Search Results (4,823)

Bone tissue engineering requires biomimetic materials; however, pure polylactic acid (PLA) exhibits limited osteoinductivity and produces acidic byproducts upon degradation. To address these limitations, this study fabricated PLA scaffolds using fused-deposition modeling (FDM) with four distinct lattice structures (rectangular, triangular, gyroid, and 3D honeycomb) and incorporated hydroxyapatite (HA) at 0, 10, 20, and 30 wt% via injection molding. Mechanical properties were evaluated via compression, three-point bending, and tensile testing. The results revealed that increasing HA content significantly reduced structural strength and increased brittleness across all test modes. Specifically, specimens with 30 wt% HA exhibited a 70.8% reduction in bending strength relative to pure PLA (from 58.60 MPa to 17.07 MPa), while tensile strength decreased by 46.1% at just 10 wt% HA (from 37.54 MPa to 20.23 MPa). Although the triangular lattice achieved the highest absolute compressive load, the rectangular lattice provided a superior load-to-weight ratio and greater plastic deformation capacity before fracture. Consequently, these findings indicate that the rectangular pattern at 70% infill density combined with HA addition limited to ≤10 wt% represents the most mechanically balanced design for bone defect repair applications. Based on the mechanical characterization performed in this study, and drawing on published evidence regarding the biological properties of PLA/HA composites, these scaffolds represent a mechanically promising candidate for further evaluation in bone tissue regeneration. Biological validation through in vitro and in vivo studies is required before clinical relevance can be established. Full article

Annually, there are more than two million deaths from liver disease. This is driven by organ inflammation and scarring, leading to a decline in function and regeneration. Frequently, this can develop into decompensated liver disease, resulting in the loss of physiological balance and toxin build-up within the body, with an increased risk of patient mortality. Currently, there are no approved medicines for the long-term treatment of liver cirrhosis. The only successful treatment option for end-stage liver disease patients is donor organ transplantation. However, patient requirement outstrips the number of donated organs. To address this bottleneck, researchers around the world have developed cell-based prototype systems to restore failing liver function, with some in clinical trials. Although significant progress has been made, no mainstream commercial liver assist products are available for routine clinical use. In this study we developed a stem cell-derived vascularized liver tissue implant prototype from pluripotent cells. The liver tissue was produced from a stem cell line that is banked at clinical grade, and displayed stable and mature liver function over a 6-week period in vitro. This included decreasing levels of the fetal marker, alpha-fetoprotein, when the serum albumin increased. This was further supported by stable alpha-1-antitrypsin secretion and cytochrome P450 function. Following the establishment of stable liver tissue, it was delivered as a cell product or attached to an electrospun polycaprolactone scaffold, to form a tissue implant. Next, cellular material was quality-controlled, and subsequently shipped to a contract research organization for external in vivo validation. The transplanted liver tissue functioned when implanted into the kidney capsule and subcutaneously, remaining functional for up to two weeks in vivo. Full article

Hydrogel scaffolds have emerged as a central platform in tissue engineering due to their ability to mimic the extracellular matrix and support cellular functions. Among natural polymers, chitin and its derivative chitosan have emerged as valuable candidates for hydrogel scaffold development because of their biodegradability, compatibility with living tissues, and inherent biological functionality; however, their distinct and complementary roles in hydrogel scaffold design are often insufficiently differentiated in the literature. This review provides a comprehensive and mechanism-driven analysis of chitin- and chitosan-based hydrogel scaffolds, emphasising how their molecular structure governs network formation, mechanical performance, and biological functionality. Chitin is highlighted primarily as a structurally robust and crystalline component suitable for reinforcement. In contrast, chitosan serves as a versatile, soluble, and chemically reactive matrix enabling various crosslinking and functionalization strategies. Recent advances in physical, ionic, and covalent crosslinking as well as composite scaffold engineering, biofunctionalization, and emerging fabrication approaches such as injectable systems and three-dimensional bioprinting are systematically examined. The relationships between scaffold architecture, degradation behaviour, and cellular responses are discussed in key tissue engineering applications, including bone, cartilage, skin, and nerve regeneration. Importantly, this review introduces a unified structure–property–function framework that distinguishes the roles of chitin and chitosan within hydrogel systems and links crosslinking mechanisms to application-specific performance requirements, an aspect not comprehensively addressed in previous studies. Current challenges related to mechanical limitations, material variability, and clinical translation are critically evaluated, and future perspectives for the rational design of next-generation biomimetic hydrogel scaffolds are proposed. Full article

