Journal of Functional Biomaterials最新文献

Ex vivo human tooth culture models preserve the native dentine-pulp complex and offer a translational platform to study pulp-capping biomaterials. This systematic review aimed to synthesize the evidence on histological pulp tissue responses to calcium silicate-based cement (CSCs) used for direct pulp capping in human tooth culture models. The review followed PRISMA 2020 guidance. Eligible studies were ex vivo whole human tooth culture models with direct pulp exposure treated with commercial or experimental CSCs and reporting histological outcomes. Risk of bias was assessed using the QUIN tool. Thirteen studies were included. Most used immature human third molars (from 15- to 19-year-old patients) and culture periods up to 28 days, with a minority extending observation to 45-90 days. Across hydraulic CSCs, Biodentine was the most frequently evaluated material, followed by ProRoot MTA and several experimental hydraulic and resin-modified formulations. Overall, hydraulic CSCs were consistently associated with biocompatible pulp responses and a pro-mineralization pattern characterized by periexposure mineralized foci/osteodentin-like tissue; where assessed, immunohistochemistry supported odontoblast-like differentiation. In contrast, the resin-modified CSC TheraCal LC and other experimental resin-modified CSCs showed more heterogeneous findings, with reports of absent, delayed, or less prominent mineralization compared with reference hydraulic CSCs. In intact human tooth culture models, hydraulic CSCs show reproducible biocompatibility and early mineralization features consistent with reparative dentinogenesis, whereas resin-modified CSCs demonstrate more variable histological performance.

Background: Autogenous tooth-derived grafts have been proposed as an alternative to xenografts for alveolar ridge preservation, offering biological similarity to bone and potentially more favorable remodeling. This study compared the healing outcomes of a collagenated xenograft, and a tooth-derived graft prepared with an automated processing device.

Methods: Six Beagle dogs underwent bilateral extraction of the third and fourth mandibular premolars. Each animal contributed two sockets grafted with root-derived particulate prepared using an automated device for tooth cleaning, grinding, and demineralization, and two sockets grafted with a collagenated xenograft, all covered by a collagen membrane. After 3 months, histological sections were analyzed to assess crestal dimensions and the relative proportions of mature (lamellar) and immature bone (woven/parallel fibered), residual graft material, and soft tissues.

Results: Lingual crest height did not differ between groups, whereas the buccal crest was slightly higher at xenograft sites compared with the tooth-graft sites. The tooth-graft group exhibited significantly fewer residual particles (0.5 ± 1.1%) and a higher proportion of total bone (65.6 ± 9.1%) compared with the xenograft group, which showed 19.7 ± 16.0% graft remnants (p = 0.032). Corticalization at the socket entrance was observed predominantly in the tooth-graft sites. No inflammatory infiltrates were detected in the examined section.

Conclusions: Tooth-derived grafts promoted an almost complete replacement by vital bone with minimal residual material, whereas xenografts provided slightly better buccal contour preservation but resulted in regenerated tissues containing persistent graft particles. The biological differences observed may have implications for subsequent implant placement.

Large bone defects resulting from trauma, tumor resection, congenital anomalies, infection, or revision surgery represent a persistent and unresolved challenge in orthopedic, maxillofacial, and reconstructive surgery [...].

Background: Autologous arteriovenous fistula (AVF) is the most commonly used vascular access for end-stage renal disease patients. However, during the maturation process following AVF surgery, insufficient initial venous diameter often results in inadequate blood flow, leading to fistula maturation failure. Studies have indicated that implanting stents can enlarge the initial venous diameter and improve the success rate of AVF surgeries. However, stents made from metallic materials remain permanently in the body after implantation, posing risks such as in-stent restenosis.

Methods: Our development and testing of magnesium alloy stents with a layered double hydroxide (LDH) coating to assist AVF maturation is presented in this paper. Firstly, AZ31 alloy was used as a benchmark to screen coating technologies, including anodizing, alkaline films, and LDH coatings. ZM21 tubes were then utilized to verify the transferability of optimized parameters across different substrates. Finally, the optimized coating was applied to ZM21 stents, followed by validation through in vitro degradation tests and biochemical simulations.

Results: The results showed that LDH-coated AZ31 samples exhibited a 95% reduction in average corrosion rate compared to untreated samples. Additionally, the anion exchange property of the LDH layer effectively reduced the pH of the saline solution. Subsequently, LDH coatings were applied to ZM21 magnesium alloy stents, followed by in vitro degradation and biochemical simulation. Compared to untreated ZM21 stents, LDH-coated stents demonstrated a 94.9% reduction in average corrosion rate and significantly reduced the generation of soluble magnesium chloride, maintaining the solution pH below 8.0 and the Mg²⁺ concentration below 300 μg/mL.

Conclusions: The results show LDH is the most effective corrosion-resistant coating and can control the degradation rate of magnesium alloy stents to enhance their support duration and biocompatibility.

