Search Results (185)

Poor vascularization is one of the basic obstacles to the regeneration of functioning tissues because an oxygen diffusion process and elimination of wastes are essential in preserving the grafts. Recently, biomaterials have allowed the invention of bioinspired polymer scaffolds and replicated the natural extracellular matrix (ECM) due to the mechanical tunability of the synthetic polymers with the biological signals of natural macromolecules. The review uses a mechanistic analysis of the strategies to improve angiogenesis by using surface topography modification, bioactive peptide incorporation and pre-vascularization. Another way to achieve complex, perfusable topologies is by using more sophisticated methods of fabrication, such as electrospinning, 3D/4D bioprinting, or microfluidics. Based on in vitro and in vivo results, we determine angiogenic effectiveness by using cellular assays and animal transfers, pointing towards the translational advances in patents and clinical uses of bone, cardiac, nervous, and skin tissues. In spite of the substantial improvements, large-scale production and high demands of the regulations still exist. The future directions include the incorporation of bioinspired designs and intelligent materials, nanotechnology, and AI-based optimization into developing patient-specific and adaptive scaffolds. The following innovations herald the advent of highly effective constructs that can be used to regenerate tissue and overcome the limitations of present tissue engineering therapies through the introduction of highly effective, vascularized constructs. Full article

Severe skin injury in humans typically heals through fibrotic remodelling rather than true regeneration, resulting in permanent loss of appendages, sensory function, and tissue architecture. Over the past decades, advances in bulk, single-cell, and spatial transcriptomic profiling have revealed that cutaneous wound repair is governed by dynamic, context-dependent gene-regulatory programmes across epidermal, dermal, vascular, and immune compartments. These studies highlight substantial heterogeneity in keratinocyte, fibroblast, and immune cell states, and identify RNA-mediated regulatory networks that bias healing toward either regenerative or fibrotic outcomes. In parallel, stem cell-derived skin organoids and advanced engineered skin equivalents have emerged as experimental platforms capable of reproducing key aspects of human skin organisation, offering new opportunities to move beyond purely reparative grafting strategies. This review integrates evidence from human or murine skin and wound transcriptomics, RNA-based regulatory mechanisms, and organoid-based skin engineering relevant to trauma and burn reconstruction. We summarise how protein-coding and non-coding RNAs (including miRNAs and lncRNAs) coordinate epithelial migration, inflammation resolution, angiogenesis, and ECM remodelling, and how the dysregulation of these networks contributes to pathological scarring. This article synthesises transcriptomic, RNA regulatory, and skin organoid research to propose a conceptual, hypothesis-generating framework for regenerative skin repair, without claiming clinical readiness or validated therapeutic translation. Full article

Solution electrospinning (SES) and melt electrowriting (MEW) are complementary fiber-based fabrication platforms extensively investigated in tissue engineering. SES generates fibers typically ranging from the nanometer to the low-micrometer scale, producing fibrous networks that mimic the native extracellular matrix (ECM) and support key cellular functions. MEW, by contrast, operates solvent-free and enables precise, layer-by-layer deposition of microfibers with well-controlled geometry, conferring the mechanical integrity and open-pore architecture that SES constructs inherently lack. Despite growing interest, the body of peer-reviewed literature reporting original hybrid SES–MEW fabrication and biological outcome data remains limited, with no comprehensive cross-tissue synthesis available to date. This narrative review examines the current state of SES–MEW hybrid strategies across five tissue engineering targets selected for their clinical relevance: skin, vascular grafts, bone, cartilage, cardiac valves, and skeletal muscle. For each application, the architectural rationale, the fabrication approach, and the in vitro and in vivo biological outcomes are discussed in an integrated manner, with attention to how the spatial organization of nano- and microfibers translates into tissue-specific functional responses. A comparative analysis across tissue types highlights both the versatility of hybrid constructs and their persistent limitations, including suture retention values that remain below clinically accepted thresholds in vascular applications, incomplete cellular infiltration through dense nanofibrous layers, and the absence of validated, reproducible scale-up protocols compatible with clinical-grade manufacturing. The review concludes by identifying the most critical open questions in the field, encompassing process standardization, regulatory classification, and the emerging role of machine learning in closed-loop MEW process optimization. This work aims to provide an evidence-based perspective on the current state of hybrid SES–MEW scaffold engineering and the key translational gaps limiting clinical application. Full article

