Tissue Engineering Strategies Research Articles

Activating UCHL1 through the CRISPR activation system promotes cartilage differentiation mediated by HIF-1α/SOX9.

Developing strategies to enhance cartilage differentiation in mesenchymal stem cells and preserve the extracellular matrix is crucial for successful cartilage tissue reconstruction. Hypoxia-inducible factor-1α (HIF-1α) plays a pivotal role in maintaining the extracellular matrix and chondrocyte phenotype, thus serving as a key regulator in chondral tissue engineering strategies. Recent studies have shown that Ubiquitin C-terminal hydrolase L1 (UCHL1) is involved in the deubiquitylation of HIF-1α. However, the regulatory role of UCHL1 in chondrogenic differentiation has not been investigated. In the present study, we initially validated the promotive effect of UCHL1 expression on chondrogenesis in adipose-derived stem cells (ADSCs). Subsequently, a hybrid baculovirus system was designed and employed to utilize three CRISPR activation (CRISPRa) systems, employing dead Cas9 (dCas9) from three distinct bacterial sources to target UCHL1. Then UCHL1 and HIF-1α inhibitor and siRNA targeting SRY-box transcription factor 9 (SOX9) were used to block UCHL1, HIF-1α and SOX9, respectively. Cartilage differentiation and chondrogenesis were measured by qRT-PCR, immunofluorescence and histological staining. We observed that the CRISPRa system derived from Staphylococcus aureus exhibited superior efficiency in activating UCHL1 compared to the commonly used the CRISPRa system derived from Streptococcus pyogenes. Furthermore, the duration of activation was extended by utilizing the Cre/loxP-based hybrid baculovirus. Moreover, our findings show that UCHL1 enhances SOX9 expression by regulating the stability and localization of HIF-1α, which promotes cartilage production in ADSCs. These findings suggest that activating UCHL1 using the CRISPRa system holds significant potential for applications in cartilage regeneration.

Osteogenic differentiation of bone mesenchymal stem cells on linearly aligned triangular micropatterns.

Mesenchymal stem cells (MSCs) hold promise for regenerative medicine, particularly for bone tissue engineering. However, directing MSC differentiation towards specific lineages, such as osteogenic, while minimizing undesired phenotypes remains a challenge. Here, we investigate the influence of micropatterns on the behavior and lineage commitment of rat bone marrow-derived MSCs (rBMSCs), focusing on osteogenic differentiation. Linearly aligned triangular micropatterns (TPs) and circular micropatterns (CPs) coated with fibronectin were fabricated to study their effects on rBMSC morphology and differentiation and the underlying mechanobiological mechanisms. TPs, especially TP15 (15 μm), induced the cell elongation and thinning, while CPs also promoted the cell stretching, as evidenced by the decreased circularity and increased aspect ratio. TP15 significantly promoted osteogenic differentiation, with increased expression of osteogenic genes (Runx2, Spp1, Alpl, Bglap, Col1a1) and decreased expression of adipogenic genes (Pparg, Cebpa, Fabp4). Conversely, CPs inhibited both osteogenic and adipogenic differentiation. Mechanistically, TP15 increased Piezo1 activity, cytoskeletal remodeling including the aggregates of F-actin and myosin filaments at the cell periphery, YAP1 nuclear translocation, and integrin upregulation. Piezo1 inhibition suppressed the osteogenic genes expression, myosin remodeling, and YAP1 nuclear translocation, indicating Piezo1-mediated the mechanotransduction in rBMSCs on TPs. TP15 also induced osteogenic differentiation of BMSCs from aging rats, with upregulated Piezo1 and nuclear translocation of YAP1. Therefore, triangular micropatterns, particularly TP15, promote osteogenesis and inhibit adipogenesis of rBMSCs through Piezo1-mediated myosin and YAP1 pathways. Our study provides novel insights into the mechanobiological mechanisms governing MSC behaviors on micropatterns, offering new strategies for tissue engineering and regenerative medicine.

Recent advances in artificial intelligent strategies for tissue engineering and regenerative medicine.

