherapeutic treatment. The results revealed that MelaSil_Ag-HSA@DOX is a promising platform for an integrated photothermal (PT) chemotherapy approach, reducing the efficacy concentration of the DOX and, thus, potentially limiting the several adverse side effects of the drug in in vivo treatments.

A numerical study to investigate the effects of tumour position on the treatment of bladder cancer in mice using gold nanorods assisted photothermal ablation.

Gold nanorods assisted photothermal therapy (GNR-PTT) is a new cancer treatment technique that has shown promising potential for bladder cancer treatment. The position of the bladder cancer at different locations along the bladder wall lining can potentially affect the treatment efficacy since laser is irradiated externally from the skin surface. The present study investigates the efficacy of GNR-PTT in the treatment of bladder cancer in mice for tumours growing at three different locations on the bladder, i.e., Case 1: closest to skin surface, Case 2: at the bottom half of the bladder, and Case 3: at the side of the bladder. Investigations were carried out numerically using an experimentally validated framework for optical-thermal simulations. An in-silico approach was adopted due to the flexibility in placing the tumour at a desired location along the bladder lining. Results indicate that for the treatment parameters considered (laser power 0.3 W, GNR volume fraction 0.01% v/v), only Case 1 can be used for an effective GNR-PTT. No damage to the tumour was observed in Cases 2 and 3. Analysis of the thermo-physiological responses showed that the effectiveness of GNR-PTT in treating bladder cancer depends not only on the depth of the tumour from the skin surface, but also on the type of tissue that the laser must pass through before reaching the tumour. In addition, the results are reliant on GNRs with a diameter of 10 nm and an aspect ratio of 3.8 - tuned to exhibit peak absorption for the chosen laser wavelength. Results from the present study can be used to highlight the potential for using GNR-PTT for treatment of human bladder cancer. It appears that Cases 2 and 3 suggest that GNR-PTT, where the laser passes through the skin to reach the bladder, may be unfeasible in humans. While this study shows the feasibility of using GNRs for photothermal ablation of bladder cancer, it also identifies the current limitations needed to be overcome for an effective clinical application in the bladder cancer patients.

In Vivo Imaging of Biodegradable Implants and Related Tissue Biomarkers.

Non-invasive longitudinal imaging of osseointegration of bone implants is essential to ensure a comprehensive, physical and biochemical understanding of the processes related to a successful implant integration and its long-term clinical outcome. This study critically reviews the present imaging techniques that may play a role to assess the initial stability, bone quality and quantity, associated tissue remodelling dependent on implanted material, implantation site (surrounding tissues and placement depth), and biomarkers that may be targeted. An updated list of biodegradable implant materials that have been reported in the literature, from metal, polymer and ceramic categories, is provided with reference to the use of specific imaging modalities (computed tomography, positron emission tomography, ultrasound, photoacoustic and magnetic resonance imaging) suitable for longitudinal and non-invasive imaging in humans. The advantages and disadvantages of the single imaging modality are discussed with a special focus on preclinical imaging for biodegradable implant research. Indeed, the investigation of a new implant commonly requires histological examination, which is invasive and does not allow longitudinal studies, thus requiring a large number of animals for preclinical testing. For this reason, an update of the multimodal and multi-parametric imaging capabilities will be here presented with a specific focus on modern biomaterial research.