Search Results (170)

Programmable peptide hydrogels represent advanced supramolecular biomaterials featured with customizable molecular sequences and tunable self-assembly behaviors, which can biomimetically reconstruct the structural and microenvironmental complexity of native extracellular matrix. This review systematically elaborates the molecular engineering advances of programmable peptide hydrogels following a hierarchical logic from fundamental mechanisms to translational applications. We first interpret the intrinsic self-assembly mechanisms driven by non-covalent interactions and the regulatory effects of typical external microenvironmental stimuli. On this basis, we summarize core rational design principles, covering stimuli-responsive structural optimization, biofunctional modification, and the tunable regulation of physical properties, degradability and immunogenicity. Furthermore, we correlate multi-scale structural features (nanostructures, porous architecture and mechanical properties) with their versatile biomedical functions, and comprehensively discuss their cutting-edge applications in tissue regeneration, targeted drug and gene delivery, cell-mediated therapy, immunomodulation, and anti-infective treatment. Finally, we identify critical translational barriers including batch-to-batch inconsistency, immunogenic risks, and in vivo performance instability, and highlight future directions involving multi-stimuli-responsive systems, artificial intelligence-assisted design, computational modeling, and hybrid material construction. This work systematically clarifies the structure–property–function relationship of peptide hydrogels, and underscores their great potential as next-generation platforms for precision regenerative medicine and targeted disease intervention. Full article

Hydrogels constructed from peptide components often rely on β-sheet architectures for their assembly, yet the process of developing such materials in aqueous environments presents notable hurdles in the context of biological systems. To address this, a novel functional dodecapeptide has been developed, capable of self-assembling into supra-molecular hydrogels via zinc chelation interactions. Morphological observations revealed a compact meshwork structure in the hydrogel formed with 9 mM Zn²⁺, differing from the relatively sparse or excessively tangled fiber architectures seen at other zinc concentrations. Alkaline phosphatase activity, an early marker of osteoblast differentiation, was notably enhanced when MC3T3-E1 cells were cultivated for 72 h in the hydrogel extract containing 300 μg/mL of the peptide, 9 μg/mL ZnCl₂, and 18.93 μg/mL H₃BO₃. Furthermore, increased protein levels of p-p38/p38, p-ERK/ERK, and p-JNK1/2/3/JNK1/2/3 were observed in P-300-ZnB and P-300 B hydrogel-treated groups, suggesting an association with MAPK pathway activation. P-Zn-9 hydrogel also promoted MC3T3-E1 cell proliferation and demonstrated favorable biocompatibility in short-term in vitro and in vivo assays. Long-term toxicity and causal relationships via inhibitor studies remain to be investigated. These results offer a viable approach to endow zinc-chelating properties in the fabrication of assembled hydrogels, presenting an innovative and potential method for constructing injectable drug delivery systems and in situ bone repair through biomaterials in subsequent applications. Full article

Traumatic brain injury (TBI) is a prevalent neurological disorder that induces severe neurological dysfunction and markedly reduces quality of life owing to its complex pathophysiology and limited therapeutic options. Conventional pharmacological and surgical interventions show restricted efficacy because of poor blood–brain barrier penetration and inability to address secondary injury cascades. In recent years, hydrogels have shown significant potential for TBI repair due to their superior biocompatibility, high water content, and ability to mimic the native extracellular matrix (ECM). This review systematically examines recent advances in hydrogel applications for TBI therapy, focusing on their roles as drug delivery platforms, stem cell scaffolds, neuroregeneration promoters, inflammation modulators, and angiogenesis facilitators. Particular emphasis is placed on the therapeutic benefits and underlying mechanisms of ECM-derived hydrogels, self-assembling peptide (SAP) hydrogels, stimuli-responsive smart hydrogels, and functionalized multicomponent systems. Current challenges and limitations in hydrogel applications are also discussed, along with future research directions, to provide scientific rationale and practical guidance for precision TBI therapy. Full article