Mineral powder–based bone grafts exhibit excellent osteoconductivity; however, their clinical efficacy is often compromised by insufficient early-stage tissue ingrowth, leading to particle aggregation and pocket formation within the defect site during the initial healing phase. Here, we report a cotton-type nanofiber-guided mineral graft designed to overcome this early integration failure by creating fibrous pathways for tissue ingress. Cotton-type polycaprolactone (PCL) nanofibers were fabricated via electrospinning using a pin-based collector engineered to induce strong inter-fiber repulsion, resulting in a highly expanded, three-dimensional cottony architecture. Tetracalcium phosphate (TTCP) and α-tricalcium phosphate (α-TCP) mineral particles were subsequently deposited onto the surface of the cottony nanofibers, forming a fibrous–mineral hybrid graft (c-NF@T/α-TCP) in which the nanofibers act as a transient, functionally defined tissue-guiding framework during the early healing phase. The cottony nanofiber network effectively prevented mineral particle aggregation and generated continuous pathways within the graft, facilitating early tissue infiltration and vascular ingress during the first week after implantation. In vivo evaluation in a bone defect model demonstrated that c-NF@T/α-TCP significantly reduced tissue pocket formation at early time points and promoted subsequent bone regeneration compared to mineral powder-only grafts. This study highlights the critical importance of early-stage structural guidance in mineral-based bone grafts and introduces cotton-type nanofiber–guided pathway engineering as a simple yet effective strategy to unlock the regenerative potential of conventional inorganic bone substitutes. Full article

Background: Coronary artery bypass grafting is the optimal revascularization strategy for patients with complex multivessel coronary artery disease. However, saphenous vein grafts are associated with high failure rates and donor site morbidity. Off-the-shelf tissue-engineered vascular grafts offer a potential solution for patients lacking suitable autologous vessels. Here, we report the first successful clinical implant of an acellular Tissue-Engineered Vessel (TEV) for coronary artery bypass grafting in Europe. Methods: A 73-year-old male with two-vessel disease and no suitable autologous vein underwent on-pump coronary artery bypass grafting using the left internal mammary artery to the left anterior descending artery and a 4 mm TEV to the right coronary artery. Results: Implant procedure followed standard surgical techniques, sutures and duration. The conduit handling was comparable to native vessels. Intraoperative flow measurements demonstrated excellent graft performance (TEV: 110 mL/min, Pulsatility Index 1.0). Postoperative recovery was uneventful. One-month computed tomography coronary angiography confirmed graft patency. Discussion: This case demonstrates the feasibility of using a bioengineered conduit for coronary revascularization in patients without suitable autologous grafts. If these findings are confirmed in larger trials, bioengineered vessels could expand surgical revascularization to patients without suitable autologous conduits and fundamentally alter conduit selection strategy in CABG. Conclusions: This first-in-Europe clinical implant demonstrates that an off-the-shelf acellular tissue-engineered vessel can meet the procedural, hemodynamics, and patency requirements of coronary artery bypass. These proof-of-concept results support progression to prospective multi-center evaluation. Full article

Reconstruction of craniomaxillofacial (CMF) bony defects requires individualized strategies based on defect characteristics and graft bed biology, with traditional approaches relying on autogenous non-vascularized bone grafts or vascularized free flaps that, while reliable, are associated with donor-site morbidity and operative complexity. Biologically driven reconstructive strategies, including tissue engineering, cellular bone matrix allografts (CBMs), and growth factor adjuncts, have emerged as alternatives or complements to autograft-based reconstruction. This review introduces and details these new innovations with emphasis on the current literature, thus empowering surgeons to enhance their clinical armamentarium. Full article

