With advantageous features such as minimizing the cost, time, and sample size requirements, organ-on-a-chip (OOC) systems have garnered enormous interest from researchers for their ability for real-time monitoring of physical parameters by mimicking the in vivo microenvironment and the precise responses of xenobiotics, i.e., drug efficacy and toxicity over conventional two-dimensional (2D) and three-dimensional (3D) cell cultures, as well as animal models. Recent advancements of OOC systems have evidenced the fabrication of ‘multi-organ-on-chip’ (MOC) models, which connect separated organ chambers together to resemble an ideal pharmacokinetic and pharmacodynamic (PK-PD) model for monitoring the complex interactions between multiple organs and the resultant dynamic responses of multiple organs to pharmaceutical compounds. Numerous varieties of MOC systems have been proposed, mainly focusing on the construction of these multi-organ models, while there are only few studies on how to realize continual, automated, and stable testing, which still remains a significant challenge in the development process of MOCs. Herein, this review emphasizes the recent advancements in realizing long-term testing of MOCs to promote their capability for real-time monitoring of multi-organ interactions and chronic cellular reactions more accurately and steadily over the available chip models. Efforts in this field are still ongoing for better performance in the assessment of preclinical attributes for a new chemical entity. Further, we give a brief overview on the various biomedical applications of long-term testing in MOCs, including several proposed applications and their potential utilization in the future. Finally, we summarize with perspectives.

Attempts to reflect the physiology of organs is quite an intricacy during the tissue engineering process. An ideal scaffold and its surface topography can address and manipulate the cell behavior during the regeneration of targeted tissue, affecting the cell growth and differentiation significantly. Herein, silk fibroin (SF) nanoparticles were incorporated into poly(L-lactic acid) (PLLA) to prepare composite scaffolds via phase-inversion technique using supercritical carbon dioxide (SC-CO₂). The SF nanoparticle core increased the surface roughness and hydrophilicity of the PLLA scaffolds, leading to a high affinity for albumin attachment. The in vitro cytotoxicity test of SF/PLLA scaffolds in L929 mouse fibroblast cells indicated good biocompatibility. Then, the in vitro interplay between mouse preosteoblast cell (MC3T3-E1) and various topological structures and biochemical cues were evaluated. The cell adhesion, proliferation, osteogenic differentiation and their relationship with the structures as well as SF content were explored. The SF/PLLA weight ratio (2:8) significantly affected the MC3T3-E1 cells by improving the expression of key players in the regulation of bone formation, ie, alkaline phosphatase (ALP), osteocalcin (OC) and collagen 1 (COL-1). These results suggest not only the importance of surface topography and biochemical cues but also the potential of applying SF/PLLA composite scaffolds as biomaterials in bone tissue engineering.

In recent times, tremendous progress has been evidenced by the advancements in various methods of generating three-dimensional (3D) porous scaffolds. However, the applicability of most of the traditional approaches intended for generating these biomimetic scaffolds is limited due to poor resolution and strict requirements in choosing materials. In this work, we fabricated 3D porous scaffolds based on the composite inks of gelatin (Gel), nano-hydroxyapatite (n-HA), and poly(lactide-co-glycolide) (PLGA) using an innovative hybrid strategy based on 3D printing and freeze-drying technologies for bone tissue engineering. Initially, the PLGA scaffolds were printed using the 3D printing method, and they were then coated with the Gel/n-HA complex, yielding the Gel/n-HA/PLGA scaffolds. These Gel/n-HA/PLGA scaffolds with exceptional biodegradation, mechanical properties, and biocompatibility have enabled osteoblasts (MC3T3-E1) for their convenient adhesion as a layer and have efficiently promoted their growth, as well as differentiation. We further demonstrated the bone growth by measuring the particular biomarkers that act as key players in the ossification process (i.e., alkaline phosphatase (ALP), osteocalcin (OC), and collagen type-I (COL-I)) and the total proteins of the MC3T3-E1 cells. We anticipate that the convenient generation of highly porous 3D scaffolds based on Gel/n-HA/PLGA fabricated through an innovative combinatorial approach of 3D printing technology and freeze-drying methods may undoubtedly find widespread applications in regenerative medicine.

In recent times, photo-induced therapeutics have attracted enormous interest from researchers due to such attractive properties as preferential localization, excellent tissue penetration, high therapeutic efficacy, and minimal invasiveness, among others. Numerous photosensitizers have been considered in combination with light to realize significant progress in therapeutics. Along this line, indocyanine green (ICG), a Food and Drug Administration (FDA)-approved near-infrared (NIR, >750 nm) fluorescent dye, has been utilized in various biomedical applications such as drug delivery, imaging, and diagnosis, due to its attractive physicochemical properties, high sensitivity, and better imaging view field. However, ICG still suffers from certain limitations for its utilization as a molecular imaging probe in vivo, such as concentration-dependent aggregation, poor in vitro aqueous stability and photodegradation due to various physicochemical attributes. To overcome these limitations, much research has been dedicated to engineering numerous multifunctional polymeric composites for potential biomedical applications. In this review, we aim to discuss ICG-encapsulated polymeric nanoconstructs, which are of particular interest in various biomedical applications. First, we emphasize some attractive properties of ICG (including physicochemical characteristics, optical properties, metabolic features, and other aspects) and some of its current limitations. Next, we aim to provide a comprehensive overview highlighting recent reports on various polymeric nanoparticles that carry ICG for light-induced therapeutics with a set of examples. Finally, we summarize with perspectives highlighting the significant outcome, and current challenges of these nanocomposites.