This review synthetizes experimental evidence on collagen-related bioactivity and the biomaterial potential of plant species native to the Chihuahuan Desert, aiming to identify natural compounds that could enhance next-generation dermal bioinks for 3D bioprinting. A structured search across major databases included studies characterizing plant extracts or metabolites, with reported effects on collagen synthesis, fibroblast activity, inflammation, oxidative balance, or interactions with polymers commonly used in skin-engineering materials being developed. Evidence was organized thematically to reveal mechanistic patterns despite methodological heterogeneity. Several species, among them Larrea tridentata, Opuntia spp., Aloe spp., Matricaria chamomilla, Simmondsia chinensis, Prosopis glandulosa, and Artemisia ludoviciana, repeatedly demonstrated the presence of bioactive metabolites such as lignans, flavonoids, phenolic acids, terpenoids, and polysaccharides. These compounds support pathways central to extracellular matrix repair, including stimulation of fibroblast migration and collagen I/III expression, modulation of inflammatory cascades, antioxidant protection, and stabilization of ECM structures. Notably, several metabolites also influence viscoelastic and crosslinking behaviors, suggesting that they may enhance the printability, mechanical stability, and cell-supportive properties of collagen-, GelMA-, and hyaluronic acid-based bioinks. The review also reflects on the bioethical and sustainability considerations regarding endemic floral resources, highlighting the importance of responsible sourcing, conservation extraction practices, and alignment with international biodiversity and access to benefit/sharing frameworks. Taken together, these findings point to a promising, yet largely unexplored, opportunity: integrating regionally derived phytochemicals into bioinks to create biologically active, environmentally conscious, and clinically relevant materials capable of improving collagen remodeling and regenerative outcomes in 3D-printed skin.

Chronic liver disease remains a leading cause of global mortality, yet organ shortages and transplant complications limit the efficacy of orthotopic liver transplantation. While extracorporeal support systems serve as temporary bridges, they fail to restore long-term patient autonomy or replicate complex biosynthetic functions. This systematic review, conducted in accordance with PRISMA 2020 guidelines, evaluates recent advancements in implantable artificial livers (IALs) designed for permanent functional integration. We analyzed 71 eligible studies, assessing cellular sources, fabrication strategies, maturation processes, and functional readiness. Our findings indicate significant progress in stem-cell-derived hepatocytes and bioactive scaffolds, such as decellularized extracellular matrix (dECM). However, a critical technological gap remains in scaling current sub-centimeter prototypes toward clinically relevant volumes (~200 mL). Key engineering challenges include integrating hierarchical vascular networks, requiring primary vessels exceeding 2 mm in diameter for surgical anastomosis, and functional biliary systems to prevent cholestatic injury. Furthermore, while micro-vascularization and protein synthesis are well documented, higher-order functions such as spatial zonation and coordinated metabolic stability remain underreported. Future clinical translation necessitates advancements in multi-cellular patterning, microfluidic-driven maturation, and autologous reprogramming. This review provides a comprehensive roadmap for bridging the gap between biofabricated constructs and organ-scale hepatic replacement, emphasizing the need for standardized functional benchmarks to ensure long-term success.

4D printing, as an advanced evolution of 3D bioprinting, introduces time as an active design dimension, enabling printed constructs to undergo programmed morphological or functional transformations in response to external or endogenous stimuli. By integrating stimuli-responsive smart materials with precise additive manufacturing, 4D printing provides a bio-inspired strategy to overcome the inherent limitations of static scaffolds and to achieve spatiotemporal dynamic matching with the evolving biological microenvironment during tissue regeneration. Over the past decade, significant progress has been made in applying 4D printing to structurally and functionally complex tissues, including bone, muscle, vasculature, nerve repair, wound closure, and other emerging biomedical scenarios. Rather than emphasizing shape change alone, recent advances demonstrate that 4D-printed constructs can emulate key biological processes such as morphogenesis, contraction, directional guidance, electrophysiological signaling, and microenvironment-responsive regulation, thereby enhancing tissue integration and functional recovery. This review systematically summarizes materials, stimulus-response mechanisms, and representative applications of 4D printing from a bio-inspired perspective, while critically discussing current challenges related to material performance, mechanistic understanding, manufacturing precision, and clinical translation. Finally, future perspectives are outlined, highlighting the importance of interdisciplinary integration, intelligent manufacturing, and clinically oriented evaluation frameworks to advance 4D printing toward personalized and precision regenerative medicine.

