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Challenges and future directions in AI-driven biomaterials for microbiome-associated oral infectious diseases: A systematic review.

Oral biofilm-induced antimicrobial resistance is the core pathogenic mechanism of microbiome-associated oral infectious diseases (dental caries, periodontitis, peri-implantitis, and endodontic infection). Traditional therapies and biomaterials are limited by poor biofilm penetration, drug resistance induction, single functionality, and inadequate adaptation to dynamic oral microenvironmental changes (e.g., pH fluctuations, salivary rinsing, masticatory stimulation). Artificial intelligence (AI) has transformed the field by integrating materials science, microbiology, and stomatology data. Via machine learning, deep learning, and multi-physics simulation, AI optimizes biomaterial physicochemical properties, decodes microenvironmental signals, constructs precise sensing-response loops, and supports the full chain of material design, performance prediction, and action simulation, advancing treatment from empirical intervention to precision regulation. This systematic review retrieved literature from PubMed, Embase, and Web of Science (January 2016-January 2026) using keywords across three dimensions: AI, biomaterials, and oral microbiome. Following inclusion/exclusion criteria, 99 articles were included. It elaborates on five core mechanisms of AI-driven oral biomaterials (precise oral microbiome analysis, targeted material design/optimization, performance prediction/simulation, targeted delivery/intervention, effect evaluation/dynamic regulation), analyzes their applications in microbiome-targeted biomaterial research and development (R&D) and clinical practice for the four major oral infectious diseases, addresses technical bottlenecks (insufficient targeting specificity and precision of biomaterials, poor stability and durability in complex oral microenvironments, inadequate biofilm disruption capacity, and clinical translation obstacles), and proposes future directions (multimodal design to enhance targeting specificity, structural and component optimization to improve stability/durability, development of multi-mechanism synergistic biofilm disruption strategies, strengthening translational research for clinical application, and deep integration of AI in the full chain of biomaterial R&D). This work provides comprehensive theoretical and practical support for the R&D, optimization, and clinical translation of AI-driven microbiome-targeted oral biomaterials.

Humans

Biomaterial-Integrated Electroporation for Therapeutic Delivery: From Gene Editing to Tumor Ablation and Immune Modulation.

Electroporation has evolved from a membrane-permeabilization method into a versatile therapeutic platform for intracellular delivery, locoregional tumor intervention, and bioelectrically regulated treatment. Depending on pulse intensity and duration, electroporation operates in two distinct modes: reversible electroporation (RE), which transiently permeabilizes the plasma membrane to enable delivery of nucleic acids, proteins, and small molecules while preserving cell viability, and irreversible electroporation (IRE), which causes permanent membrane damage for non-thermal tissue ablation. Increasingly, the therapeutic scope of electroporation is being expanded through integration with biomaterials, including nanocarriers, hydrogels, soft conductors, and micro/nanoengineered bioelectronic interfaces. These material-assisted strategies improve cargo protection, field confinement, local retention, tissue conformity, and spatiotemporal control, thereby extending electroporation beyond conventional transfection toward gene editing, engineered cell manufacturing, electrochemotherapy, tumor ablation, immune modulation, and transdermal or localized delivery. In this Review, we summarize the biophysical principles of RE and IRE, discuss how biomaterials reshape electroporation performance across therapeutic settings, compare the design logic of major biomaterial-assisted electroporation platforms, and highlight key translational challenges, including pulse-material compatibility, manufacturing scalability, in vivo dosimetry, and regulatory complexity.

Humans

Seed-derived mucilage polysaccharides as biomaterials for in vivo tissue regeneration: A systematic review.

Chronic wounds, bone defects, and cartilage injuries represent persistent clinical challenges requiring biomaterial platforms that actively regulate inflammation, oxidative stress, angiogenesis, and extracellular matrix remodeling. Conventional synthetic dressings often provide limited biological activity in these contexts. Seed-derived mucilages - polysaccharide-rich hydrocolloids obtained from chia (Salvia hispanica), flaxseed (Linum usitatissimum), fenugreek (Trigonella foenum-graecum), psyllium (Plantago ovata), guar (Cyamopsis tetragonoloba), quince (Cydonia oblonga) etc. - have emerged as biocompatible, biodegradable, and chemically versatile platforms for tissue engineering. This systematic review, conducted according to PRISMA 2020 guidelines, synthesized in vivo evidence on seed-derived mucilage-based biomaterials across wound healing, bone repair, cartilage regeneration, and related applications. PubMed, Scopus, and Web of Science Core Collection were searched for original in vivo experimental studies published in English between 2020 and 2026. Eligible studies reported at least one measurable regenerative outcome. Data were extracted independently by two reviewers, and methodological quality was assessed using the SYRCLE Risk of Bias tool. Forty-three studies were included. Hydrogels were the dominant biomaterial format, followed by films, scaffolds, sponges, nanoparticle systems, and bilayer or Janus composites. Included systems generally improved wound closure, re-epithelialization, collagen deposition, angiogenesis, antioxidant defense, and inflammatory regulation. However, most studies used small animals with short follow-up periods, and many incorporated nanoparticles or bioactive agents, limiting attribution of efficacy to the mucilage matrix alone. Risk of bias was predominantly unclear due to insufficient reporting of randomization and blinding. Blank mucilage controls, standardized characterization, long-term biosafety data, and clinically relevant models are essential prerequisites for translational progress.

