Three-dimensional (3D) printing technology has revolutionized the design and fabrication of bone scaffolds, offering precise and customizable solutions for bone tissue engineering. In this study, we developed polycaprolactone (PCL) scaffolds that incorporated gold plasmonic blackbodies (AuPBs) to harness photothermal properties for temperature-controlled bone regeneration. The AuPB-PCL scaffolds demonstrated enhanced mechanical strength, a tunable thermal response under near-infrared (NIR) laser irradiation, and improved osteogenic potential. Photothermal stimulation effectively modulated cellular responses, promoting osteoblast proliferation, alkaline phosphatase (ALP) activity, and mineralization. Notably, mild hyperthermia (39-41 °C) induced by laser irradiation optimized osteogenesis, while excessive temperatures (≥42.5 °C) impaired cellular function due to mitochondrial stress and oxidative damage. These findings highlight the potential of AuPB-PCL scaffolds for controlled photothermal bone regeneration, offering a promising strategy for precise, completely noninvasive stimulation of bone repair.

The development of bioink-based 3D-printed scaffolds has revolutionized bone tissue engineering (BTE) by enabling patient-specific and biomimetic constructs for bone regeneration. This review focuses on the biocompatibility and mechanical properties essential for scaffold performance, highlighting advancements in bioink formulations, material combinations, and printing techniques. The key biomaterials, including natural polymers (gelatin, collagen, alginate), synthetic polymers (polycaprolactone, polyethylene glycol), and bioactive ceramics (hydroxyapatite, calcium phosphate), are discussed concerning their osteoconductivity, printability, and structural integrity. Despite significant progress, challenges remain in achieving optimal mechanical strength, degradation rates, and cellular interactions. The review explores emerging strategies such as gene-activated bioinks, nanocomposite reinforcements, and crosslinking techniques to enhance scaffold durability and bioactivity. By synthesizing recent developments, this work provides insights into future directions for bioink-based scaffolds, paving the way for more effective and personalized bone regenerative therapies.

Additive manufacturing (AM), also referred to as three-dimensional printing/printed (3DP), has emerged as a transformative approach in the current design and manufacturing of various biomaterials for the restoration of damaged tissues inside the body. This advancement has greatly aided the development of customized biomedical devices including implants, prosthetics, and orthotics that are specific to the patients. In tissue engineering (TE), AM enables the fabrication of complex structures that promote desirable cellular responses in the regeneration of tissues. Since the choice of biomaterials plays a vital role in scaffold performance as well as cellular responses, meticulous material selection is essential in optimizing the functionality of scaffolds. These scaffolds often possess certain characteristics such as biodegradability, biocompatibility, biomimicry, and porous structure. To this end, polymers such as chitosan, collagen, alginate, hyaluronic acid, polyglycolic acid, polylactic acid, and polycaprolactone have been extensively investigated in the fabrication of tissue-engineered scaffolds. Furthermore, combinations of biomaterials are also utilized to further enhance the scaffolds' performance and functionality. This review discusses the principle of AM and explores recent advancements in AM technologies in the development of TE and regenerative medicine. In addition, the applications of 3DP, polymer-based scaffolds will be highlighted.

As one of the 3D printing technologies, digital light processing (DLP) 3D printing technology has been widely applied in biomedical engineering. The principles and advantages of DLP 3D printing technology are compared with other 3D printing technologies, while the characteristics and applicable fields of each technique are analyzed. The applications of DLP 3D printing technology in tissue engineering, medical devices and pharmaceutical field are classified and summarized. Besides, the prospects and challenges of DLP 3D printing technology in biomedical engineering are discussed. With continuous advancement, DLP 3D printing technology will play an increasingly important role in personalized medicine and regenerative medicine.

Three-dimensional (3D) skin equivalents (SEs) are promising platforms for studying skin disease or assessing the safety of skin-relevant products. Vascularization, which improves the functionality of reconstructed skin, is one of the remaining hurdles in SE production that, when successfully introduced, can widen SE applications. Here, combining porous polycaprolactone (PCL) melt electrowritten (MEW) scaffolds with fibroblast-laden methacrylated gelatin hydrogel (GelMA), we developed SEs with cellular vascular structure. The MEW scaffolds were composed of two layers: random fibers for culturing the keratinocytes to fabricate the epidermis; and well-aligned shapes filled with fibroblast-laden GelMA to mimic the dermis. Three dermal designs varying in porosities and pore sizes were compared to optimize the dermis reconstruction. Within one week, the design with bigger pore sizes achieved optimal cell distribution, penetration, and extracellular matrix (ECM) deposition. Additionally, Retinoic acid (RTA) was tested for improving ECM deposition. To mimic vasculature, we incorporated vascular grafts into the optimized SEs. These were fabricated by casting endothelial fibroblast-laden Matrigel onto small-diameter MEW-tubular structures. The versatility and reproducibility of the obtained SEs offer a robust new tool for in vitro testing and exploration of fundamental biological processes of skin tissue.

Tissue engineering aims to repair damaged tissues with physiological functions recovery. Although several therapeutic strategies are there for tissue regeneration, the functional recovery of regenerated tissues still poses significant challenges due to the lack of concerns of tissue innervation. Design rationale of multifunctional biomaterials with both tissue-induction and neural induction activities shows great potential for functional tissue regeneration. Recently, the research and application of inorganic biomaterials attracts increasing attention in innervated multi-tissue regeneration, such as central nerves, bone, and skin, because of its superior tunable chemical composition, topographical structures, and physiochemical properties. More importantly, inorganic biomaterials are easily combined with other organic materials, biological factors, and external stimuli to enhance their therapeutic effects. This review presents a comprehensive overview of recent advancements of inorganic biomaterials for innervated multi-tissue regeneration. It begins with introducing classification and properties of typical inorganic biomaterials and design rationale of inorganic-based material composites. Then, recent progresses of inorganic biomaterials in regenerating various nerves and nerve-innervated tissues with functional recovery are systematically reviewed. Finally, the existing challenges and future perspectives are proposed. This review may pave the way for the direction of inorganic biomaterials and offers a new strategy for tissue regeneration in combination of innervation.