Skin aging could lead to dermal collagen loss and elastic fiber degradation, ultimately manifesting as skin laxity. We aimed to counteract this by using poly-L-lactic acid (PLLA) microsphere (MS)-based fillers to facilitate long-term volume restoration through collagen regeneration. However, conventional MSs exhibit limitations such as broad size distribution and surface irregularities, which are frequently associated with significant adverse reactions. This study employed shirasu porous glass (SPG) membrane emulsification to fabricate uniform and well-shaped polyethylene glycol-block-poly (L-lactic acid) (PEG-PLLA) MSs. A single-factor experiment was employed to optimize the parameters. The optimal preparation conditions for PEG-PLLA MSs were as follows: PEG-PLLA concentration of 40 mg/mL, polyvinyl alcohol (PVA) concentration of 0.5%, and magnetic stirring speed of 200 rpm. Under the optimal conditions, the average particle size of PEG-PLLA MSs was 58.982 μm, and the span value (SPAN) was 1.367. In addition, a cytotoxicity assay was performed, and the results revealed no significant toxicity of the MSs toward L929 mouse fibroblasts at concentrations below 500 μg/mL. Furthermore, PEG-PLLA MSs significantly enhanced the production of key extracellular matrix (ECM) components-type I collagen (Col-I), type III collagen (Col-III), and hyaluronic acid (HA)-while simultaneously alleviating cellular oxidative stress responses. This work offers a reliable and reproducible fabrication strategy for developing biocompatible MS fillers with controllable particle sizes.

Background: This in vitro study aimed to evaluate the effect of microabrasion as a surface pretreatment and to compare an experimental resin infiltrant with a commercially available system (ICON) in terms of enamel surface microhardness recovery and resin penetration depth in artificially demineralized enamel lesions. Methods: Forty-eight caries-free human third molars were prepared to obtain standardized enamel specimens, and artificial enamel lesions were created using a pH-cycling model. Specimens were randomly allocated into four groups (n = 12): experimental resin with microabrasion, experimental resin without microabrasion, ICON resin with microabrasion, and ICON resin without microabrasion. When indicated, microabrasion was performed using a 6.6% hydrochloric acid paste for a total application time of 30 s, followed by standard hydrochloric acid etching as part of the infiltration protocol. Enamel surface microhardness was measured at baseline, after demineralization, and after resin infiltration. Resin penetration depth was assessed using confocal laser scanning microscopy, with six specimens per group (n = 6). Data were analyzed using repeated-measures mixed-effects models and one-way ANOVA (p < 0.05). Results: Resin infiltration resulted in a partial recovery of enamel surface microhardness following demineralization; however, baseline hardness values were not fully restored, and no statistically significant differences were observed among the study groups (p > 0.05). These findings indicate surface stabilization rather than complete mechanical or mineral restoration. The ICON resin demonstrated significantly greater penetration depth than the experimental resin. In both resin systems, microabrasion significantly increased penetration depth. Conclusions: Within the limitations of this in vitro study, resin infiltration primarily contributed to the stabilization of demineralized enamel surfaces rather than true remineralization or full mechanical recovery. Although microabrasion enhanced resin penetration depth, this effect should be interpreted with caution due to the potential for cumulative enamel loss. From a clinical perspective, these findings support the selective use of microabrasion to enhance resin infiltration in early enamel lesions with pronounced surface barriers, while emphasizing the need to balance penetration benefits against enamel preservation.

This study investigates the effect of three-dimensional (3D) bioprinted collagen (Col) scaffolds (2% w/v collagen) loaded with autologous bone marrow stromal cells (BMSCs) and enriched with bone morphogenetic protein-2 (BMP-2) and hydroxyapatite-based particles (HAPPs) on bone regeneration in calvarial defects in rabbits. Three implant formulations, Col-(BMP-2) (at a concentration of 80 ng/mL), Col-HAPP (1% w/v) and a mixture of the two-Col-(BMP-2)-HAPP (40 ng/mL final concentration and 0.5% HAPP), were compared with a control group C-Per containing only periosteum to assess the influence of material structure, biochemical signals and cell component on osteogenesis. Histological analysis and quantitative computed tomography (CT) imaging parameters (HU values and residual defect diameter) showed significant differences between the groups, highlighting the role of combined strategies for optimal bone repair. The control group demonstrated the weakest regeneration, expressed by minimal lamellar bone and the largest residual defect. Col-(BMP-2) stimulated moderate osteoinduction with active osteoblasts but without a fully organised lamellar structure. Col-HAΡΡ provided more advanced regeneration, with histologically observed thick osteoid lamellae, early calcification, and structured lamellar architecture, emphasising the osteoconductive role of HAΡΡs. The strongest regeneration was reported with Col-(BMP-2)-HAΡΡ, where the synergy between BMP-2, HAΡΡs and BMSCs resulted in formed osteons, well-developed cancellous bone and minimal residual defects. The established negative correlation between bone density and residual calvarial defects emphasises the relationship between mineralisation and the degree of defect filling. The new data presented demonstrate that the combination of the abovementioned structural, biochemical and cellular factors in 3D bioprinted scaffolds offers a promising strategy for osteoregeneration of complex bone defects.