Tissue engineering and regenerative medicine (TERM) aim to repair or replace damaged or lost tissues or organs due to accidents, diseases, or aging, by applying different sciences. For this purpose, an essential part of TERM is the designing, manufacturing, and evaluating of scaffolds, cells, tissues, and organs. Artificial intelligence (AI) or the intelligence of machines or software can be effective in all areas where computers play a role. The "artificial intelligence," "machine learning," "tissue engineering," "clinical evaluation," and "scaffold" keywords used for searching in various databases and articles published from 2000 to 2024 were evaluated. The combination of tissue engineering and AI has created a new generation of technological advancement in the biomedical industry. Experience in TERM has been refined using advanced design and manufacturing techniques. Advances in AI, particularly deep learning, offer an opportunity to improve scientific understanding and clinical outcomes in TERM. The findings of this research show the high potential of AI, machine learning, and robots in the selection, design, and fabrication of scaffolds, cells, tissues, or organs, and their analysis, characterization, and evaluation after their implantation. AI can be a tool to accelerate the introduction of tissue engineering products to the bedside. The capabilities of artificial intelligence (AI) can be used in different ways in all the different stages of TERM and not only solve the existing limitations, but also accelerate the processes, increase efficiency and precision, reduce costs, and complications after transplantation. ML predicts which technologies have the most efficient and easiest path to enter the market and clinic. The use of AI along with these imaging techniques can lead to the improvement of diagnostic information, the reduction of operator errors when reading images, and the improvement of image analysis (such as classification, localization, regression, and segmentation).

Supramolecular Composite Hydrogel Loaded with CaF2 Nanoparticles Promotes the Recovery of Periodontitis Bone Resorption.

Treatments to reduce periodontal inflammation and rescue periodontitis bone resorption have been of interest to researchers. Bone tissue engineering materials have been gradually used in the treatment of bone defects, but periodontal bone tissue regeneration still faces challenges. Considering the biocompatibility factor, constructing bionic scaffolds with natural extracellular matrix properties is an ideal therapeutic pathway. Based on the pathological mechanism of periodontitis, in this study, short peptide and nanometer inorganic particles were comingled to construct NapKFF-nano CaF2 supramolecular composite hydrogels with different ratios. Material characterization experiments confirmed that the composite hydrogel had suitable mechanical properties and a three-dimensional structure that can function in the resorption region of the alveolar bone and provide spaces for cell proliferation and adhesion. The release of low concentrations of fluoride and calcium ions has been shown to have positive biological effects in both in vivo and in vitro experiments. Vitro experiments confirmed that the composite hydrogel had good biocompatibility and promoted osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Microbiological experiments confirmed that the composite hydrogel inhibited the activity of periodontal pathogenic bacteria. In animal studies, composite hydrogel applied to periodontitis rats in vivo can effectively repair alveolar bone resorption. This composite hydrogel has a simple preparation method and is inexpensive to produce, yet it has antibacterial and osteogenesis-promoting incremental effects, which makes it well suited for the treatment of periodontitis bone resorption, providing a new strategy for periodontal bone tissue engineering.

Simultaneous electro-dynamic stimulation accelerates maturation of engineered cardiac tissues generated by human iPS cells

Electrical and dynamic stimulation are commonly employed to enhance the maturation of engineered cardiac tissue (ECT) derived from human induced pluripotent stem cells (iPSCs), reflecting the physiological environment of the heart. While electrical stimulation mimics natural bioelectrical signals and dynamic stimulation replicates mechanical forces, the combined effects of these stimuli on ECT maturation have not been thoroughly explored. We hypothesized that simultaneous electro-dynamic stimulation would enhance ECT maturation and function more effectively than either stimulus alone. Human iPSC-derived cardiovascular cells were co-cultured with Collagen I and Matrigel for 2 weeks, followed by a comparative analysis of four groups: no stimulation, dynamic stimulation, electrical stimulation, and simultaneous electro-dynamic stimulation. The functionality of ECTs was assessed by measuring contractile capacity and calcium indicators, and histological assessments examined structural maturation. Our results demonstrated that simultaneous electro-dynamic stimulation significantly increased the CM component, elevated TNNT2 mRNA expression levels, and enhanced calcium transient capacity. Additionally, ECTs subjected to simultaneous stimulation exhibited a positive force-frequency relationship in contractility and an elevation in peak calcium flux, indicative of advanced tissue maturation. Moreover, simultaneous stimulation promoted vascular network formation within the ECTs, suggesting improved structural organization. These findings underscore the importance of simultaneous stimulation for developing effective cardiac tissue engineering strategies.