The most recent advances in bone tissue engineering (BTE) approaches step forward in the field of three-dimensional (3D) tissue models, enabling the development of more realistic tools to study bone disorders, such as osteoporosis. BTE field aims to mimic native bone tissue more truthfully, providing an appropriate environment for tissue regeneration and repair through the combination of 3D porous scaffolds, specific growth factors, and cells. Currently, the scientific community is focused on developing and improving new biomaterials that in combination with growth factors and specific cell types, that can accurately emulate the native bone microenvironment. However, most of the reported studies in the BTE field are focused on bone formation, disregarding the entire bone remodeling steps, which also involve bone resorption. In this review, the currently available mono and co-culturing methods, types of biomaterials used in several strategies that combine scaffolds and relevant cells (e.g., osteoblasts (OBs), osteoclasts (OCs), and osteocytes (OCys)), envisioning a healthy bone formation and remodeling process, the gold-standard drug delivery systems, and bioengineered-based systems to tackle bone diseases are described.

Printed form of polymeric nanomaterials in formation, crosslinking, structure, properties, toxicity and biocompatibility refers to the application of nanotechnology and 3D printing techniques to fabricate polymeric nanomaterials with specific physicochemical and biomedical features. In this regard, applications of 3D printing techniques, specifically for production of 3D scaffold have received huge attention in diabetes and bacterial infections. This review has tried to address recent advances and challenges related to applications of biocompatible polymeric nanomaterials in 3D printing techniques to ameliorate bacterial infections and diabetes. The applications of metal/metal oxide such as silver, gold, zinc, and titanium dioxide, and polymeric nanoparticles can augment the antimicrobial and degradation characteristics of 3D-printed scaffolds. The rapid advancements in 3D bio-printed scaffolds, specifically by artificial intelligence (AI) present a transformative landscape for diabetes treatment, addressing the complex challenges associated with impaired wound healing and tissue regeneration in individuals with diabetes mellitus.

In vitromodeling of vascular diseases provides a useful platform for drug screening and mechanistic studies, by recapitulating the essential structures and physiological characteristics of the native tissue. Bioprinting is an emerging technique that offers high-resolution 3D capabilities, which have recently been employed in the modeling of various tissues and associated diseases. Blood vessels are composed of multiple layers of distinct cell types, and experience different mechanical conditions depending on the vessel type. The intimal layer, in particular, is directly exposed to such hemodynamic conditions inducing shear stress, which in turn influence vascular physiology. 3D bioprinting techniques have addressed the structural limitations of the previous vascular models, by incorporating supporting cells such as smooth muscle cells, geometrical properties such as dilation, curvature, or branching, or mechanical stimulation such as shear stress and pulsatile pressure. This paper presents a review of the physiology of blood vessels along with the pathophysiology of the target diseases including atherosclerosis, thrombosis, aneurysms, and tumor angiogenesis. Additionally, it discusses recent advances in fabricatingin vitro3D vascular disease models utilizing bioprinting techniques, while addressing the current challenges and future perspectives for the potential clinical translation into therapeutic interventions.

Three-dimensional (3D) bio-derived materials are emerging as a promising approach to enhance wound healing therapies. These innovative materials can be tailored to meet the specific needs of various wound types and patients, facilitating the controlled release of therapeutic agents such as growth factors and antibiotics, which promote cell growth and tissue regeneration. Despite their potential, significant challenges remain in achieving optimal biocompatibility, ensuring structural integrity, and maintaining precise release mechanisms. Additionally, issues such as scalability, cost-effectiveness, and regulatory compliance pose substantial barriers to widespread use. However, recent advances in materials science and interdisciplinary research offer new opportunities to overcome these challenges. This review provides a comprehensive analysis of the current state of 3D bio-derived materials in biomedical applications, highlighting the types of materials available, their advantages and limitations, and the progress made in their design and development. It also outlines new directions for future research aimed at bridging the gap between scientific discoveries and their practical applications in injury healing strategies. The findings of this review underscore the significant potential of 3D bio-derived materials in revolutionizing wound healing and advancing personalized therapeutic approaches.

Thermoresponsive polymers have been extensively reported for their use in tissue engineering and drug delivery applications. They have a wide range of thermoresponsive and rheological properties controlled by their structural characteristics, such as composition and architecture. Here, the considerable potential of a PEG based, non-ionic triblock thermoresponsive copolymer, namely OEGMA30013-b-BuMA22-b-DEGMA12 as a bioink for 3D printing with cell encapsulation is identified. The rheological tests showed that the gel transition temperature is 8 °C with 35% w/w concentration in PBS. The printability and cytotoxicity of the thermoresponsive gel were characterised and compared with those of commercial thermoresponsive polymer Pluronic®F127 in detail. Specifically, the 35% w/w triblock copolymer presented great printability with a printing speed of 450 mm min-1 at 37 °C, and was less cytotoxic than F127 at both 20% and 30% w/w concentrations. A one-layer structure of human mesenchymal stem cell (hMSC) embedded triblock copolymer was successfully printed onto a glass slide at 37 °C. This provides an option to create a scaffold for stem cell culture and programming for further tissue engineering applications via direct printing of a cell-laden thermoresponsive polymer.

Zone II flexor digitorum profundus (FDP) tendon injuries are complex, and present significant challenges in hand surgery, due to the need to balance strength and flexibility during repair. Traditional suture techniques often lead to complications such as adhesions or tendon rupture, prompting the exploration of novel strategies to improve outcomes. This review investigates the use of flexor digitorum superficialis (FDS) tendon autografts to reinforce FDP repairs, alongside the integration of biomaterials to enhance mechanical strength without sacrificing FDS tissue. Key biomaterials, including collagen-polycaprolactone (PCL) composites, are evaluated for their biocompatibility, mechanical integrity, and controlled degradation properties. Collagen-PCL emerges as a leading candidate, offering the potential to reduce adhesions and promote tendon healing. Although nanomaterials such as nanofibers and nanoparticles show promise in preventing adhesions and supporting cellular proliferation, their application remains limited by manufacturing challenges. By combining advanced repair techniques with biomaterials like collagen-PCL, this approach aims to improve surgical outcomes and minimize complications. Future research will focus on validating these findings in biological models, assessing tendon healing through imaging, and comparing the cost-effectiveness of biomaterial-enhanced repairs with traditional methods. This review underscores the potential for biomaterial-based approaches to transform FDP tendon repair.