The self-assembly of peptide-based building blocks into ordered structures is widely exploited for the development of novel biomaterials, including hydrogels. In this review, we analyze the effect of chirality on the ability of peptides to form hydrogels. We describe systems composed of peptides of opposite chirality i.e., peptides composed of all L- or D-amino acids and peptides composed of amino acids with alternate chirality, i.e., one L- and D-amino acid or one block containing all L-amino acid followed by one block composed of all D-amino acids. Finally, we illustrate systems composed of mixtures of L- and D-peptides. The structural features of these compounds are discussed. We further compare the mechanical properties of hydrogels formed by homochiral and heterochiral peptides. Finally, we discuss the potential biological applications of these systems, focusing on the differences between hydrogels formed from peptides of opposite chirality or mixed chirality. Full article

Peptide-based materials represent a rapidly growing field in nanotechnology, bridging bottom-up self-assembly and top-down approaches for the development of functional nanostructures. Among these systems, peptide-based nanogels (NGs), namely nanogels in which peptides assume a structural role, have emerged as a promising class of injectable formulations. Typically characterized by a core–shell architecture, these systems are closely related to peptide hydrogels in terms of structural organization. This review provides a state-of-the-art overview of peptides used as core structural elements for NG formulation, focusing on the peptide building blocks employed, the main formulation methodologies, and their current applications, with particular emphasis on pharmaceutical ones. Their potential as drug delivery systems and stimuli-responsive platforms for controlled and targeted release is also reported. For clarity, the reported formulations are classified according to the chemical nature of the core-structuration peptide, distinguishing systems based on Fmoc-FF from those derived from other primary sequences, including Boc-protected tripeptides, dehydropeptides, and chemically crosslinked peptide assemblies. Full article

Peptide-based supramolecular hydrogels have emerged as promising biomaterials due to inherent biocompatibility, tunable self-assembly, and structural similarity to the extracellular matrix. This work describes the design, synthesis and characterization of a library of symmetrical bolaamphiphiles based on dehydropeptides, systematically varying both the dehydroamino acid residue and the linker. Aromatic and aliphatic dicarboxylic acids with distinct rigidities were employed to elucidate their influence on molecular self-assembly, hydrogelation, and functional performance. Hydrogel formation was triggered using a pH-responsive approach, and critical aggregation and gelation concentrations were determined. Morphological analysis by transmission electron microscopy revealed dense fibrillar networks with nanometer-scale fiber diameters, while rheological studies demonstrated viscoelastic behavior, tunable mechanical strength, and, in selected systems, efficient self-healing properties. The incorporation of phenylalanyldehydrophenylalanine significantly enhanced hydrogel formation, highlighting the importance of π–π interactions and hydrophobicity. Biological evaluation using HaCaT keratinocytes confirmed low cytotoxicity across the series. A representative injectable hydrogel exhibited sustained release of the anticancer drug methotrexate, governed predominantly by Fickian diffusion. These results establish clear structure–property–function relationships and demonstrate the potential of symmetrical bolaamphiphilic dehydropeptides as versatile platforms for controlled drug delivery. Full article

Bioadhesive materials capable of operating under aqueous conditions are of considerable interest for biomedical and materials science applications. Peptide-based systems represent an attractive platform for such materials due to their structural tunability, inherent biocompatibility, and ability to form supramolecular networks through noncovalent interactions. In this work, a focused library of tyrosine-containing dehydropeptides was designed and synthesized to investigate how molecular architectures influence self-assembly, hydrogel formation and adhesive properties. The peptides were synthesized using a solution-phase Boc strategy and systematically varied with respect to N-terminal protection and C-terminal functionality. The N-protected dehydropeptides formed supramolecular hydrogels through multiple gelation triggers, including pH reduction and heating–cooling cycles. Rheological characterization confirmed the formation of viscoelastic networks with tunable mechanical properties, with storage moduli reaching tens of kilopascals depending on peptide structure. Scanning electron microscopy revealed dense fibrous nanostructures consistent with supramolecular hydrogel formation. The N,C-deprotected dehydropeptides displayed reduced gelation propensity but formed cohesive films with measurable adhesive performance toward hydrophilic substrates. Lap-shear tests demonstrated high shear strengths for the hydrophilic films, highlighting their structural robustness under stress. Overall, this study provides insights into the structure–property relationships governing tyrosine-containing dehydropeptide assemblies and demonstrates their potential as minimalistic building blocks for supramolecular adhesive materials. Full article