Enhancement of Bone Repair in Diabetic Rats with Metformin-Modified Silicified Collagen Scaffolds.

Regenerating bone defects in diabetic rats presents a significant challenge due to the detrimental effects of reactive oxygen species and impaired autophagy on bone healing. To address these issues, a metformin-modified biomimetic silicified collagen scaffold is developed utilizing the principles of biomimetic silicification. In vitro and in vivo experiments demonstrated that the scaffold enhanced bone tissue regeneration within the diabetic microenvironment through the release of dual bio-factors. Further analysis reveals a potential therapeutic mechanism whereby these dual bio-factors synergistically promoted osteogenesis in areas of diabetic bone defects by improving mitochondrial autophagy and maintaining redox balance. The present study provides critical insights into the advancement of tissue engineering strategies aimed at bone regeneration in diabetic patients. The study also sheds light on the underlying biological mechanisms.

3D chitosan/hydroxyapatite scaffolds containing mesoporous SiO2-HA particles: A new step to healing bone defects

Biocompatible scaffolds with high mechanical strengths that contain biodegradable components could boost bone regeneration compared with nondegradable bone repair materials. In this study, porous chitosan (CS)/hydroxyapatite (HA) scaffolds containing mesoporous SiO2-HA particles were fabricated through the freeze-drying process. According to field emission scanning electron microscopy (FESEM) results, combining mesoporous SiO2-HA particles in CS/HA scaffolds led to a uniform porous structure. It decreased pore sizes from 320 ± 1.1 μm to 145 ± 1.4 μm. Moreover, the compressive strength value of this scaffold was 25 ± 1.2 MPa. The in-vitro approaches exhibited good sarcoma osteogenic cell line (SAOS-2) adhesion, spreading, and proliferation, indicating that the scaffolds provided a suitable environment for cell cultivation. Also, in-vivo analyses in implanted defect sites of rats proved that the CS/HA/mesoporous SiO2-HA scaffolds could promote bone regeneration via enhancing osteoconduction and meliorating the expression of osteogenesis gene to 19.31 (about 5-fold higher compared to the control group) by exposing them to the bone-like precursors. Further, this scaffold's new bone formation percentage was equal to 90 % after 21 days post-surgery. Therefore, incorporating mesoporous SiO2-HA particles into CS/HA scaffolds can suggest a new future tissue engineering and regeneration strategy.

Imparting of Nearly Superparamagnetic Properties to Cryogel Scaffolds With Mesoporous MNPs for Magneto-Sensitive Tissue Engineering Strategies.

This work reports the assembly of mesoporous iron oxide nanoparticles (meso-MNPs) with cryogel scaffolds composed of chitosan and gelatin. Meso-MNPs with a particle size ranging from 2 and 50 nm, a surface area of 140.52 m2 g-1, and a pore volume of 0.27 cm3 g-1 were synthesized on a porous SiO2 template in the presence of PEG 6000 followed by leaching of SiO2. Different ratios of meso-MNPs were successfully incorporated into chitosan:gelatin cryogels up to an amount equivalent to the entire amount of polymer. The morphological structure and physicochemical properties of the cryogels were directly affected by the amount of MNPs. VSM curves showed that all composite cryogels could be magnetized by applying a magnetic field. In the context of the safety of magnetic cryogel scaffolds for use in biomedicine, it is important to note that all values are below the exposure limit for static magnetic fields, and according to cytotoxicity data, scaffolds containing meso-MNPs showed nontoxicity with cell viability ranging from 150% to 275%. In addition, microbial analysis with gram-negative and gram-positive bacteria showed that the scaffolds exhibited activity against these bacteria.