Bletilla striata polysaccharide (BSP), a bioactive glucomannan derived from the traditional Chinese medicinal herb Bletilla striata, has garnered increasing attention in both the biomedical and food sectors due to its unique physicochemical properties and diverse biological activities. While existing reviews have partially covered BSP’s structural features or single-field applications, a systematic review integrating its structure–activity relationship, full-spectrum chemical modification strategies, and parallel advances in the dual core fields of biomedicine and the food industry remains lacking. This review systematically consolidates recent advances in BSP research, focusing on three interconnected aspects: (1) the structure–activity relationships of BSP, highlighting how molecular weight (10⁴–10⁵ Da), monosaccharide composition (mainly glucose and mannose with variable ratios), glycosidic linkages, and higher-order self-assembled structures (e.g., triple-helix conformation) dictate its functionality in biological systems and food matrices; (2) chemical modification strategies—including carboxymethylation, graft copolymerization, cross-linking, polysaccharide–trace element complexation, phosphorylation, acetylation, and cholesterylation—that overcome intrinsic limitations of native BSP to enhance solubility, targeting, bioactivity, and food-related functional properties; and (3) the expanding applications of BSP and its derivatives in biomedicine (hemostatic materials, tissue engineering scaffolds, drug delivery systems, immunomodulation, and antitumor effects) and in the food industry (as natural stabilizers, emulsifiers, functional additives, and bio-based packaging components). Compared with previously published reviews, this work establishes a complete closed-loop logical system from structural characterization to rational modification and cross-field application and provides the most up-to-date systematic summary of BSP research. Key challenges—such as an incomplete understanding of structure-function correlations, insufficient pharmacokinetic data, and a lack of standardized quality control—are discussed, and future research directions are proposed. This review aims to provide a systematic theoretical basis for advancing BSP as a versatile multifunctional material for applications in functional foods, nutraceuticals, and biomedical fields. Full article

Chronic liver disease remains a major global health burden, with liver transplantation as the only definitive therapy despite severe limitations in donor availability, surgical morbidity, and patient eligibility. Although the liver has substantial intrinsic regenerative capacity, endogenous repair is often insufficient in chronic injury, cirrhosis, and acute-on-chronic liver failure. As a result, regenerative strategies that restore liver function without whole-organ replacement are increasingly pursued. This review examines controlled release biomaterial-based liver regeneration platforms, particularly those that utilize hydrogels and/or complementary nanoparticle systems, as clinically practical tools to enhance endogenous regeneration. We include discussion of both 3D scaffold-based and injectable hydrogels to enhance regeneration. Used as biological support and controlled release mixtures, they enable local retention, entrapping and controlling the release of regenerative cues including growth factors (HGF, EGF, etc.), nucleic acids for gene expression, stem cells or other cell populations, and conditioned extracellular vesicles, overcoming poor cell engraftment, short cytokine half-lives, and other limitations. Further, synthetic nanoparticles can structure release at the protein/molecular level as well as catalytically modulating oxidative stress and inflammation. Within the context of these systems, we structure the anatomical, engineering, and imaging considerations essential for the clinical translation of gel composite systems while highlighting remaining barriers to wider clinical adoption. Collectively, these advances position biomaterial-enabled regenerative therapies as a realistic alternative or bridge to donor restricted liver transplantation. Full article