Regenerative dentistry aims to reinstate, fix, renew, and regrow tissues within the oral and craniofacial domain. Existing regenerative methods are based on insights into tissue biology or disease processes that lead to tissue degradation. However, achieving complete and functional Tissue regeneration remains a primary challenge in real-world medical scenarios.

The review focuses on the application of bioprinting techniques for rejuvenating intricate Oral and craniofacial tissues, such as craniofacial bone, periodontal ligament, cementum, dental pulp, temporomandibular joint cartilage, and whole teeth.

Bioprinting, a cutting-edge technology in regenerative dentistry, strives to create entirely new Functional tissues and organs. This approach merges principles from engineering and biology to produce three-dimensional biologically operational constructs containing bioactive substances, Living cells and cell clusters using automated bioprinters. The review summarizes the outcomes achieved through bioprinting techniques in both in vitro (laboratory experiments) and in vivo (Studies on living organisms) experiments.

The emergence of this innovative tissue engineering technology has yielded highly promising outcomes during the experimental stages.

These promising experimental results necessitate replication through human clinical trials to ascertain the viability of bioprinting techniques for mainstream clinical implementation in regenerative dentistry.

With prevalence of chronic kidney disease (CKD) in worldwide, the strategies to recover renal function via tissue regeneration could provide alternatives to kidney replacement therapies. However, due to relatively low reproducibility of renal basal cells and limited bioactivities of implanted biomaterials along with the high probability of substance-inducible inflammation and immunogenicity, kidney tissue regeneration could be challenging.

To exclude various side effects from cell transplantations, in this study, we have induced extracellular vesicles (EVs) incorporated cell-free hybrid PMEZ scaffolds.

Hybrid PMEZ scaffolds incorporating essential bioactive components, such as ricinoleic acid grafted Mg(OH)2 (M), extracellular matrix (E), and alpha lipoic acid-conjugated ZnO (Z) based on biodegradable porous PLGA (P) platform was successfully manufactured. Consecutively, for functional improvements, melatonin-modulated extracellular vesicles (mEVs), derived from the human umbilical cord MSCs in chemically defined media without serum impurities, were also loaded onto PMEZ scaffolds to construct the multiplexed PMEZ/mEV scaffold.

With functionalities of Mg(OH)2 and extracellular matrix-loaded PLGA scaffolds, the continuous nitric oxide-releasing property of modified ZnO and remarkably upregulated regenerative functionalities of mEVs showed significantly enhanced kidney regenerative activities. Based on these, the structural and functional restoration has been practically achieved in 5/6 nephrectomy mouse models that mimicked severe human CKD.

Our study has proved the combinatory bioactivities of the biodegradable PLGA-based multiplexed scaffold for kidney tissue regeneration in 5/6 nephrectomy mouse representing a severe CKD model. The optimal microenvironments for the morphogenetic formations of renal tissues and functional restorations have successfully achieved the combinatory bioactivities of remarkable components for PMEZ/mEV, which could be a promising therapeutic alternative for CKD treatment.

This study aims to characterize a three-dimensional-printed hydroxyapatite (HA)/polycaprolactone (PCL) scaffold and assess its biocompatibility both in vitro and in vivo.

A bionic, porous HA/PCL scaffold was fabricated using 3D printing, and its microstructure, porosity, hydrophilicity, and mechanical properties were evaluated through scanning electron microscopy and various assays. Bone marrow mesenchymal stem cells (BMSCs) and vascular endothelial progenitor cells (VEPCs) were co-cultured with the scaffold, and their proliferation and osteogenic differentiation were assessed using the Cell Counting Kit-8, ALP assays, and alizarin red staining. Osteogenic marker expression was analyzed via qRT-PCR. In vivo bone regeneration was evaluated through histological analysis of H&E and Masson's trichrome staining in a rat cranial defect model.

The average pore size of the scaffold was 462.00 ± 100.389 μm, with a porosity of 53%, a water absorption expansion rate of 5.10%, a contact angle of 94.55°, an elastic modulus of 53.82 MPa, and a compressive strength of 6.10 MPa. ALP activity and qRT-PCR analysis of osteogenic markers (BMP2, OCN, Runx2) showed significant upregulation in cells co-cultured with the scaffolds. In vivo experiments demonstrated enhanced bone regeneration and collagen deposition in the HA/PCL scaffold group.

The results suggest that the HA/PCL scaffold promotes osteogenic differentiation and bone regeneration, making it suitable for bone tissue engineering applications.

Fused Deposition Modeling (FDM) is a prominent additive manufacturing technique known for its ability to provide cost-effective and fast printing solutions. FDM enables the production of computer-aided 3D designs as solid objects at macro scales with high-precision alignment while sacrificing excellent surface smoothness compared to other 3D printing techniques such as SLA (Stereolithography) and SLS (Selective Laser Sintering). Electro-Spinning (ES) is another technique for producing soft-structured nonwoven micro-scale materials, such as nanofibers. However, compared to the FDM technique, it has limited accuracy and sensitivity regarding high-precision alignment. The need for high-precision alignment of micro-scaled soft structures during the printing process raises the question of whether FDM and ES techniques can be combined. Today, the printing technique with such capability is called Melt Electro Writing (MEW), and in practice, it refers to the basic working principle on which bio-printers are based. This paper aims to examine how these two techniques can be combined affordably. Comparatively, it presents output production processes, design components, parameters, and materials used in output production. It discusses the limitations and advantages of such a hybrid platform, specifically from the perspective of engineering design and its biomedical applications.

