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Traditional bone tissue engineering (BTE) strategies induce direct bone-like matrix formation by mimicking the embryological process of intramembranous ossification. However, the clinical translation of these clinical strategies for bone repair is hampered by limited vascularization and poor bone regeneration after implantation in vivo. An alternative strategy for overcoming these drawbacks is engineering cartilaginous constructs by recapitulating the embryonic processes of endochondral ossification (ECO); these constructs have shown a unique ability to survive under hypoxic conditions as well as induce neovascularization and ossification. Such developmentally engineered constructs can act as transient biomimetic templates to facilitate bone regeneration in critical-sized defects. This review introduces the concept and mechanism of developmental BTE, explores the routes of endochondral bone graft engineering, highlights the current state of the art in large bone defect reconstruction via ECO-based strategies, and offers perspectives on the challenges and future directions of translating current knowledge from the bench to the bedside.

Severe tracheal injuries that cannot be managed by mobilization and end-to-end anastomosis represent an unmet clinical need and an urgent challenge to face in surgical practice; within this scenario, decellularized scaffolds (eventually bioengineered) are currently a tempting option among tissue engineered substitutes. The success of a decellularized trachea is expression of a balanced approach in cells removal while preserving the extracellular matrix (ECM) architecture/mechanical properties. Revising the literature, many Authors report about different methods for acellular tracheal ECMs development; however, only few of them verified the devices effectiveness by an orthotopic implant in animal models of disease. To support translational medicine in this field, here we provide a systematic review on studies recurring to decellularized/bioengineered tracheas implantation. After describing the specific methodological aspects, orthotopic implant results are verified. Furtherly, the only three clinical cases of compassionate use of tissue engineered tracheas are reported with a focus on outcomes.

Spinal fusion has become a common surgical technique to join two or more vertebrae to stabilize a damaged spine; however, the rate of pseudarthrosis (failure of fusion) is still high. To minimize pseudarthrosis, bone morphogenetic protein-2 (BMP2) has been approved for use in humans. In this study, we developed a poly(lactide-co-glycolide) (PLGA) composite incorporated with magnesium hydroxide (MH) nanoparticles for the delivery of BMP2. This study aimed to evaluate the effects of released BMP2 from BMP2-immobilized PLGA/MH composite scaffold in an in vitro test and an in vivo mice spinal fusion model. The PLGA/MH composite films were fabricated via solvent casting technique. The surface of the PLGA/MH composite scaffold was modified with polydopamine (PDA) to effectively immobilize BMP2 on the PLGA/MH composite scaffold. Analyzes of the scaffold revealed that using PLGA/MH-PDA improved hydrophilicity, degradation performance, neutralization effects, and increased BMP2 loading efficiency. In addition, releasing BMP2 from the PLGA/MH scaffold significantly promoted the proliferation and osteogenic differentiation of MC3T3-E1 cells. Furthermore, the pH neutralization effect significantly increased in MC3T3-E1 cells cultured on the BMP2-immobilized PLGA/MH scaffold. In our animal study, the PLGA/MH scaffold as a BMP2 carrier attenuates inflammatory responses and promotes BMP2-induced bone formation in posterolateral spinal fusion model. These results collectively demonstrate that the BMP2-immobilized PLGA/MH scaffold offers great potential in effectively inducing bone formation in spinal fusion surgery.

The development of advanced in vitro models for assessing liver toxicity and drug responses is crucial for personalized medicine and preclinical drug development. 3D bioprinting technology provides opportunities to create human liver models that are suitable for conducting high-throughput screening for liver toxicity. In this study, we fabricated a humanized liver model using human-induced hepatocytes (hiHeps) derived from human fibroblasts via a rapid and efficient reprogramming process. These hiHeps were then employed in 3D bioprinted liver models with bioink materials that closely mimic the natural extracellular matrix. The constructed humanized 3D bioprinted livers (h3DPLs) exhibited mature hepatocyte functions, including albumin expression, glycogen storage, and uptake/release of indocyanine green and acetylated low-density lipoprotein. Notably, h3DPLs demonstrated increased sensitivity to hepatotoxic agents such as acetaminophen (APAP), making them a promising platform for studying drug-induced liver injury. Furthermore, our model accurately reflected the impact of rifampin, a cytochrome P450 inducer, on CYP2E1 levels and APAP hepatotoxicity. These results highlight the potential of hiHep-based h3DPLs as a cost-effective and high-performance alternative for personalized liver toxicity screening and preclinical drug testing, paving the way for improved drug development strategies and personalized therapeutic interventions.

There have been remarkable advancements in regenerative medicine for bone regeneration, tackling the worldwide health concern of tissue loss. Tissue engineering uses the body’s natural capabilities and applies biomaterials and bioactive molecules to replace damaged or lost tissues and restore their functionality. While synthetic ceramics have overcome some challenges associated with allografts and xenografts, they still need essential growth factors and biomolecules. Combining ceramics and bioactive molecules, such as peptides derived from biological motifs of vital proteins, is the most effective approach to achieve optimal bone regeneration. These bioactive peptides induce various cellular processes and modify scaffold properties by mimicking the function of natural osteogenic, angiogenic and antibacterial biomolecules. The present review aims to consolidate the latest and most pertinent information on the advancements in bioactive peptides, including angiogenic, osteogenic, antimicrobial, and self-assembling peptide nanofibers for bone tissue regeneration, elucidating their biological effects and potential clinical implications.