Humans

Future developments and applications of biomaterials: an overview.

It is recommended that the emphasis of biomaterials research and development for the future should be to achieve improved reliability. Use of increasing numbers of implants per year coupled with decreasing long term (greater than 5 years) success rates are resulting in progressively larger numbers of reparative implant operations. This trend can be altered by emphasizing three areas of R&D: 1) Studies of composite biomaterial systems offering unique combinations of biological surface behavior and substrate mechanical performance; 2) Investigate mechanisms of interfacial reactions so that long term responses of the host-implant can be predicted; 3) Develop long term predictive relationships for biomaterials reliability based upon interfacial reactions, biomechanics, fracture mechanics, fatigue testing, and retrieval analysis. Brief examples of efforts to develop undrestanding in these three areas are described using bioglass coated metal and bioglass coated alumina implants.

Alloys

Perspective and trends for biomaterials.

Biomaterials may be synthetic or of natural origin used in contact with living tissue and biological fluids for prosthetic, diagnostic, therapeutic, and storage applications. The opposing phenomena of clotting and fibrinolysis under physiological conditions significantly influence the biocompatibility of materials. Although smooth-surfaced biomaterials adsorb proteins when in contact with blood, subsequent enzymatic and hemorheological events alter these proteins, thus influencing their biological performance. In contrast to synthetic materials, the healthy, living endothelium exhibits active secretory functions in the maintenance of blood compatibility. The increasingly wide use of biomaterials besides cardiovascular surgery justifies a broad-based approach because too narrow objectives often bypass significant opportunities that are realistic in terms of technological advancement and societal needs.

Animals

Current status of biomaterial's clinical applications in plastic and reconstructive surgery.

The use of biomaterials as replacement parts is not new. The concept has fascinated physicians for thousands of years. Using gold plates to reconstruct defects in the skull over 3000 years ago constituted the early record in the literature of use of biomaterials in implantology. The recent advances in space age technology and in clinical biocompatibility has been a major contributing factor in introducing new materials for use as implantology polymers. However, the ideal implant is still not there, and whenever a major reconstruction is required consideration should be given first to the use of autogenous substitutes; when that is not available, then we should resort to inorganic substitutes.

Abdominal Muscles

Uniform microporous biomaterials prepared by the Relamineform technique.

The Replamineform process provides a technique for fabricating microporous ceramic, metal and polymer biomedical implant materials. A range of pore sizes can be made in the same material, thus allowing independent study of the effect of pore size and biomaterial on incorporation of implants. This new family of biomaterials shows promise for helping to determine the optimum characteristics to enhance tissue regeneration.

Aluminum Oxide

Oxygen-controlled gamma-irradiation and annealing enable terminal processing of collagen-based biomaterials.

Gamma irradiation is a widely adopted method for terminal sterilization of medical devices; however, its application to collagen-based extracellular matrix (ECM) materials remains limited due to radiation-induced degradation of structural integrity and mechanical performance. Here, we present an engineered terminal-processing strategy that combines oxygen controlled gamma irradiation (25-30 kGy) with post-irradiation dry-heat annealing to preserve ECM functionality while achieving effective sterilization. By modulating oxygen availability during irradiation, this approach alters radical reaction pathways, suppresses oxygen-mediated oxidative degradation, and generates a metastable radical-containing intermediate, which is subsequently converted into a structurally stabilized collagen network through thermal annealing. As a result, the treated matrices preserved ECM integrity and recovered clinically relevant mechanical properties. Furthermore, the process achieved cumulative viral reductions exceeding 6 log10 across a representative panel including enveloped and non-enveloped DNA and RNA viruses, demonstrating compatibility with sterility assurance and viral safety requirements for biologically derived medical devices. Notably, preliminary observations indicate that mechanical integrity can be partially preserved even at elevated irradiation doses up to 50 kGy, suggesting potential applicability to sterilization validation frameworks requiring higher assurance levels. Overall, this work establishes a mechanistically grounded terminal-processing paradigm that enables control of radical fate, decouples sterilization efficacy from material degradation, and integrates sterilization, viral safety, and functional preservation into a unified and scalable framework for collagen-based biomaterials. This concept repositions gamma-irradiation from a purely degradative process to a controllable tool for tuning collagen structure and performance.