In vitro osteogenesis of hMSCs on collagen membranes embedded within LEGO®-inspired 3D printed PCL constructs for mandibular bone repair

The field of bone tissue engineering aims to develop an effective and aesthetical bone graft substitute capable of repairing large mandibular defects. However, graft failure resulting from necrosis and insufficient integration with native tissue due to lack of oxygen and nutrient transportation remains a concern. To overcome these drawbacks, this study aims to develop a 3D printed polycaprolactone layered construct with a LEGO®-inspired interlocking mechanism enabling spatial distribution of biological components. To highlight itsin vitroosteogenic potential, human mesenchymal stromal cells are cultured onto Bio-Gide®Compressed collagen (Col) membranes, which are embedded within the layered construct for 28 d. The osteogenic response is assessed through the measurement of proliferation, relevant markers for osteogenesis including alkaline phosphatase (ALP) activity, expression of transcriptional genes (SP7, RUNX2/SOX9) as well matrix-related genes (COL1A1, ALPL IBSP, SPP1), osteoprotegerin secretion.In vitroosteogenic differentiation results showed increased levels of these osteogenic markers, indicating the layered construct's potential to support osteogenesis. In this study, a novel workflow of 3D printing a patient-specific LEGO®-inspired layered construct that can spatially deliver biological elements was successfully demonstrated. These layered constructs have the potential to be employed as a bone tissue engineering strategy, with particular focus on the repair of large mandibular defects.

Dual roles of photosynthetic hydrogel with sustained oxygen generation in promoting cell survival and eradicating anaerobic infection

Tissue engineering offers a promising alternative for oral and maxillofacial tissue defect rehabilitation; however, cells within a sizeable engineered tissue construct after transplantation inevitably face prolonged and severe hypoxic conditions, which may compromise the survivability of the transplanted cells and arouse the concern of anaerobic infection. Microalgae, which can convert carbon dioxide and water into oxygen and glucose through photosynthesis, have been studied as a source of oxygen supply for several biomedical applications, but their promise in orofacial tissue regeneration remains unexplored. Here, we demonstrated that through photosynthetic oxygenation, Chlamydomonas reinhardtii (C. reinhardtii) supported dental pulp stem cell (DPSC) energy production and survival under hypoxia. We developed a multifunctional photosynthetic hydrogel by embedding DPSCs and C. reinhardtii encapsulated alginate microspheres (CAMs) within gelatin methacryloyl hydrogel (GelMA) (CAMs@GelMA). This CAMs@GelMA hydrogel can generate a sustainable and sufficient oxygen supply, reverse intracellular hypoxic status, and enhance the metabolic activity and viability of DPSCs. Furthermore, the CAMs@GelMA hydrogel exhibited selective antibacterial activity against oral anaerobes and remarkable antibiofilm effects on multispecies biofilms by disrupting the hypoxic microenvironment and increasing reactive oxygen species generation. Our work presents an innovative photosynthetic strategy for oral tissue engineering and opens new avenues for addressing other hypoxia-related challenges.

Self-assembling Peptides Based Fibers: A Pioneering Innovation for Regenerative Medicine

Self-assembling peptides (SAPs) have emerged as a groundbreaking platform in regenerative medicine, offering innovative strategies for tissue engineering and repair. These biomolecules, designed to autonomously organize into nanofibers, mimic the natural extracellular matrix, providing essential structural support and biological cues for tissue regeneration. This review highlights the versatile applications of SAPs in regenerating diverse tissues, including bone, cartilage, cardiac, neural, and dermal structures, showcasing their potential to address a broad spectrum of medical challenges. The unique properties of SAPs, such as biocompatibility, biodegradability and specific cell receptor interaction capabilities, make them ideal for developing advanced therapeutic strategies. We discuss here the molecular design principles that allow for precise control over the nanofibers physical and chemical characteristics, facilitating the creation of scaffolds that promote cell attachment, proliferation, and differentiation. Additionally, the review covers the use of SAPs in drug delivery systems, emphasizing their ability to control the release of therapeutic agents, a critical aspect in enhancing tissue repair processes. Moreover, we address key considerations regarding the safety, biodegradability and potential immunogenicity of SAPs, underscoring the importance of thorough preclinical and clinical evaluations. The future directions and challenges in optimizing SAPs design and functionalization for maximizing regenerative outcomes are also explored.