Mesenchymal stem cells (MSCs) have gained recognition as a highly versatile and promising cell source for repopulating bioengineered scaffolds due to their inherent capacity to differentiate into multiple cell types. However, MSC implantation techniques have often yielded inconsistent clinical results, underscoring the need for advanced approaches to enhance their therapeutic efficacy. Recent developments in three-dimensional (3D) bioengineered scaffolds have provided a significant breakthrough by closely mimicking the in vivo environment, addressing the limitations of traditional two-dimensional (2D) cell cultures. Among these, nanofibrous scaffolds have proven particularly effective, offering an optimal 3D framework, growth-permissive substrates, and the delivery of trophic factors crucial for MSC survival and regeneration. Furthermore, the selection of appropriate biomaterials can amplify the paracrine effects of MSCs, promoting both proliferation and targeted differentiation. The synergistic combination of MSCs with nanofibrous scaffolds has demonstrated remarkable potential in achieving repair, regeneration, and tissue-specific differentiation with enhanced safety and efficacy, paving the way for routine clinical applications. In this review, we examine the most recent studies (2013-2023) that explore the combined use of MSCs and nanofibrous scaffolds for differentiation into cardiogenic, epithelial, myogenic, tendon, and vascular cell lineages. Using PubMed, we identified and analyzed 275 relevant articles based on the search terms "Nanofibers", "Electrospinning", "Mesenchymal stem cells", and "Differentiation". This review highlights the critical advancements in the use of nanofibrous scaffolds as a platform for MSC differentiation and tissue regeneration. By summarizing key findings from the last decade, it provides valuable insights for researchers and clinicians aiming to optimize scaffold design, MSC integration, and translational applications. These insights could significantly influence future research directions and the development of more effective regenerative therapies.

Osteoporosis results from a disruption in skeletal homeostasis caused by an imbalance between bone resorption and bone formation. Conventional treatments, such as pharmaceutical drugs and hormone replacement therapy, often yield suboptimal results and are frequently associated with side effects. Recently, biomaterial-based approaches have gained attention as promising alternatives for managing osteoporosis. This review summarizes the current advancements in 3D-printed biomaterials designed for osteoporosis treatment. The benefits of biomaterial-based approaches compared to traditional systemic drug therapies are discussed. These 3D-printed materials can be broadly categorized based on their functionalities, including promoting osteogenesis, reducing inflammation, exhibiting antioxidant properties, and inhibiting osteoclast activity. 3D printing has the advantages of speed, precision, personalization, etc. It is able to satisfy the requirements of irregular geometry, differentiated composition, and multilayered structure of articular osteochondral scaffolds with boundary layer structure. The limitations of existing biomaterials are critically analyzed and future directions for biomaterial-based therapies are considered.

In this work, double-layer heterogeneous CA scaffolds were designed for alveolar bone defects. The outer layer featured high hardness and slow degradation, and large pores and rapid degradation characterized the inner layer. The CA scaffold morphology was akin to bone defects, and its direct implantation reduced the operation time. A higher concentration of CA resulted in smaller pores and slower degradation. CA can promote the formation of mineralized nodules and the expression of genes related to mineralization without inducing cytotoxic effects. It also promoted the expression of cellular inflammatory factors, potentially through the TLR4 pathway. In vivo studies confirmed that CA did not promote the aggregation of inflammatory cells or the expression of inflammatory factors. In conclusion, the scaffold's characteristics of high surface hardness and slow degradation were beneficial for surface osteogenesis and maintaining the defect's shape and osteogenic space. Conversely, rapid internal degradation favors the formation of bone tissue.

There is a pressing need for new cell-laden, printable bioinks to mimic stiffer tissues such as cartilage, fibrotic tissue and bone. PEGDA monomers are bioinks that crosslink with light to form a viscoelastic solid, however, they lack cell adhesion properties. Here, we utilized a hybrid bioink by combining self-assembled peptide nanofibers with PEGDA for 3D printing lumens. Adult human dermal fibroblast (aHDF) cells were first seeded in peptide-laden in 2D and 3D layers and cell behavior were studied. The cell's morphology remained spheres when they were infused in the 3D hydrogel and highly aligned with 2D overlay hydrogels. HDF cells did not adhere to unmodified PEGDA lumens, however, they successfully attached and proliferated on PEGDA/peptide lumens. Moreover, HDF cells seeded on the hybrid PEGDA/peptide lumens displayed a distinct spread F-actin morphology. The results showcase the potential of peptide hydrogels in facilitating interaction of anchorage dependent cells with PEGDA structures.

Organoids, with their capacity to mimic the structures and functions of human organs, have gained significant attention for simulating human pathophysiology and have been extensively investigated in the recent past. Additionally, 3D bioprinting, as an emerging bio-additive manufacturing technology, offers the potential for constructing heterogeneous cellular microenvironments, thereby promoting advancements in organoid research. In this review, the latest developments in 3D bioprinting technologies aimed at enhancing organoid engineering are introduced. The commonly used bioprinting methods and materials for organoids, with a particular emphasis on the potential advantages of combining 3D bioprinting with organoids are summarized. These advantages include achieving high cell concentrations to form large cellular aggregates, precise deposition of building blocks to create organoids with complex structures and functions, and automation and high throughput to ensure reproducibility and standardization in organoid culture. Furthermore, this review provides an overview of relevant studies from recent years and discusses the current limitations and prospects for future development.