Hydrogel-based products are used in many areas of biomedicine and healthcare. Recently, the incorporation of cellulose nanocrystals (CNC), a renewable and functional nanomaterial, into hydrogels has enhanced their functionality, particularly by imparting mechanical strength and structural integrity. This scoping review aims to appraise the types of biomedical models and assays that have been utilised to investigate the effects of CNC incorporation into hydrogels in tissue engineering, wound healing, medical implantation and drug delivery applications, and reports on the rationale for including these models and assays. A structured literature search was undertaken in major scientific databases (PubMed Central, PubMed, BioMed Central, ScienceDirect, Wiley and EBSCOhost), focusing on identifying primary research published between 2016 and 2024. From this process, fifteen studies providing biomedical analyses met the inclusion criteria. Most of these investigations employed in vitro cell-line models (n = 12), with a smaller number utilising in vivo experimental systems (n = 5). Across the included studies, CNC incorporation typically yielded measurable performance gains: reported compressive or storage modulus improvements of 20–40% over hydrogel-only controls, consistently high cell viability (>85%) across multiple human and murine cell types for up to 21 days, and sustained drug release profiles (days–weeks) in stent and antitumour contexts. Where quantified, functional outcomes in vivo included preserved graft volume (autologous fat grafts) and reduced intimal hyperplasia signals in vascular graft models. Critical gaps included heterogeneous CNC sources and surface chemistries, inconsistent reporting of CNC concentration and hydrogel formulation parameters, the limited duration and scope of biocompatibility testing, and minimal alignment with standard evaluation protocols, constraining reproducibility and cross-study comparability. To date, there are no human clinical trials of CNC-hydrogels. Translational readiness will require standardised ISO-compliant biocompatibility evaluations. Large-animal studies under relevant mechanical and physiological conditions, and rigorous long-term degradation and immunogenicity assessments to de-risk progression to human trials. We recommend standardised CNC sources and surface functionalisation reporting, concentration (wt%) ranges, hydrogel rheological characterisation (G′, G″, swelling), and consistent biological endpoints (viability, differentiation, inflammation panels) to enable robust meta-analyses and translational benchmarking. Distinct from prior nanocellulose reviews that emphasise material synthesis and properties, this analysis centres on the biomedical models and assays applied to CNC-incorporated hydrogels, identifying the methodological convergence and divergence that directly impact translational pathways. Full article

Tissue-engineered vascular grafts (TEVGs) represent a promising alternative for coronary artery bypass grafting (CABG). However, replicating the mechanical and biological complexity of native vessels remains a major challenge. Compliance mismatch, local hemodynamics, and insufficient endothelialization are recognized as key contributors to maladaptive remodeling and graft failure. These limitations highlight the urgent need for advanced experimental platforms and standardized physical stimulation procedures to investigate these underlying biomechanisms and support the development of more effective TEVGs. In this work, we present an automated, modular platform designed to quantitatively characterize graft compliance and replicate coronary hemodynamics. The system integrates automated experimental procedures within a modular, incubator-compatible design, enabling an intuitive setup and real-time monitoring of physical parameters. Its modular architecture and dedicated control algorithms provide high adaptability, enabling its application across a broad range of experimental conditions. Bench testing demonstrates that the platform can automatically reproduce the pressure regimes defined by ISO standard and generate coronary-like flow-induced stimuli. These results confirm the innovative capability of the system to provide controlled and physiologically relevant conditions suitable for the investigation of key phenomena involved in CABG failure. In perspective, the platform offers a valuable tool for advanced mechanobiological studies in vascular tissue engineering. Full article