Multifunctional scaffolds that combine structural support with the controlled delivery of bioactive agents remain a major challenge in tissue engineering. To extend the use of these devices in biomedicine, 3D printing is presented as an alternative that enables the manufacture of complex devices tailored to each patient, thereby solving specific problems in a timely and efficient manner. In this study, porous 3D scaffolds were fabricated via digital light processing (DLP) using a PET-RAFT resin composed of 2-(dimethylamino)ethyl methacrylate (DMAEMA) and poly(ethylene glycol) diacrylate (PEGDA₅₇₅). Sodium chloride (NaCl) was incorporated as a porogen, while insulin-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles were embedded as osteoinductive agents. The printed constructs exhibited high-resolution, reproducible trabecular-like architectures, as confirmed by micro-computed tomography (micro-CT), with interconnected pores averaging 70.7 ± 24.7 μm and a total porosity of 57.0 ± 6.98%. Thermal and chemical analyses confirmed scaffold stability and controlled degradability. Cytocompatibility assays using MC3T3-E1, C2C12, hGMSCs, and C166-GFP cells showed viability above 80% after 7 days (ISO 10993-5). Insulin-loaded nanoparticles enabled sustained release, characterized by an initial burst followed by gradual release up to 72 h. Dynamic bioreactor culture enhanced cell adhesion and RUNX2 expression, confirming the osteoinductive potential of the hybrid scaffold for advanced BTE applications. This study introduces an innovative PET-RAFT-derived resin that combines structural reinforcement with spatiotemporal regulation of insulin release, offering a potential strategy for enhanced biomaterial tissue engineering and tailored therapeutic interventions. Full article

Background: Impaired angiogenesis and persistent inflammation are hallmarks of chronic diabetic wounds. Extracellular vesicles derived from dental pulp stem cells (DPSC-EVs) represent a promising cell-free therapy for tissue repair; however, their clinical translation is hindered by suboptimal yields and attenuated bioactivity associated with conventional two-dimensional (2D) culture. This study investigated whether a biomimetic three-dimensional (3D) fibrin/gelatin hydrogel system could optimize the therapeutic potency of DPSC-EVs for diabetic wound healing. Methods: DPSCs were encapsulated within 3D fibrin/gelatin scaffolds, followed by comprehensive characterization of cell viability and morphology. 3D-EVs and 2D-EVs were isolated via ultracentrifugation and validated by transmission electron microscopy and nanoparticle tracking analysis. The pro-angiogenic capacity of 3D-EVs was evaluated using human umbilical vein endothelial cells (HUVECs) under high-glucose (HG) stress. Additionally, the immunomodulatory effects were assessed by monitoring macrophage polarization in lipopolysaccharide-stimulated RAW 264.7 cells. The therapeutic efficacy was further validated in vivo using a streptozotocin (STZ)-induced diabetic mouse model with full-thickness cutaneous wounds. Results: The 3D fibrin/gelatin hydrogel provided a supportive microenvironment that significantly augmented the secretory productivity of DPSCs. Compared to 2D-EVs, 3D-EVs exhibited superior functional resilience in restoring HUVEC migration and tube formation under HG-induced oxidative stress. Furthermore, 3D-EVs effectively orchestrated the macrophage transition from a pro-inflammatory M1 phenotype toward an anti-inflammatory M2 phenotype, thereby modulating the immune microenvironment. In vivo, topical administration of 3D-EVs markedly accelerated wound closure, promoted re-epithelialization, and enhanced microvascular density and collagen maturation in diabetic mice. Conclusions: Our findings demonstrate that the 3D fibrin/gelatin culture system effectively primes the therapeutic profile of DPSC-EVs. These engineered vesicles accelerate diabetic wound healing by synergistically promoting angiogenesis and resolving chronic inflammation, offering a robust and potent cell-free strategy for the management of chronic diabetic ulcers. Full article