Regenerative medicine refers to medical research focusing on repairing, replacing, or regenerating damaged or diseased tissues or organs. Cardiovascular disease (CVDs) is a significant health issue globally and is the leading cause of death in many countries. According to the Centers for Disease Control and Prevention (CDC), one person dies every 34 seconds in the United States from cardiovascular diseases, and according to a World Health Organization (WHO) report, cardiovascular diseases are the leading cause of death globally, taking an estimated 17.9 million lives each year. Many conventional treatments are available using different drugs for cardiovascular diseases, but these treatments are inadequate. Stem cells and nanotechnology are promising research areas for regenerative medicine treating CVDs. Regenerative medicines are a revolutionary strategy for advancing and successfully treating various diseases, intending to control cardiovascular disorders. This review is a comprehensive study of different treatment methods for cardiovascular diseases using different types of biomaterials as regenerative medicines, the importance of different stem cells in therapeutics, the expanded role of nanotechnology in treatment, the administration of several types of stem cells, their tracking, imaging, and the final observation of clinical trials on many different levels as well as it aims to keep readers up to pace on emerging therapeutic applications of some specific organs and disorders that may improve from regenerative medicine shortly.

Drug delivery systems (DDSs) are increasingly important in ensuring drug safety and enhancing therapeutic efficacy. Micro/nano-technology has been utilized to develop DDSs for achieving high stability, bioavailability, and drug efficiency, as well as targeted delivery; meanwhile, 3D printing technology has made it possible to tailor DDSs with diverse components and intricate structures. This review presents the latest research progress integrating 3D printing technology and micro/nano-technology for developing novel DDSs. The technological fundamentals of 3D printing technology supporting the development of DDSs are presented, mainly from the perspective of different 3D printing mechanisms. Distinct types of DDSs leveraging 3D printing and micro/nano-technology are analyzed deeply, featuring micro/nanoscale materials and structures to enrich functionalities and improve effectiveness. Finally, we will discuss the future directions of 3D-printed DDSs integrated with micro/nano-technology, focusing on technological innovation and clinical application. This review will support interdisciplinary research efforts to advance drug delivery technology.

Drawing inspiration from nature, soft materials are at the core of a transformation toward adaptive and responsive engineered systems, capable of conquering demanding terrain and safe when interacting with biological life. Despite recent advances in 3D printing of soft materials, researchers are still far from being able to print complex soft systems where a multitude of different components need to work together symbiotically. Closing this gap necessitates a platform that unites diverse materials into one synergetic process. Here, a multi-material printing system is presented, combining gelatin-based hydrogels with a new biodegradable support material. This organic ink maintains up to 60° overhang and is printable over gaps to structurally support the main biogel body, while triggered dissolution enables its selective removal and the formation of internal cavities. Therefore, the creation of vascular networks, tunable scaffolds, and embedded sensors within a single printing process becomes feasible. Furthermore, a perforation-resistant, joint-like vacuum actuator (VAc) is designed and 3D printed, capable of bending to angles up to 60° at fast response times down to 0.23 s. Combining these approaches in an efficient, streamlined fabrication process with biodegradable materials will unlock new sustainability dimensions for complex and durable soft systems.

The current gold-standard approach for addressing bone defects in load-bearing applications sees the use of either autographs or allographs. These solutions, however, have limitations as autographs and allographs carry the risk of additional trauma, the threat of disease transmission, and potential donor rejection. An attractive candidate for overcoming the challenges associated with the use of autographs and allographs is a 3D porous scaffold displaying the needed mechanical competency for use in load-bearing applications that can stimulate bone tissue regeneration and provide antibacterial capabilities. To date, no reports document a 3D porous scaffold that fully meets the criteria specified above. In this work, we show how the use of fused filament fabrication (FFF) 3D printing technology in combination with a bimodal distribution of Ag-doped bioactive glass-ceramic (Ag-BG) micro-sized particles can successfully deliver porous 3D scaffolds with attractive and reliable mechanical performance characteristics capable of stimulating bone tissue regeneration and the ability to provide inherent antibacterial properties. To characterize the reliability of the mechanical performance of the FFF-printed Ag-BG scaffolds, Weibull statistics were evaluated for both the compressive (N = 25; m = 13.6 ± 0.9) and flexural (N = 25; m = 7.3 ± 0.7) strengths. Methicillin-resistant Staphylococcus aureus (MRSA) was used both in planktonic and biofilm forms to highlight the advanced antibacterial characteristics of the FFF-printed Ag-BG scaffolds. Biological performance was evaluated in vitro through indirect exposure to human marrow stromal cells (hMSCs), where the FFF-printed Ag-BG scaffolds were found to provide an attractive environment for cell infiltration and mineralization. Our work demonstrates how fused filament fabrication technology can be used with bioactive and antibacterial materials such as Ag-BG to deliver mechanically competent porous 3D scaffolds capable of stimulating bone tissue regeneration while simultaneously providing antibacterial performance capabilities.

Critical-sized mandibular bone defects, arising from, for example, resections after tumor surgeries, are currently treated with autogenous bone grafts. This treatment is considered very invasive and is associated with limitations such as morbidity and graft resorption. Tissue engineering approaches propose to use 3D scaffolds that combine structural features, biomaterial properties, cells, and biomolecules to create biomimetic constructs. However, mimicking the complex anatomy and composition of the mandible poses a challenge in scaffold design. In our study, we evaluated the dual effect of complex pore geometry and material composition on the osteogenic potential of 3D printed scaffolds. The scaffolds were made of polycaprolactone (PCL) alone (TCP0), or with a high concentration of β-tricalcium phosphate (β-TCP) up to 40% w/w (TCP40), with two complex pore geometries, namely a star- (S) and a diamond-like (D) shape. Scanning electron microscopy and microcomputed tomography images confirmed high fidelity during the printing process. The D-scaffolds displayed higher compressive moduli than the corresponding S-scaffolds. TCP40 scaffolds in simulated body fluid showed deposition of minerals on the surface after 28 days. Subsequently, we assessed the differentiation of seeded bone marrow-derived human mesenchymal stromal cells (hMSCs) over 28 days. The early expression of RUNX2 in the cell nuclei confirmed the commitment toward an osteogenic phenotype. Moreover, alkaline phosphatase (ALP) activity and collagen deposition displayed an increasing trend in the D-scaffolds. Collagen type I was mainly present in the deposited extracellular matrix (ECM), confirming deposition of bone matrix. Finally, Alizarin Red staining showed successful mineralization on all the TCP40 samples, with higher values for the S-shaped scaffolds. Taken together, our study demonstrated that the complex pore architectures of scaffolds comprised TCP40 stimulated osteogenic differentiation and mineralization of hMSCs in vitro. Future research will aim to validate these findings in vivo.