Reliable vascular access remains a major clinical challenge for hemodialysis patients, as expanded polytetrafluoroethylene (PTFE) grafts exhibit poor patency and frequent complications driven by thrombosis and neointimal hyperplasia. Tissue-engineered vascular grafts offer a regenerative alternative but often lack the mechanical resilience required for high-flow arteriovenous (AV) environments. Here, we developed a reinforced, biofunctionalized coaxial electrospun graft comprising a poly(ε-caprolactone) mechanical core and a norbornene-functionalized poly(ethylene glycol) sheath incorporating pro-endothelialization cues. Circumferential PTFE rings were added to improve kink resistance. Grafts were implanted in a porcine AV configuration that recapitulates clinical hemodynamic conditions. Mechanical characterization included compliance, burst pressure, and kink resistance; host remodeling was assessed using histology, immunofluorescence, and multiphoton imaging at 4 weeks. Ring-reinforced electrospun grafts demonstrated a kink radius of 0.187 cm, compliance of 1.04 ± 0.29%/100 mmHg, and burst pressure of 1505 ± 565 mmHg, values all comparable to Gore-Tex PTFE and within industrial performance standards. In vivo, the electrospun grafts showed extensive host cell infiltration, collagen deposition, and formation of smooth muscle-like tissue, whereas PTFE controls remained largely acellular. Immunofluorescence confirmed intramural α-SMA⁺ and CD31⁺ cell populations, and multiphoton microscopy revealed significantly greater collagen and elastin content compared with PTFE (p < 0.05). Collectively, these findings demonstrate that the reinforced electrospun graft maintains mechanical integrity under physiological AV loading while supporting in situ endothelialization and extracellular matrix remodeling in a clinically relevant, large animal model. This work provides one of the first demonstrations of functional tissue regeneration within a fully synthetic, acellular scaffold in a porcine hemodialysis model and advances the translational development of durable, regenerative vascular access grafts that couple mechanical resilience with bioactive healing capacity. Full article

Pancreatic β-cell replacement represents a promising therapeutic avenue for insulin-dependent diabetes, yet clinical translation has been limited by donor scarcity, immune rejection, and incomplete engraftment. Three-dimensional (3D) pancreatic organoids derived from human pluripotent stem cells (hPSCs) or primary tissue offer a scalable and physiologically relevant platform, recapitulating native islet architecture, paracrine interactions, and glucose-responsive insulin secretion. Recent advances in differentiation protocols, vascularization strategies, and immune-protective approaches—including encapsulation and hypoimmunogenic engineering—have enhanced β-cell maturation, survival, and functional performance in vitro and in vivo. Despite these developments, challenges remain in achieving fully mature β-cells, durable graft function, and scalable, reproducible production that is suitable for clinical use. This review highlights the promise of pancreatic organoid engineering, emphasizing strategies to optimize β-cell maturation, vascular integration, and immune protection, and outlines key future directions to advance organoid-based β-cell replacement toward safe, effective, and personalized diabetes therapies. Full article

Vascularization is one of the key components of tissue engineering and must accompany the ingrowth of new tissues to establish an environment conducive to repair and regeneration of damaged tissue. The overarching objective of this study was to investigate whether the hyper-crosslinked carbohydrate polymer (HCCP) could promote the establishment of new vasculature compared to hydroxyapatite/beta-tricalcium phosphate (HA/β-TCP), which is widely used in orthopedic procedures. Sprague Dawley rats (n = 12) were implanted subcutaneously with HCCP or HA/β-TCP and evaluated histologically for the ingrowth of new vasculature at 3, 14, and 28 days post-implantation. HCCP showed significantly greater levels of vascularization when compared to HA/β-TCP at all time points evaluated (p < 0.05). HA/β-TCP showed transient inflammation at 14 days post-implantation, whereas minimal immune activities were noted in HCCP. These findings suggest that HCCP promotes the establishment of new vasculature without a significant immune response. Full article

Small-diameter vascular grafts (SDVGs, ≤6 mm) face significant barriers in vascular reconstruction due to poor long-term patency stemming from thrombosis, intimal hyperplasia, and mechanical mismatch. Increasing rates of cardiovascular disease and limited autologous vessel supply underscore the urgent need for functional SDVGs. This review discusses the critical failure mechanisms of SDVGs and recent material-based advances—hydrophilic modifications, charge control, micro- and nano-engineering, antimicrobial and anti-inflammatory treatments, and controlled bioactive release (e.g., heparin, nitric oxide, t-PA). It details progress in cellular and tissue engineering for rapid endothelialization, smooth muscle regeneration, and mechanical durability. The review also highlights emerging gene engineering, the use of bioactive peptides, and molecular pathway strategies for physiological antithrombotic restoration. Finally, it outlines future directions, including smart materials, accelerated endothelialization, advanced manufacturing (3D printing, multilayer electrospinning), multifunctional composites, and clinical translation. Overall, SDVG research is shifting toward active, regenerative vascular substitutes with improved clinical prospects. Full article