Spi-1 Proto-Oncogene (SPI1) encodes Purine-rich box 1 Transcription Factor (PU.1), a transcription factor of the ETS family that regulates hematopoietic lineage commitment and immune cell differentiation. Alteration of PU.1 dose or ETS domain integrity may interfere with transcriptional programs, which adds to hematopoietic dysregulation and leukemogenesis. Even though changes in SPI1 expression have been associated with acute myeloid leukemia (AML), the structural and regulatory effects of missense mutations at the PU.1 ETS domain have not been entirely studied, and targeting the PU.1 ETS domain by ligands is an area of computational analysis that should be further pursued. To computationally describe deleterious missense variants of SPI1 in terms of structural stability, evolutionary conservation, post-translational modification (PTM) context and interaction networks, and to measure ADMET-mediated molecular docking of cinnamic acid with the PU.1 ETS domain (8EQG) as a potential modulator. Missense nsSNPs were obtained through Ensembl and narrowed down by consensus prediction of pathogenicity (PredictSNP, combining SIFT, PolyPhen, SNAP and PhD-SNP and other tools). InterPro/UniProt was used for domain mapping. SWISS-MODEL was used to produce wild-type and mutant PU.1 versions, which were analyzed on the structural alignment and Cα–Cα displacement parameters in UCSF Chimera (v1.19). The estimation of stability change was carried out with I-Mutant and MUpro. Prediction of PTM sites was done using MusiteDeep and exploration of functional partners was done using STRING. Human, mouse and zebrafish orthologue conservation was measured by means of MAFFT alignment. GEPIA2 was used to compare the expression of SPI1 in AML (TCGA-LAML) and normal tissues (GTEx). AutoDock Vina (grid center 6, −2, −9 A; 20 × 20 × 20 A; 16 exhaustiveness) was used to prepare cinnamic acid and dock it into the PU.1 ETS domain (8EQG), with SwissDock being used for consistency checks. SwissADME and ADMETlab 2.0 were used to predict drug-likeness, pharmacokinetics, and toxicity. Nine missense mutations were routinely considered as deleterious with the majority of them being located in or near the ETS DNA-binding domain. Structural comparisons showed local perturbations of the structure and I189F and H211P yielded the greatest conformational changes between prioritized variants whereas other forms had minimal movements. A predominantly destabilizing trend was supported by stability prediction whereby V241G had the strongest destabilization signal with further destabilizations being predicted in I189F and R259C. PTM mapping revealed several potential regulatory residues (phosphorylation, acetylation, ubiquitination, and methylation), which indicated that there could be crosstalk between the sequence variation and the transcriptional regulation. The SPI1 was placed in a central hematopoietic transcriptional module (containing RUNX1, CEBP members, GATA1 and IRF factors) by the STRING network. The cross-species alignment showed that there was high conservation of a number of the mutation sites, which would support functional constraint at the ETS region. The expression analysis revealed that the level of SPI1 mRNA in AML was significantly elevated compared to normal tissues. Docking also indicated a slight and reproducible interaction of cinnamic acid with the ETS domain (top affinity −4.27 kcal/mol), with a solitary leading polar anchor and supportive hydrophobic interactions, which is akin to interaction between fragments. The ADMET profiling revealed the likelihood of success in the oral drug-likeness and low CYP inhibition liability, as well as signifying the presence of a possible hepatotoxicity signal that needs further confirmation through experiments. Comprehensive computational studies suggest that certain pathogenic variants of SPI1 missense defects, especially in the ETS domain, can result in loss of PU.1 structural stability and regulatory environment, which are in line with the disturbed hematopoietic regulation and AML-related dysregulation. Cinnamic acid demonstrates moderate yet reproducible binding to the PU.1 ETS domain and has an overall favorable developability profile, which indicates that it is better considered as a starting scaffold, as opposed to an active inhibitor. The results give a logical basis of focused biochemical validation and structure-directed optimization of ETS domain modulators in hematologic disease settings. Full article