Bone tissue engineering is a promising approach to address the increasing need for bone repair. Scaffolds play a crucial role in providing the structural framework for cell growth and differentiation. 3D printing offers precise control over scaffold design and fabrication. Polymers and inorganic compounds such as magnetic nanoparticles (MNPs) are used to create biocompatible and functional scaffolds. MNPs enhance mechanical properties, facilitate drug delivery, and enable the real-time monitoring of bone regeneration. This review highlights the potential of polymer-based 3D-printed magnetic scaffolds in advancing bone regenerative medicine.

The field of biomedical engineering continually seeks innovative technologies to address complex healthcare challenges, ranging from tissue regeneration to drug delivery and biosensing. Plant skeletons offer promising opportunities for these applications due to their unique hierarchical structures, desirable porosity, inherent biocompatibility, and adjustable mechanical properties. This review comprehensively discusses chemical principles underlying the utilization of plant-based scaffolds in biomedical engineering. Highlighting their structural integrity, tunable properties, and possibility of chemical modification, the review explores diverse preparation strategies to tailor plant skeleton properties for bone, neural, cardiovascular, skeletal muscle, and tendon tissue engineering. Such applications stem from the cellulosic three-dimensional structure of different parts of plants, which can mimic the complexity of native tissues and extracellular matrices, providing an ideal environment for cell adhesion, proliferation, and differentiation. We also discuss the application of plant skeletons as carriers for drug delivery due to their structural diversity and versatility in encapsulating and releasing therapeutic agents with controlled kinetics. Furthermore, we present the emerging role played by plant-derived materials in biosensor development for diagnostic and monitoring purposes. Challenges and future directions in the field are also discussed, offering insights into the opportunities for future translation of sustainable plant-based technologies to address critical healthcare needs.

Increasing bone diseases and anomalies significantly challenge bone regeneration, necessitating the development of innovative implantable devices for effective healing. This study explores the potential of 3D-printed calcium phosphate (CaP) scaffolds functionalized with natural medicine to address this issue. Specifically, quercetin and vitamin D3 (QVD) encapsulated solid lipid nanoparticles (QVD-SLNs) are incorporated into the scaffold to enhance bone regeneration. The melt emulsification method is utilized to achieve high drug encapsulation efficiency (~98%) and controlled biphasic release kinetics. The process-structure-property performance of these systems allows more controlled release while maintaining healthy cell-material interactions. The functionalized scaffolds show ~1.3- and ~-1.6-fold increase in osteoblast cell proliferation and differentiation, respectively, as compared with the control. The treated scaffold demonstrates a reduction in osteoclastic activity as compared with the control. The QVD-SLN-loaded scaffolds show ~4.2-fold in vitro chemopreventive potential against osteosarcoma cells. Bacterial assessment with both Staphylococcus aureus and Pseudomonas aeruginosa shows a significant reduction in bacterial colony growth over the treated scaffold. These findings summarize that the release of QVD-SLNs through a 3D-printed CaP scaffold can treat various bone-related disorders for low or non-load-bearing applications.

Wound healing comprises four overlapping stages involving complex biochemical and cellular processes. Any lapse in this procedure causes irregular healing, which generates clinical and financial burdens for the health system. Personalized treatment is preferred to overcome the limitations of classical as well as modern methods of wound healing. This review discusses recently developed 3D printing models for personalized treatment with varying degrees of success. It is an effective approach for treating wounds by developing custom dressings tailored to the patient's needs and reducing incidents of infections. Additionally, incorporating natural or synthetic polymers can further enhance their effectiveness. Macromolecular polymers, laminin, cellulose, collagen, gelatin, etc. that make up the bulk of 3D printable bio-inks, have been essential in diverse 3D bioprinting technologies throughout the layered 3D manufacturing processes. The polymers need to be tailored for the specific requirements of printing and effector functions in cancer treatment, dental & oral care, biosensors, and muscle repair. We have explored how 3D printing can be utilized to fasten the process of wound healing at each of the four stages. The benefits as well as the future prospects are also discussed in this article.

The field of wound healing faces significant challenges, particularly in the treatment of chronic wounds, which often result in prolonged healing times and complications. Recent advancements in 3D printing technology have provided innovative solutions to these challenges, offering tailored and precise approaches to wound care. This review highlights the role of 3D printing in enhancing wound healing, focusing on its application in creating biocompatible scaffolds, custom wound dressings, and drug delivery systems. By mimicking the extracellular matrix (ECM) and facilitating cell proliferation, 3D-printed biomaterials have the potential to significantly accelerate the healing process. In addition, 3D bioprinting enables the production of functional skin substitutes that can be customized for individual patients. Despite the promise of these technologies, several challenges remain, including the need for improved vascularization, cost concerns, and regulatory hurdles. The future of wound healing lies in the continued integration of 3D printing with emerging technologies such as 4D printing and bioelectronics, providing opportunities for personalized and on-demand therapies. This review explores the current state of 3D printing in wound care, its challenges, and the future potential of these innovative technologies.

Bone implantation is one of the recognized and effective means of treating bone defects, but osteoporosis and bone tumor-related bone abnormalities have a series of problems such as susceptibility to infection, difficulty in healing, and poor therapeutic effect, which poses a great challenge to clinical medicine. Three-dimensional things may be printed using 3D printing. Researchers can feed materials through the printer layer by layer to create the desired shape for a 3D structure. It is widely employed in the healing of bone defects, and it is an improved form of additive manufacturing technology with prospective future applications. This review's objective is to provide an overview of the findings reports pertaining to 3D printing biopolymers in recent years, provide an overview of biopolymer materials and their composites with black phosphorus for 3D printing bone implants, and the characterization methods of composite materials are also summarized. In addition, summarizes 3D printing methods based on ink printing and laser printing, pointing out their special features and advantages, and provide a combination strategy of photothermal therapy and bone regeneration materials for black phosphorus-based materials. Finally, the associations between bone implant materials and immune cells, the bio-environment, as well as the 3D printing bone implants prospects are outlined.