Gamma Rays

Biomaterials and collagen synthesis.

A highly reactive biomaterial (clay) and a relatively nonreactive substance (silicone) were implanted separately in primarily closed incisions on the backs of rats. Collagen synthesis was determined in biopsies from each test site after 8 days. The biochemical measurements of collagen synthesis showed a significant correlation with the gross pathologic and histologic findings.

Animals

A method for evaluation of initial tissue response to biomaterials.

In the present paper an implantation technique is described whereby the effect of the surgical operation is eliminated and initial tissue reactions to materials may be studied. A teflon body was implanted intramuscularly in rabbits. After six weeks the overlaying tissue was excised and the implant removed. An intact, nonepithelialized tissue surface was exposed, which due to the shape of the implant showed three indentations. Materials were placed in the indentations for 15 minutes and the tissue reaction was registered by enzyme histochemical methods. Silicate cement, zinc phosphate cement and a 4% phenol solution caused an inhibition in the dehydrogenase enzyme activity in the tissue subjacent to the indentations. The severity of the tissue reaction, indicated by the width of the inhibition zone, varied among the test materials. Silicate cement caused the widest inhibition zone and the phenol solution the narrowest one. These results correlate well with previous tissue compatibility studies and indicate that the method is applicable for in vivo screening of initial tissue response to biomaterials.

Animals

Considerations of species-related hematological differences on the evaluation of biomaterials.

Species-related hematological differences of experimental animals are important in the proper assessment of biomaterials intended for human use. This area, which has received less than adequate attention in the past, requires the development of new test methodologies with blood of primates and humans, under conditions that better simulate the physiological environment.

Animals

Engineering criteria for biomaterials: some thought on in situ measurements.

Several non-destructive techniques now exist which show promise of providing information about implant performance in situ. Surface wave ultrasonics have been used successfully in the laboratory to measure the anisotropic properties of bone. It has also been used clinically to assess rates of fracture healing. Acoustic emission has been used experimentally to investigate bone abnormalities such as microfracture and osteoporosis in vitro. Application of these techniques to clinical studies depends upon the establishment of the appropriate parameters for bone and the various biomaterials used as implants. Surface wave ultrasound may also provide information about tissue ingrowth into porous systems. Acoustic emission can be especially significant in the early detection of implant failure.

Acoustics

Soft tissue response to four dense ceramic materials and two clinically used biomaterials.

Disk-shaped implants of spinel, alumina, mullite, zircon, a cast Co-Cr-Mo alloy, and ultra-high molecular weight polyethylene (UHMWPE), were implanted in the paraspinalis muscle of 12 adult, male, white New Zealand rabbits. Prior to implantation the implants were characterized with respect to size and shape, weight and surface roughness. After periods of 1 month, 2 months, and 4 months, the rabbits were sacrificed and the tissue specimens were retrieved with the implants still intact. Histological examination of the tissues surrounding the implants along with changes in the size and shape, weight, and surface roughness of the implants were used as criteria for evaluating these materials for implant purposes. No surfaces degradation of any of the materials was detected using scanning electron microscopy. Fibrous tissue seemed to adhere to the UHMWPE implants more than any other material used in this study. Large amounts of fibrous tissue were also found to adhere to the cast Co-Cr-Mo alloy implants. The histological results indicated that within the limits of this investigation, the biocompatibility of the ceramic materials used in this study compared favorably with the clinically used Co-Cr-Mo alloy implants and the UHMWPE implants.

Aluminum

The restoration of the articular surfaces overlying Replamineform porous biomaterials.

Replamineform porous implants (4 mm X 4 mm diameter) were placed into full-thickness cartilage and bone defects of the weight-bearing surface of the lateral femoral condyles of adult male white rabbits. These were analyzed at 1 day, 1 week, 6 weeks, 3 months, and 6 months for 1) ingrowth of tissue within the implants and 2) restoration of the articular surface overlying them. Appropriate unfilled, but similar, control defects were also studied. Mineralized bone was seen within the substance of both the TiO2 and hydroxyapatite implants at 1 week; this extremely rapid response was present in every specimen studied and was not seen with alphaAl2O3 or control animals. With the passage of time, maturation of this bone ingrowth occurred so that by 3 months, they were all incorporated into the surrounding bone. Only the hydroxyapatite implants showed consistent regenerative healing of hyaline articular cartilage from the margins of the defects with the passage of time; this occurred whenever the subchondral bone adjacent to the defect proliferated in a "creeping" fashion over the articular aspect of the implant, and the undamaged cartilage then followed it. Fibrocartilage, and not hyaline cartilage, formed the articular surface over the TiO2 and alphaAl2O3 implants and in the controls.