Objective: Effectively eliminating xenoimmunogenicity and achieving recellularization in cardiac xenografts remains a critical challenge in developing an ideal implantable xenograft. We have previously demonstrated that the removal of major antigens, including Galα1-3Gal (α-Gal) epitope and non-human sialic acid N-glycolylneuraminic acid (Neu5Gc), using α-galactosidase and peptide N-glycosidase F (PNGase-F), enables a synergistic effect with decellularization, significantly reducing the expression of carbohydrate-binding lectins without altering the biomechanical properties of the graft. The aim of this study was to establish an effective method for in vitro recellularization by seeding human mesenchymal stem cells (MSCs) on decellularized cardiac xenografts that had undergone optimal xenoantigen removal using α-galactosidase and PNGase-F. Additionally, this study aimed to evaluate the potential for in vivo recellularization. Methods: Decellularized porcine pericardium scaffolds treated with both enzymes were further modified by forming a fibrin mesh on their surface and within their structure, followed by the attachment of heparin and human vascular endothelial growth factor to the mesh. Subsequently, the scaffolds were seeded with human adipose tissue-derived stem cells for 8 weeks. In vitro recellularization, differentiation, and extracellular matrix remodeling of decellularized and enzyme-treated xenografts were assessed using vimentin, calponin, fibronectin, CD31, VWF, and phalloidin staining. To evaluate the potential for in vivo recellularization, decellularized glutaraldehyde-crosslinked xenografts with anticalcification treatments were seeded with rat bone marrow MSCs and implanted into rats subcutaneously to evaluate cell infiltration and calcification via histology, von Kossa staining, and micro-computed tomography. Results: In decellularized xenografts treated with both enzymes, stronger signals were detected and mesenchymal cell infiltration into the tissue was significantly faster, leading to accelerated recellularization. This recellularization process was more pronounced as time went on, with greater cell infiltration and evidence of cell differentiation. An in vivo study showed that decellularization and anticalcification treatments revealed stronger vimentin staining in histological analysis. The recellularization for our biocompatible scaffolds exhibited a lower degree of calcification compared to the non-recellularized tissue. Conclusions: We successfully developed major xenoantigen-free scaffolds by demonstrating the safety and synergistic effect of α-galactosidase and PNGase-F treatments and proved, for the first time, the effectiveness of recellularization using a human MSC monoculture on xenoantigen-free scaffolds. Furthermore, there was potential for in vivo recellularization of our biocompatible scaffolds seeded with MSCs. Full article

The limited regenerative capacity of articular cartilage (AC) following injury has led to a high prevalence of degenerative AC-related disorders, including osteoarthritis (OA). Current clinical treatments for OA have failed to halt disease progression, driving growing interest in cartilage tissue engineering (CTE) strategies aimed at developing biomimetic substitutes to regenerate damaged AC tissue. Among the available biofabrication techniques, electrospinning has gained attention due to its ability to generate fibrous scaffolds that closely mimic the architecture of the native AC extracellular matrix, while also serving as versatile drug delivery platforms with high surface area and elevated drug loading efficiency. Small molecules, low-molecular-weight therapeutic agents capable of interacting with both cell membrane and intracellular components, can be incorporated into these scaffold systems to target the underlying mechanisms of OA. This review examines the current state of the art of small molecule-loaded electrospun scaffolds for CTE applications. Small molecules targeting pain, inflammation, and cartilage function restoration show considerable therapeutic potential, and their incorporation into coaxial and other advanced electrospinning setups enables controlled and sustained drug release. Recent examples of small molecule-loaded electrospun scaffolds for AC repair demonstrate enhanced chondrogenic differentiation and neo-cartilage formation, supporting their potential as viable CTE strategies. Nevertheless, challenges related to drug release kinetics, scaffold load-bearing properties, manufacturing scalability, reproducibility, and regulatory approval remain critical barriers to clinical translation. Emerging fabrication strategies, AI-assisted optimization, personalized medicine approaches, and stimuli-responsive drug delivery systems offer promising avenues to overcome these limitations and advance the clinical adoption of these platforms. Full article