Myotube formation on micropatterns guiding by centripetal cellular motility and crowding

The physical microenvironment, including substrate rigidity and topology, impacts myoblast differentiation and myotube maturation. However, the interplay effect and physical mechanism of mechanical stimuli on myotube formation is poorly understood. In this study, we utilized elastic substrates, microcontact patterning technique, and particle image velocimetry to investigate the effect of substrate rigidity and topological constraints on myoblast behaviors. Our findings suggested the interplay of substrate stiffness and cellular confinement improved the myotube formation by inducing centripetal cellular motility. These results shed light on the impact of the topological substrate on myoblast differentiation and emphasize the critical role of asymmetrical cell motility during this process, which is highly correlated with cell movement and crowding. Our research provides insights into the intricate interplay between substrate properties, cell motility, and myotube formation during myogenesis. Understanding these mechanisms could trigger tissue engineering strategies and therapies to enhance muscle regeneration and function.

Bioprinting of osteochondral tissues: A perspective on current gaps and future trends.

Osteochondral tissue regeneration has remained a critical challenge in orthopaedic surgery, especially due to complications of arthritic degeneration arising out of mechanical dislocations of joints. The common gold standard of autografting has several limitations in presenting tissue engineering strategies to solve the unmet clinical need. However, due to the complexity of joint anatomy, and tissue heterogeneity at the interface, the conventional tissue engineering strategies have certain limitations. The advent of bioprinting has now provided new opportunities for osteochondral tissue engineering. Bioprinting can uniquely mimic the heterogeneous cellular composition and anisotropic extra-cellular matrix (ECM) organization, while allowing for targeted gene delivery to achieve heterotypic differentiation. In this perspective, we discuss the current advances made towards bioprinting of composite osteochondral tissues and present an account of challenges—in terms of tissue integration, long-term survival, and mechanical strength at the time of implantation—required to be addressed for effective clinical translation of bioprinted tissues. Finally, we highlight some of the future trends related to osteochondral bioprinting with the hope of in-clinical translation.

Unconventional strategies for liver tissue engineering: plant, paper, silk and nanomaterial-based scaffolds.

The paper highlights how significant characteristics of liver can be modeled in tissue-engineered constructs using unconventional scaffolds. Hepatic lobular organization and metabolic zonation can be mimicked with decellularized plant structures with vasculature resembling a native-hepatic lobule vascular arrangement or silk blend scaffolds meticulously designed for guided cellular arrangement as hepatic patches or metabolic activities. The functionality of hepatocytes can be enhanced and maintained for long periods in naturally fibrous structures paving way for bioartificial liver development. The phase I enzymatic activity in hepatic models can be raised exploiting the microfibrillar structure of paper to allow cellular stacking creating hypoxic conditions to induce in vivo-like xenobiotic metabolism. Lastly, the paper introduces amalgamation of carbon-based nanomaterials into existing scaffolds in liver tissue engineering.

Human Chorionic Membrane-derived Tunable Hydrogels for Vascular Tissue Engineering Strategies.