Craniofacial bone defects of critical size, caused by trauma, tumors, infections, or congenital maldevelopment, represent a major challenge in plastic and reconstructive surgery. Autologous bone grafting is considered the gold standard, but limitations such as donor site morbidity and limited availability have prompted the development of artificial bone tissue engineering scaffolds. In recent years, bioactive scaffolds have been increasingly utilized in favor of inert biomaterials due to their immunomodulation and osteoinduction capabilities. This review methodically summarizes loading strategies for the functionalization of scaffolds with bioactive components, including cell regulatory factors, drugs, ions, stem cells, exosomes, and components derived from human tissues or cells to promote bone regeneration. The following mechanisms are involved: (1) the polarization of macrophages (M1-M2 transition), (2) the dynamic regulation of bone metabolism, and (3) the coupling of osteogenesis and angiogenesis. This review focuses on innovative delivery systems, such as 3D-printed scaffolds, nanocomposites and so on, that enable spatiotemporal control of bioactive cargo release. These address key challenges, such as infection resistance, vascularization, and mechanical stability in the process of bone regeneration. In addition, the article discusses emerging technologies, including stem cells and exosome-based acellular therapies, which demonstrate potential for personalized bone regeneration. This review integrates immunology, materials science, and clinical needs, providing a roadmap for the design of next-generation bone tissue engineering scaffolds to overcome critical-sized bone defects. Full article

Background: The integration of 3D bioprinting, biomaterials science, and cellular biology presents a viable strategy for maxillofacial bone regeneration, overcoming the constraints of traditional graft techniques. This review offers a thorough examination of the present condition, obstacles, uses, and future outlook of 3D bioprinting technology in maxillofacial bone regeneration. An essential understanding has been attained by analyzing the technological constraints, specifically in vascularization and neuro-integration, and by delineating the vital translational pathway from benchtop models to clinical application. We have examined several bioprinting techniques—namely extrusion, inkjet, and laser-assisted methods—and the requisite bioinks, emphasizing their physicochemical and biological features vital for osteogenesis. Significant clinical applications, including the treatment of trauma-induced abnormalities and the reconstruction of oncology-related resections, have been emphasized. This review highlights the urgent necessity for established regulatory frameworks and refined printing settings to guarantee effective, functional, and durable bone substitutes, providing a distinct pathway for future research and clinical implementation in this specialized surgical domain. Aim: The purpose of this review was to present a general overview of the current clinical and diagnostic applications of bioprinting in bone tissue engineering for the reconstruction of bone defects. Methods: A search of major scientific databases, including PubMed, Science Direct, Embase, and Cochrane, was conducted. Articles published within the last 10 years that analyze the possible applications of bioprinting in bone tissue fabrication were included. Results: Several bioinks, based on hydrogels and stem cells, can enable the fabrication of such tissues using this technology. This review reports on the processes adopted for the bioprinting of bone tissue, the bioinks used, and cell cultivation methods. Conclusions: Bioprinting represents a promising solution for bone regeneration with potential applications that could revolutionize current surgical practices, despite the many challenges that future research will face. Full article

The critical shortage of donor organs remains the foremost challenge in transplantation medicine. Nevertheless, advancements in robotic-assisted surgery (RAS), artificial intelligence (AI)-enhanced donor–recipient matching, and bioengineering—particularly 3D bioprinting—are revolutionizing the field. Today, RAS has evolved from an innovative technique into a reliable clinical tool, with evidence indicating that it enhances surgical precision and results in better patient outcomes. Meanwhile, AI and machine learning are advancing donor–recipient matching and allocation, producing models that offer superior predictive accuracy for graft survival compared to traditional methods. Additionally, bioengineering strategies, especially 3D bioprinting and tissue engineering, are progressing from the creation of acellular scaffolds to the development of vascularized constructs, marking a significant milestone toward functional organ replacement. Despite persistent challenges such as high costs, regulatory obstacles, new structured formation programs, and the necessity for effective vascularization in engineered tissues, the integration of these disciplines is forging a new paradigm in regenerative medicine. The primary objective of this review is to synthesize multidisciplinary innovations by leveraging clinical studies and technological assessments to delineate future directions in regenerative medicine and organ transplantation. Full article