Aluminum

A method for toxicity screening of biomaterials using cells cultured on millipore filters.

In the present paper a tissue culture technique is described whereby the toxicity of setting and solid materials may be evaluated. A cell monolayer was established on a millipore filter which was placed on an agar medium, cell side down. Test specimens were placed on top of the millipore filter and were allowed to influence the cells through the filter for two hours. The cell reaction was assessed by incubating the cells, still adherent to the filter, for the demonstration of succinate dehydrogenase activity. Materials with a cytotoxic effect caused a zone of inhibited enzyme activity in the cell-material contact area. The filters were examined macroscopically and scores from 0 to 3 were given to grade the severity of the cell response. Unset and set silicate cement, zinc phosphate cement and an acrylic resin were tested. The results obtained were consistent and in accordance with those of previous reports. The method was simple and rapid and appeared suitable for the assay of larger test series.

Animals

Transient in vivo protein adsorption onto polymeric biomaterials.

The adsorption of albumin, gamma-globulin, and fibrinogen was measured on three ex vivo polymeric shunt surfaces [polyvinyl chloride (PVC), Silastic, and segmented polyether urethane (Biomer)] exposed to flowing heparinized, canine blood in vivo. Small amounts of radiolabeled proteins were infused into anesthetized mongrel dogs and the deposition of radioactivity on the walls of femoral arteriovenous shunts was followed with time for two hours following initial blood-polymer contact. Previously, transient in vivo platelet and fibrin deposition onto PVC, Silastic, and Biomer was measured by a similar technique in the absence of anticoagulant. A time-dependent phase of thrombus deposition followed by thromboembolism was observed on the PVC and Silastic shunt surfaces but not on the Biomer surface. In the studies reported here on PVC and Silastic, fibrinogen adsorption was found to predominate initially, though it subsequently desorbed somewhat and was replaced by albumin and gamma-globulin. On Biomer, the adsorption of all three proteins increased with time following initial blood contact and fibrinogen was less prominent initially. The PVC surface was found to become passivated with respect to further thrombogenesis after 60-min exposure to flowing blood, at which time a higher fraction of albumin was present on the surface compared to that at earlier blood contact times. These results indicate that rearrangement of adsorbed protein species occurs with time on polymer surfaces exposed to flowing blood in vivo. Early and predominant fibrinogen adsorption appears to be an important factor in the thrombogenic and embolic events observed on the PVC and Silastic shunt surfaces in vivo.

Adsorption

SEM fractography studies of porous vitreous carbon: a candidate biomaterial.

A new porous vitreous carbon material under development for use in orthopedic applications was investigated. Specimens were machined to appropriate sizes and fractured in one of the following modes: compression, cantilevered bending, or axial torsion. Scanning electron microscopy (SEM) was used to examine surface and internal features. Characteristics of a brittle, glassy material were noted. Findings included internal voids which appeared as craters, patches of whiskerlike fibrils, and edge impurities. Numerous microcracks caused by mechanical shaping and handling were the most remarkable structural defects. Pore channels which would allow bony ingrowth ranged in size from 50--500 micrometers with the majority between 200 and 300 micrometers. This study of porous vitreous carbon points to the need for stricter quality control in manufacturing, alternative methods for shaping and handling, and careful consideration in design and usage of a brittle material with marginal limits of safety for biomedical applications.

Biocompatible Materials

Degradation resistance of some candidate composite biomaterials.

The degradation resistance of matrix, fiber and composite systems which we have been studying as candidate orthopedic materials has been examined in two appropriate environments. Both resistance to steam sterilization in an autoclave environment and resistance to a simulated physiologic solution have been studied. In the autoclave study, samples were placed in a pressure cooker at 123 degrees C for differing amounts of time and tested for retention of mechanical properties. Results indicate that most of the materials tested could be autoclaved several times, as long as autoclave times did not exceed 1 hr. Longer autoclave times result in an accelerated degradation and loss of strength of all materials except the polypropylene. Polysulfone degrades after even the shortest autoclave duration. Resistance to the simulated physiologic environment was tested by measured retention of mechanical properties after immersion times in pseudo-extracellular fluid (PECF) at 37 degrees C for as long as three years. None of the materials showed any significant changes in properties after immersion in the PECF.

Amides