In order to solve the loosening problem caused by stress shielding of femoral stem prostheses in clinical practice, an optimization design method of a personalized porous titanium alloy femoral stem is proposed. According to the stress characteristics of the femur, the porous unit cell structures (TO-C, TO-T, TO-B) under three different loads of compression, torsion, and bending were designed by topology optimization. The mechanical properties and permeability of different structures were studied. Combined with the porous structure optimization, a personalized radial gradient porous titanium alloy femoral stem was designed and manufactured by selective laser melting (SLM) technology. The results show that the TO-B structure has the best comprehensive performance among the three topologically optimized porous types, which is suitable for the porous filling structure of the femoral stem, and the SLM-formed porous femoral stem has good quality. The feasibility of the personalized design and manufacture of porous titanium alloy implants is verified, which can provide a theoretical basis for the optimal design of implants in different parts.

Inducing osteogenic differentiation in vitro is useful for the identification and development of bone regeneration therapies as well as modelling bone disorders. To couple in vitro models with high throughput screening techniques retains the assay's relevance in research while increasing its therapeutic impact. Miniaturizing, automating and/or digitalizing in vitro assays will reduce the required quantity of cells, biologic stimulants, culture/output assay reagents, time and cost. This review highlights the design and workflow considerations for creating a high throughput screen-compatible model of osteogenesis, comparing and contrasting osteogenic cell type, assay fabrication and culture methodology, osteogenic induction approach and repurposing existing output techniques.

This systematic review aims to assess and summarize the current landscape in exoskeletons and orthotic solutions developed for upper limb medical assistance, which are partly or fully produced using 3-dimensional printing technologies and contain at least the elbow or the shoulder joints. The initial search was conducted on Web of Science, PubMed, and IEEEXplore, resulting in 92 papers, which were reduced to 72 after removal of duplicates. From the application of the inclusion and exclusion criteria and selection questionnaire, 33 papers were included in the review, being divided according to the analyzed joints. The analysis of the selected papers allowed for the identification of different solutions that vary in terms of their target application, actuation type, 3-dimensional printing techniques, and material selection, among others. The results show that there has been far more research on the elbow joint than on the shoulder joint, which can be explained by the relative complexity of the latter. Moreover, the findings of this study also indicate that there is still a gap between the research conducted on these devices and their practical use in real-world conditions. Based on current trends, it is anticipated that the future of 3-dimensional printed exoskeletons will revolve around the use of flexible and high-performance materials, coupled with actuated devices. These advances have the potential to replace the conventional fabrication methods of exoskeletons with technologies based on additive manufacturing.

There are currently no targeted delivery systems to satisfactorily treat bone-related disorders. Many clinical drugs consisting of small organic molecules have a short circulation half-life and do not effectively reach the diseased tissue site. This coupled with repeatedly high dose usage that leads to severe side effects. With the advance in nanotechnology, drugs contained within a nano-delivery device or drugs aggregated into nanoparticles (nano-drugs) have shown promises in targeted drug delivery. The ability to design nanoparticles to target bone has attracted many researchers to develop new systems for treating bone related diseases and even repurposing current drug therapies. In this review, we shall summarise the latest progress in this area and present a perspective for future development in the field. We will focus on calcium-based nanoparticle systems that modulate calcium metabolism and consequently, the bone microenvironment to inhibit disease progression (including cancer). We shall also review the bone affinity drug family, bisphosphonates, as both a nano-drug and nano-delivery system for bone targeted therapy. The ability to target and release the drug in a controlled manner at the disease site represents a promising safe therapy to treat bone diseases in the future.

Injuries to fibrous connective tissues have very little capacity for self-renewal and exhibit poor healing after injury. Phenotypic shifts in macrophages play a vital role in mediating the healing response, creating an opportunity to design immunomodulatory biomaterials which control macrophage polarization and promote regeneration. In this study, electrospun poly(-caprolactone) fibers with increasing surface roughness (SR) were produced by increasing relative humidity and inducing vapor-induced phase separation during the electrospinning process. The impact of surface roughness on macrophage phenotype was assessed using human monocyte-derived macrophages in vitro and in vivo using B6.Cg-Tg(Csf1r-EGFP)1Hume/J (MacGreen) mice. In vitro experiments showed that macrophages cultured on mesh with increasing SR exhibited decreased release of both pro- and anti-inflammatory cytokines potentially driven by increased protein adsorption and biophysical impacts on the cells. Further, increasing SR led to an increase in the expression of the pro-regenerative cell surface marker CD206 relative to the pro-inflammatory marker CD80. Mesh with increasing SR were implanted subcutaneously in MacGreen mice, again showing an increase in the ratio of cells expressing CD206 to those expressing CD80 visualized by immunofluorescence. SR on implanted biomaterials is sufficient to drive macrophage polarization, demonstrating a simple feature to include in biomaterial design to control innate immunity.

Assisted Reproductive Technologies (ARTs) have been validated in human and animal to solve reproductive problems such as infertility, aging, genetic selection/amplification and diseases. The persistent gap in ART biomedical applications lies in recapitulating the early stage of ovarian folliculogenesis, thus providing protocols to drive the large reserve of immature follicles towards the gonadotropin-dependent phase. Tissue engineering is becoming a concrete solution to potentially recapitulate ovarian structure, mostly relying on the use of autologous early follicles on natural or synthetic scaffolds. Based on these premises, the present study has been designed to validate the use of the ovarian bioinspired patterned electrospun fibrous scaffolds fabricated with poly(ε-caprolactone) (PCL) for multiple preantral (PA) follicle development.

