Polymeric drug delivery systems (PDDS) play a crucial role in controlled drug release, providing improved therapeutic outcomes. However, formulating PDDS and predicting their release profiles remain challenging due to their complex structures and the numerous variables that influence their behavior. Traditional mathematical and empirical prediction methods are limited in capturing these complexities. Recent studies have unveiled the potential of Machine Learning (ML) in revolutionizing drug delivery, particularly in formulating complex PDDS. This article provides an overview of the significant and fundamental principles of various ML strategies in estimating PDDS drug release behavior. Our focus extends to the accomplishments and pivotal discoveries in current research, spanning seven distinct sustained-release drug delivery systems: matrix tablets, microspheres, implants, hydrogels, films, 3D-printed dosage forms, and other innovations. Furthermore, it addresses the challenges associated with ML-based drug release prediction and presents current solutions while delving into future perspectives. Our investigation underscores the significance of Artificial Neural Networks in ML-based PDDS release profile prediction, surpassing both traditional and alternative ML-based methods. These extensive datasets can be drawn from literature-based resources or enhanced through specific algorithms. Moreover, ensemble-based models have proven advantageous in scenarios involving intricate relationships, such as a high number of output parameters. ML-based drug release prediction notably exhibits substantial promise in 3D-printed dosage forms, presenting a frontier for personalized medicine and precise drug delivery.

Bone defects from accidents, congenital conditions, and age-related diseases significantly impact quality of life. Recent advancements in bone tissue engineering (TE) involve biomaterial scaffolds, patient-derived cells, and bioactive agents, enabling functional bone regeneration. Stem cells, obtained from numerous sources including umbilical cord blood, adipose tissue, bone marrow, and dental pulp, hold immense potential in bone TE. Induced pluripotent stem cells and genetically modified stem cells can also be used. Proper manipulation of physical, chemical, and biological stimulation is crucial for their proliferation, maintenance, and differentiation. Stem cells contribute to osteogenesis, osteoinduction, angiogenesis, and mineralization, essential for bone regeneration. This review provides an overview of the latest developments in stem cell-based TE for repairing and regenerating defective bones.

Oxygen (O2), nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H2S), and hydrogen (H2) with direct effects, and carbon dioxide (CO2) with complementary effects on the condition of various diseases are known as therapeutic gases. The targeted delivery and in situ generation of these therapeutic gases with controllable release at the site of disease has attracted attention to avoid the risk of gas poisoning and improve their performance in treating various diseases such as cancer therapy, cardiovascular therapy, bone tissue engineering, and wound healing. Stimuli-responsive gas-generating sources and delivery systems based on biomaterials that enable on-demand and controllable release are promising approaches for precise gas therapy. This work highlights current advances in the design and development of new approaches and systems to generate and deliver therapeutic gases at the site of disease with on-demand release behavior. The performance of the delivered gases in various biomedical applications is then discussed.

Mesenchymal stem/stromal cells are potential optimal cell sources for stem cell therapies, and pretreatment has proven to enhance cell vitality and function. In a recent publication, Li et al explored a new combination of pretreatment conditions. Here, we present an editorial to comment on their work and provide our view on mesenchymal stem/stromal cell precondition.

The use of nanoparticle systems for the controlled release of growth factors is a promising approach to mimicking of the biochemical environment of native tissues in tissue engineering. However, sustaining growth factor release inside an appropriate therapeutic window is a challenge, particularly in bioprinted scaffolds. In this study, a chitosan-coated alginate-based nanoparticle system loaded with hepatocyte growth factor was developed and then incorporated into bioprinted scaffolds. The release kinetics were investigated with a focus on identifying the impact of the chitosan coating and culture conditions. Our results demonstrated that the chitosan coating decreased the release rate and lessened the initial burst release, while culturing in dynamic conditions had no significant impact compared to static conditions. The nanoparticles were then incorporated into bioinks at various concentrations, and scaffolds with a three-dimensional (3D) structure were bioprinted from the bioinks containing human pulmonary fibroblasts and bronchial epithelial cells to investigate the potential use of a controlled release system in respiratory tissue engineering. It was found that the bioink loaded with a concentration of 4 µg/mL of nanoparticles had better printability compared to other concentrations, while the mechanical stability of the scaffolds was maintained over a 14-day culture period. The examination of the incorporated cells demonstrated a high degree of viability and proliferation with visualization of the beginning of an epithelial barrier layer. Taken together, this study demonstrates that a chitosan-coated alginate-based nanoparticle system allows the sustained release of growth factors in bioprinted respiratory tissue scaffolds.

Three-dimensional (3D) printing is a promising approach for the stabilization and delivery of non-living biologics. This versatile tool builds complex structures and customized resolutions, and has significant potential in various industries, especially pharmaceutics and biopharmaceutics. Biologics have become increasingly prevalent in the field of medicine due to their diverse applications and benefits. Stability is the main attribute that must be achieved during the development of biologic formulations. 3D printing could help to stabilize biologics by entrapment, support binding, or crosslinking. Furthermore, gene fragments could be transited into cells during co-printing, when the pores on the membrane are enlarged. This review provides: (i) an introduction to 3D printing technologies and biologics, covering genetic elements, therapeutic proteins, antibodies, and bacteriophages; (ii) an overview of the applications of 3D printing of biologics, including regenerative medicine, gene therapy, and personalized treatments; (iii) information on how 3D printing could help to stabilize and deliver biologics; and (iv) discussion on regulations, challenges, and future directions, including microneedle vaccines, novel 3D printing technologies and artificial-intelligence-facilitated research and product development. Overall, the 3D printing of biologics holds great promise for enhancing human health by providing extended longevity and enhanced quality of life, making it an exciting area in the rapidly evolving field of biomedicine.

The limited availability of transplantable organs hinders the success of patient treatment through organ transplantation. In addition, there are challenges with immune rejection and the risk of disease transmission when receiving organs from other individuals. Tissue engineering aims to overcome these challenges by generating functional three-dimensional (3D) tissue constructs. When developing tissues or organs of a particular shape, structure, and size as determined by the specific needs of the therapeutic intervention, a tissue specific oxygen supply to all parts of the tissue construct is an utmost requirement. Moreover, the lack of a functional vasculature in engineered tissues decreases cell survival upon implantation in the body. Oxygen-generating materials can alleviate this challenge in engineered tissue constructs by providing oxygen in a sustained and controlled manner. Oxygen-generating materials can be incorporated into 3D scaffolds allowing the cells to receive and utilize oxygen efficiently. In this review, we present an overview of the use of oxygen-generating materials in various tissue engineering applications in an organ specific manner as well as their potential use in the clinic.

The shape transformation characteristics of four-dimensional (4D)-printed bone structures can meet the individual bone regeneration needs, while their structure can be programmed to cross-link or reassemble by stimulating responsive materials. At the same time, it can be used to design vascularized bone structures that help establish a bionic microenvironment, thus influencing cellular behavior and enhancing stem cell differentiation in the postprinting phase. These developments significantly improve conventional three-dimensional (3D)-printed bone structures with enhanced functional adaptability, providing theoretical support to fabricate bone structures to adapt to defective areas dynamically. The printing inks used are stimulus-responsive materials that enable spatiotemporal distribution, maintenance of bioactivity and cellular release for bone, vascular and neural tissue regeneration. This paper discusses the limitations of current bone defect therapies, 4D printing materials used to stimulate bone tissue engineering (e.g., hydrogels), the printing process, the printing classification and their value for clinical applications. We focus on summarizing the technical challenges faced to provide novel therapeutic implications for bone defect repair.