Chronic cutaneous wounds and traumatic skin injuries remain a major clinical challenge, characterized by dysregulated healing phases, high susceptibility to microbial infection, and suboptimal response to conventional therapies. Stem cell-derived exosomes (SC-Exos) have emerged as a paradigm-shifting, cell-free nanotherapeutic platform that harnesses the paracrine secretome of stem cells while avoiding the immunological and proliferative complications inherent to direct cell transplantation. Exosomes derived from diverse stem cell sources orchestrate multifactorial wound repair by modulating key cellular signaling cascades and transcriptomic programs that collectively regulate inflammation, angiogenesis, re-epithelialization, extracellular matrix (ECM) remodeling, and scar formation. Beyond their intrinsic regenerative capacity, SC Exos can be engineered using direct strategies (cargo loading, surface modification, biomaterial integration, and conjugation) and indirect approaches (genetic engineering, pretreatment, and preconditioning of parental cells), thereby enabling spatially controlled and temporally sustained exosome release at wound sites with enhanced bioavailability and therapeutic efficacy. In parallel, biomaterial-assisted delivery platforms, including hydrogels, scaffolds, and nanofibers, enhance exosome retention, stability, and controlled-release profiles within the wound microenvironment, thereby further potentiating tissue repair. This review provides a comprehensive overview of recent advances in SC Exos for wound healing and skin regeneration. We first summarize exosome biogenesis, molecular composition, and the distinctive characteristics of exosomes derived from different stem cell sources, along with preclinical evidence supporting their efficacy in cutaneous repair. We then critically examine exosome engineering strategies and biomaterial-integrated delivery systems that augment and fine-tune therapeutic outcomes. Finally, we discuss the current status of clinical trials of SC Exo-based therapies, key manufacturing and regulatory challenges, and future directions for translating these nanoscale, cell-free therapeutics into advanced, personalized wound management. Full article

Chronic wounds are frequently complicated by biofilm-associated infections that impair healing and limit treatment efficacy. Buddleja globosa (BG) exhibits antimicrobial and regenerative properties, making it a promising candidate for advanced wound care. This study aimed to optimize the concentration of a standardized BG extract incorporated into polymeric scaffolds for the treatment of wounds infected with the dual-species biofilm (DSB) of Pseudomonas aeruginosa and Staphylococcus aureus. Scaffolds containing increasing BG concentrations (BG1 to BG4) were fabricated by lyophilization and characterized in terms of physicochemical properties, antimicrobial activity, and cytocompatibility. Their therapeutic efficacy was further evaluated using an in vitro artificial wound model and a murine model of a DSB-infected wound. BG incorporation significantly influenced the scaffold properties. While BG1–BG3 maintained a comparable structure and mechanical integrity, BG4 exhibited a reduced pore size, swelling capacity, and mechanical resistance. All BG-loaded scaffolds reduced bacterial viability in vitro, with BG4 showing the strongest antimicrobial effect. In vivo, BG2 showed the most consistent overall performance, combining improved wound closure at day 6 with complete re-epithelialization at the endpoint. BG3 improved wound closure at day 6 but did not outperform it in re-epithelialization. In contrast, BG4 did not enhance healing despite its higher antimicrobial activity in vitro. These findings demonstrate that scaffold performance is governed by the interplay between extract loading and physicochemical properties, and that intermediate BG concentrations provide more favorable conditions for tissue repair than higher loadings. This work supports the potential of BG-loaded scaffolds as a therapeutic strategy for biofilm-infected chronic wounds. Full article