By integrating 3D-inkjet bioprinting technology, differentiated human cells can be assembled into artificial lung tissue structure to achieve a rapid, efficient, and reproducible disease model construction process. Here, we developed a novel 3D-inkjet bioprinting-based method to construct artificial lung tissue structure (ALTs) for acute lung injury (ALI) disease modeling, research and application. It can also be used to study the role of relevant cells in the disease by adjusting the cell type and adapted to study the bio-functions of immune cells during the cell-cell interactions. Firstly, a series of process optimizations were done to mass-produce the alginate hydrogel microspheres (Alg) with a particle size of 262.63 ± 5 μm using a 3D bioprinter, then the type I collagen and polydopamine were deposited in turns to construct a cell adhesion layer on the surfaces of Alg (P-Alg) and the particle size was increased to 328.41 ± 3.81 μm. This platform exhibites good stability, timescale-dependent behavior, and long-term cell adhesion. Subsequently, several human cells including endothelial, epithelial, fibroblast, and even immune cells such as macrophages were adhered to P-Alg through rotational culture, leading to cell contractions and aggregation, subsequently formed ALTs or ALTs with macrophages (ALTs@M) with human alveolar-like structure. Finally, we successfully constructed an ALI model with lung barrier damage on ALTs using lipopolysaccharide stimulation in vitro, and comparison of secreted inflammatory factors between ALTs and ALTs@M. Results demonstrated that ALTs@M was more effective than ALTs in stimulating the inflammatory microenvironment of the lungs, providing a novel in vitro model for cellular interactions and human macrophage research. Altogether, this artificial lung tissue structure construction strategy using 3D-inkjet bioprinting technology allowed the flexible development of artificial lung tissue structures as potential disease models for preclinical studies.

Liver transplantation is the only definitive treatment for many diseases that affect this organ, however, its quantity and viability are reduced. The study of liver scaffolds based on an extracellular matrix is a tissue bioengineering strategy with great application in regenerative medicine. Collectively, recent studies suggest that liver scaffold transplantation may assist in reestablishing hepatic function in preclinical diseased animals, which represents a great potential for application as a treatment for patients with liver disease in the future. This review focuses on useful strategies to promote liver scaffold transplantation and the main open questions about this context. We outline the current knowledge about ex vivo bioengineered liver transplantation, including the surgical techniques, recipient survival time, scaffold preparation before transplantation, and liver disease models. We also highlight the current limitations and future directions regarding in vivo bioengineering techniques.

In biology and medicine, intrinsically disordered synthetic polymers bio-mimicking intrinsically disordered proteins, which lack stable three-dimensional structures, possess high structural/conformational flexibility. They are prone to self-organization and can be extremely useful in various biomedical applications. Among such applications, intrinsically disordered synthetic polymers can have potential usage in drug delivery, organ transplantation, artificial organ design, and immune compatibility. The designing of new syntheses and characterization mechanisms is currently required to provide the lacking intrinsically disordered synthetic polymers for biomedical applications bio-mimicked using intrinsically disordered proteins. Here, we present our strategies for designing intrinsically disordered synthetic polymers for biomedical applications based on bio-mimicking intrinsically disordered proteins.

Fibrous scaffolds have shown their advantages in tissue engineering, such as peripheral nerve regeneration, while most of the existing fiber‐shaped scaffolds are with simple structures, and the in vitro performance for nerve regeneration lacks systematic analysis. Here, novel nerve‐on‐a‐chip derived biomimicking microfibers for peripheral nerve regeneration are presented. The microfibers with controllable core–shell structures and functionalities are generated through capillary microfluidic devices. By integrating these microfibers into a multitrack‐architectured chip, and coculturing them with nerve cells as well as gradient bioactive elements, the nerve‐on‐a‐chip with the capabilities of systematically assessing the performances of nerve fiber formation in the hollow microfibers at in vitro level is constructed. Based on a rat sciatic nerve injury model, the rapid promotion ability is demonstrated of optimized microfibers in nerve regeneration and function recovery in vivo, which implies the credibility of the nerve‐on‐a‐chip on biomimicking microfibers evaluation for peripheral nerve regeneration. Thus, it is convinced that the organ‐on‐a‐chip will undoubtedly open up a new chapter in evaluating biological scaffolds for in vivo tissue engineering. Microfibers with desired structures are generated and integrated into a chip with multitrack, cocultured with nerve cells and gradient extracellular matrixes to form the nerve‐on‐a‐chip. The nerve‐on‐a‐chip is able to systematically compare and assess the performances of nerve fiber formation in the hollow microfibers at in vitro level. A rat sciatic nerve injury model is used to demonstrate its credible assessing and screening ability.