One of the foremost targets in the advancement of biomaterials to engineer vascularized tissues is not only to replicate the composition of the intended tissue but also to create thicker structures incorporating a vascular network for adequate nutrients and oxygen supply. For the first time, to the best of current knowledge, a clinically relevant biomaterial is developed, demonstrating that hydrogels made from the human decellularized extracellular matrix can exhibit robust mechanical properties (in the kPa range) and angiogenic capabilities simultaneously. These properties enable the culture and organization of human umbilical vein endothelial cells into tubular structures, maintaining their integrity for 14 days in vitro without the need for additional polymers or angiogenesis-related factors. This is achieved by repurposing the placenta chorionic membrane (CM), a medical waste with an exceptional biochemical composition, into a valuable resource for bioengineering purposes. After decellularization, the CM underwent chemical modification with methacryloyl groups, giving rise to methacrylated CM (CMMA). CMMA preserved key proteins, as well as glycosaminoglycans. The resulting hydrogels rapidly photopolymerize and have enhanced strength and customizable mechanical properties. Furthermore, they demonstrate angio-vasculogenic competence in vitro and in vivo, holding significant promise as a humanized platform for the engineering of vascularized tissues.

Endogenous Tissue Engineering for Chondral and Osteochondral Regeneration: Strategies and Mechanisms.

Increasing attention has been paid to the development of effective strategies for articular cartilage (AC) and osteochondral (OC) regeneration due to their limited self-reparative capacities and the shortage of timely and appropriate clinical treatments. Traditional cell-dependent tissue engineering faces various challenges such as restricted cell sources, phenotypic alterations, and immune rejection. In contrast, endogenous tissue engineering represents a promising alternative, leveraging acellular biomaterials to guide endogenous cells to the injury site and stimulate their intrinsic regenerative potential. This review provides a comprehensive overview of recent advancements in endogenous tissue engineering strategies for AC and OC regeneration, with a focus on the tissue engineering triad comprising endogenous stem/progenitor cells (ESPCs), scaffolds, and biomolecules. Multiple types of ESPCs present within the AC and OC microenvironment, including bone marrow-derived mesenchymal stem cells (BMSCs), adipose-derived mesenchymal stem cells (AD-MSCs), synovial membrane-derived mesenchymal stem cells (SM-MSCs), and AC-derived stem/progenitor cells (CSPCs), exhibit the ability to migrate toward injury sites and demonstrate pro-regenerative properties. The fabrication and characteristics of scaffolds in various formats including hydrogels, porous sponges, electrospun fibers, particles, films, multilayer scaffolds, bioceramics, and bioglass, highlighting their suitability for AC and OC repair, are systemically summarized. Furthermore, the review emphasizes the pivotal role of biomolecules in facilitating ESPCs migration, adhesion, chondrogenesis, osteogenesis, as well as regulating inflammation, aging, and hypertrophy-critical processes for endogenous AC and OC regeneration. Insights into the applications of endogenous tissue engineering strategies for in vivo AC and OC regeneration are provided along with a discussion on future perspectives to enhance regenerative outcomes.

Using Laponite to Deliver BMP‐2 for Bone Tissue Engineering – In Vitro, Chorioallantoic Membrane Assay and Murine Subcutaneous Model Validation

AbstractFracture non‐union occurs due to various factors, leading to the development of potentially substantial bone defects. While autograft and allograft are the current gold standards for non‐union fractures, challenges related to availability and immune rejection highlight the need for improved treatments. A strategy in bone tissue engineering is to harness growth factors to induce an effect on cells to change their phenotype, behavior and initiate signaling pathways which lead to increased matrix deposition and tissue formation. Bone morphogenetic protein‐2 (BMP‐2) is a potent osteogenic growth factor however, given its rapid clearance time in vivo, there is a specific therapeutic window for efficacy while avoiding potential deleterious side‐effects. It is demonstrated that a Laponite nanoclay coating on a 3D printable and bioresorbable poly(caprolactone) trimethacrylate‐based resin enables binding of BMP‐2, decreases the rate of release, enabling reduced concentrations to be used while enhancing osteoinduction in both in vitro and in vivo models.

A New Tissue Engineering Strategy to Promote Tendon-bone Healing: Regulation of Osteogenic and Chondrogenic Differentiation of Tendon-derived Stem Cells.