PA follicles isolated from lamb ovaries were cultured on PCL scaffold adopting a validated single-follicle protocol (Ctrl) or simulating a multiple-follicle condition by reproducing an artificial ovary engrafted with 5 or 10 PA (AO5PA and AO10PA). The incubations were protracted for 14 and 18 days before assessing scaffold-based microenvironment suitability to assist in vitro folliculogenesis (ivF) and oogenesis at morphological and functional level.

The ivF outcomes demonstrated that PCL-scaffolds generate an appropriate biomimetic ovarian microenvironment supporting the transition of multiple PA follicles towards early antral (EA) stage by supporting follicle growth and steroidogenic activation. PCL-multiple bioengineering ivF (AO10PA) performed in long term generated, in addition, the greatest percentage of highly specialized gametes by enhancing meiotic competence, large chromatin remodeling and parthenogenetic developmental competence.

The study showcased the proof of concept for a next-generation ART use of PCL-patterned scaffold aimed to generate transplantable artificial ovary engrafted with autologous early-stage follicles or to advance ivF technologies holding a 3D bioinspired matrix promoting a physiological long-term multiple PA follicle protocol.

Bone tissue defects present a major challenge in orthopedic surgery. Bone tissue engineering using multiple versatile bioactive materials is a potential strategy for bone-defect repair and regeneration. Due to their unique physicochemical and mechanical properties, biofunctional materials can enhance cellular adhesion, proliferation, and osteogenic differentiation, thereby supporting and stimulating the formation of new bone tissue. 3D bioprinting and physical stimuli-responsive strategies have been employed in various studies on bone regeneration for the fabrication of desired multifunctional biomaterials with integrated bone tissue repair and regeneration properties. In this review, biomaterials applied to bone tissue engineering, emerging 3D bioprinting techniques, and physical stimuli-responsive strategies for the rational manufacturing of novel biomaterials with bone therapeutic and regenerative functions are summarized. Furthermore, the impact of biomaterials on the osteogenic differentiation of stem cells and the potential pathways associated with biomaterial-induced osteogenesis are discussed.

Tissue engineering is a multidisciplinary field that merges engineering, material science, and medical biology in order to develop biological alternatives for repairing, replacing, maintaining, or boosting the functionality of tissues and organs. The ultimate goal of tissue engineering is to create biological alternatives for repairing, replacing, maintaining, or enhancing the functionality of tissues and organs. However, the current landscape of tissue engineering techniques presents several challenges, including a lack of suitable biomaterials, inadequate cell proliferation, limited methodologies for replicating desired physiological structures, and the unstable and insufficient production of growth factors, which are essential for facilitating cell communication and the appropriate cellular responses. Despite these challenges, there has been significant progress made in tissue engineering techniques in recent years. Nanoparticles hold a major role within the realm of nanotechnology due to their unique qualities that change with size. These particles, which provide potential solutions to the issues that are met in tissue engineering, have helped propel nanotechnology to its current state of prominence. Despite substantial breakthroughs in the utilization of nanoparticles over the past two decades, the full range of their potential in addressing the difficulties within tissue engineering remains largely untapped. This is due to the fact that these advancements have occurred in relatively isolated pockets. In the realm of tissue engineering, the purpose of this research is to conduct an in-depth investigation of the several ways in which various types of nanoparticles might be put to use. In addition to this, it sheds light on the challenges that need to be conquered in order to unlock the maximum potential of nanotechnology in this area.

Spinal cord injury (SCI) is an important factor in sensory and motor disorders that affects thousands of people every year. Currently, despite successes in basic science and clinical research, there are few effective methods in the treatment of chronic and acute spinal cord injuries. In the last decade, the use of 3D printed scaffolds in the treatment of SCI had satisfactory and promising results. By providing a microenvironment around the injury site and in combination with growth factors or cells, 3D printed scaffolds help in axon regeneration as well as neural recovery after SCI. Here, we provide an overview of tissue engineering, 3D printing scaffolds, the different polymers used and their characterization methods. This review highlights the recent encouraging applications of 3D printing scaffolds in developing the novel SCI therapy.

Biomaterials are defined as "engineered materials" and include a range of natural and synthetic products, designed for their introduction into and interaction with living tissues. Biomaterials are considered prominent tools in regenerative medicine that support the restoration of tissue defects and retain physiologic functionality. Although commonly used in the medical field, these constructs are inherently foreign toward the host and induce an immune response at the material-tissue interface, defined as the foreign body response (FBR). A strong connection between the foreign body response and tissue regeneration is suggested, in which an appropriate amount of immune response and macrophage polarization is necessary to trigger autologous tissue formation. Recent developments in this field have led to the characterization of immunomodulatory traits that optimizes bioactivity, the integration of biomaterials and determines the fate of tissue regeneration. This review addresses a variety of aspects that are involved in steering the inflammatory response, including immune cell interactions, physical characteristics, biochemical cues, and metabolomics. Harnessing the advancing knowledge of the FBR allows for the optimization of biomaterial-based implants, aiming to prevent damage of the implant, improve natural regeneration, and provide the tools for an efficient and successful in vivo implantation.

A direct and comprehensive comparative study on different 3D printing modalities was performed. We employed two representative 3D printing modalities, laser- and extrusion-based, which are currently used to produce patient-specific medical implants for clinical translation, to assess how these two different 3D printing modalities affect printing outcomes. The same solid and porous constructs were created from the same biomaterial, a blend of 96% poly-ε-caprolactone (PCL) and 4% hydroxyapatite (HA), using two different 3D printing modalities. Constructs were analyzed to assess their printing characteristics, including morphological, mechanical, and biological properties. We also performed an in vitro accelerated degradation study to compare their degradation behaviors. Despite the same input material, the 3D constructs created from different 3D printing modalities showed distinct differences in morphology, surface roughness and internal void fraction, which resulted in different mechanical properties and cell responses. In addition, the constructs exhibited different degradation rates depending on the 3D printing modalities. Given that each 3D printing modality has inherent characteristics that impact printing outcomes and ultimately implant performance, understanding the characteristics is crucial in selecting the 3D printing modality to create reliable biomedical implants.