Biomaterials play a central role in tissue engineering and regeneration by providing scaffolds that support cell adhesion, proliferation and differentiation while modulating the surrounding microenvironment. They represent promising alternatives to traditional surgical approaches that may lead to complications or tissue damage, and their performance is influenced by chemical composition, mechanical behavior, architecture and interfacial properties, all of which can be precisely tuned through advanced fabrication and surface modification strategies. This review synthesizes evidence from a comprehensive literature search across major scientific databases, focusing on highly cited studies and available clinical data, and examines natural and synthetic biomaterials, their biological responses, functional characteristics, and surface modification methods. Emphasis is placed on Cold Atmospheric Plasma (CAP), which selectively modifies the outermost nanolayer of materials, enhancing hydrophilicity, functional group density, protein adsorption and overall cell–material interactions, as well as improving drug loading capacity. The review also considers stem cell interactions with biomaterials and emerging applications of artificial intelligence (AI) for predicting performance and guiding material optimization. Overall, the analysis highlights that natural matrices provide intrinsic bioactivity, synthetic polymers offer tunable mechanics and degradation profiles, and composite systems integrate these advantages. Advances in technologies such as electrospinning and 3D/4D printing enable precise control over architecture, supporting cell colonization and vascularization. Collectively, developments in CAP treatments and AI-driven design strategies are strengthening the regenerative potential of biomaterials and advancing their clinical translation. Full article

Stress urinary incontinence (SUI) affects a significant proportion of women and often requires surgical intervention when conservative treatments fail. While midurethral slings (MUS) are widely used, concerns over complications such as mesh exposure/erosion and chronic pain have driven interest in regenerative medicine alternatives. This review explores emerging strategies, including stem cell therapies, platelet-rich plasma injections, decellularized extracellular matrix scaffolds, injectable hydrogels, and bioengineered slings. These approaches aim to restore continence by promoting tissue regeneration, improving biocompatibility, and reducing adverse reactions. We evaluate their mechanisms, reported outcomes, and current stage of development, supported by in vitro and in vivo model data. Although promising, these technologies face challenges related to cell viability, scaffold integration, and clinical translation. Continued interdisciplinary research is essential to optimize these therapies and bring safer, more effective solutions to patients. Regenerative strategies may ultimately redefine the future of SUI treatment by offering biologically integrated, long-lasting alternatives to synthetic slings. To date, no tissue-engineered or regenerative biomimetic sling has received regulatory approval for routine clinical use in the management of stress urinary incontinence. Full article

Bone tissue has a remarkable regenerative capacity; however, advanced strategies are needed to support the repair process for critical-sized defects. While autografts and allografts remain the gold standard, their limitations have stimulated alternative approaches in bone tissue engineering, in search of scaffolds capable of mimicking native bone properties to promote effective regeneration. In this study, silk fibroin (SF)-based composite scaffolds incorporating β-tricalcium phosphate (β-TCP) and poly-ε-caprolactone (PCL) were synthesized using a simple and innovative cryogenic foaming method. The proposed fabrication technique overcomes many limitations of current synthesis methods, such as long processing times, the use of solvents, and reliance on complex, energy-intensive equipment. The composites were characterized using infrared spectroscopy to confirm the incorporation of all three components and their chemical bond arrangements. µ-CT, SEM, and ESEM analyses revealed that SF/β-TCP/PCL scaffolds exhibited great porosity and dynamic interaction with water while preserving pore morphology in wet environments. Swelling behavior, indirect cytotoxicity, and cell proliferation tests recognized the greater performance of SF/β-TCP/PCL scaffolds in promoting long-term cell proliferation, maintaining superior mechanical properties. These findings indicate that the proposed original, simple, and relatively low-cost manufacturing approach enabled the fabrication of scaffolds with excellent mechanical performances, controlled and stable porosity under both dry and physiological-like conditions, and high biocompatibility. The resulting constructs demonstrated promising results for cell proliferation and osteoconductive behavior, supporting their potential suitability as artificial bone substitutes. Full article