In the field of sports medicine, repair surgery for anterior cruciate ligament (ACL) and rotator cuff (RC) injuries are remarkably common. Despite the availability of relatively effective treatment modalities, outcomes often fall short of expectations. This comprehensive review aims to thoroughly examine current strategies employed to promote tendon-bone healing and analyze pertinent preclinical and clinical research. Amidst ongoing investigations, tendon-derived stem cells (TDSCs), which have comparatively limited prior exploration, have garnered increasing attention in the context of tendon-bone healing, emerging as a promising cell type for regenerative therapies. This review article delves into the potential of combining TDSCs with tissue engineering methods, with ACL reconstruction as the main focus. It comprehensively reviews relevant research on ACL and RC healing to address the issues of graft healing and bone tunnel integration. To optimize tendon-bone healing outcomes, our emphasis lies in not only reconstructing the original microstructure of the tendon-bone interface but also achieving proper bone tunnel integration, encompassing both cartilage and bone formation. In this endeavor, we thoroughly analyze the transcriptional and molecular regulatory variables governing TDSCs differentiation, incorporating a retrospective analysis utilizing single-cell sequencing, with the aim of unearthing relevant signaling pathways and processes. By presenting a novel strategy rooted in TDSCs-driven osteogenic and chondrogenic differentiation for tendon-bone healing, this study paves the way for potential future research avenues and promising therapeutic applications. It is anticipated that the findings herein will contribute to advancing the field of tendon-bone healing and foster the exploration of TDSCs as a viable option for regenerative therapies in the future.

Research on the osteogenic properties of 3D-printed porous titanium alloy scaffolds loaded with Gelma/PAAM-ZOL composite hydrogels

Although titanium alloy is the most widely used endoplant material in orthopedics, the material is bioinert and good bone integration is difficult to achieve. Zoledronic acid (ZOL) has been shown to locally inhibit osteoclast formation and prevent osteoporosis, but excessive concentrations of ZOL exert an inhibitory effect on osteoblasts; therefore, stable and controlled local release of ZOL may reshape bone balance and promote bone regeneration. To promote the adhesion of osteoblasts to many polar groups, researchers have applied gelatine methacryloyl (Gelma) combined with polyacrylamide hydrogel (PAAM), which significantly increased the hydrogen bonding force between the samples and improved the stability of the coating and drug release. A series of experiments demonstrated that the Gelma/PAAM-ZOL bioactive coating on the surface of the titanium alloy was successfully prepared. The coating can induce osteoclast apoptosis, promote osteoblast proliferation and differentiation, achieve dual regulation of bone regeneration, successfully disrupt the balance of bone remodelling and promote bone tissue regeneration. Additionally, the coating improves the metal biological inertness on the surface of titanium alloys and improves the bone integration of the scaffold, offering a new strategy for bone tissue engineering to promote bone technology.

Antibacterial compounds-incorporated functional biomaterials for chronic wound healing application via 3D bioprinting: The mechanism of action

Wounds represent a critical issue in the healthcare industry since they are highly susceptible to infections that in turn lead to more serious complications. With bacterial infections gradually growing to be a challenge to wound healing, fighting bacterial resistance has become one of the important pillars of addressing issues faced by healthcare personnel. Thus, gaining an understanding of the distinct stages of wound healing is vital to further improve relevant therapies incorporating the application of antibacterial compounds. Recently, three-dimensional (3D)-printed functional biomaterials have emerged as an alternative treatment or potential carriers incorporating relevant antibacterial agents, offering a new approach to skin tissue engineering. Novel strategies for skin tissue engineering are grounded in the integration of bioactive ingredients and antibacterial agents into biomaterials with different morphologies to improve cell behaviors and promote wound healing by preventing bacterial colonization. This paper reviews the function of natural and synthetic polymers, effects of antibacterial properties, and cell interactions in terms of the wound healing process. Extensive research has demonstrated that 3D functional biomaterials exert their therapeutic effects through multifaceted pathways, including but not limited to, modulating inflammation, facilitating tissue regeneration, promoting cell proliferation, enhancing angiogenesis, and controlling infection. This review also provides general insights into the elegant design for 3D scaffold and further refinement of wound dressing.