Limited mechanical robustness and prompt proteolytic degradation preclude wider biomedical application of supramolecular peptide hydrogels. Low-molecular-weight dehydropeptides represent a promising class of hydrogelators, owing to their enhanced proteolytic stability, high self-assembly propensity, biocompatibility, and tunable rheological and drug-release properties. Herein, we prepared a small library of N-succinylated dehydrotripeptides (Suc-L-Xaa-L-Phe-Z-ΔPhe-OMe/-OH; Xaa = Phe or Val), together with the canonical analogs (Suc-L-Phe-L-Phe-L-Phe-OMe/-OH), to assess whether in addition to proteolytic resistance, dehydropeptides offer clear advantages over canonical peptides in terms of self-assembly, gelation efficacy, mechanical performance, and cargo release. Peptide self-assembly, hydrogel formation, and supramolecular organization were investigated by fluorescence and circular dichroism (CD) spectroscopy, molecular dynamic (MD) simulations, Thioflavin T hydrogel staining, ATR-FTIR spectroscopy, transmission electron microscopy (TEM), and rheological measurements. Drug-release performance was evaluated using methyl orange as a model cargo. Overall, the dehydropeptide-based hydrogels displayed enhanced gelation efficacy, improved mechanical properties, and sustained release profiles compared to canonical analogs. Spectroscopic analysis (CD and ATR-FTIR) and molecular dynamic simulations indicated that the dehydropeptides preferentially self-assemble into more ordered supramolecular fibrils, with extended β-sheet-like packing, whereas the canonical peptides predominantly populate more disordered backbone environments. Proteolysis assays with α-chymotrypsin revealed that both canonical and dehydropeptide methyl esters underwent chymotrypsin-catalyzed ester hydrolysis. Importantly, only the canonical dicarboxylic acid underwent further proteolytic degradation. The dehydropeptide dicarboxylic acids revealed fully resistant to proteolysis over extended time periods. These results demonstrate that the incorporation of dehydroamino acid into peptides enables control over supramolecular packing, nanofibrillar network architecture, rheology, and cargo release. This report raises the profile of relatively underexplored dehydropeptide-based soft materials as promising high-performance biomaterials for technological and biomedical applications. Full article

Intracerebral hemorrhage (ICH) remains a devastating condition with no available therapies that can effectively mitigate secondary injury and promote neurological repair. This research presents a novel combinatorial regenerative strategy, concurrently delivering adipose-derived stromal vascular fraction (SVF) within an adhesive self-assembling peptide (HGF-RADA16-IKVAV) nanohydrogel (HGF). In a clinically relevant rat model of ICH with hematoma evacuation, the combined therapy of HGF and SVF demonstrated synergistic and enhanced efficacy. In the short term, the combined therapy demonstrated hemostatic benefits, and significantly reduced hematoma volume, brain edema, neuronal apoptosis and neuroinflammation indicated by pro-inflammatory markers (NLRP3, caspase-1, Iba-1, CD68, GFAP) while increasing the levels of anti-inflammatory (CD206) and angiogenic (CD31) markers. Longitudinal behavioral assessments conducted over six weeks demonstrated persistent and significant improvements in motor coordination, forelimb strength, and gait parameters within the HGF + SVF group, surpassing all monotherapies. Ultrastructural analysis also showed that myelinated axons were better preserved at the injury border, with thicker myelin sheaths. These findings demonstrate that the co-administration of SVF with an adhesive and hemostatic hydrogel collaboratively diminishes secondary injury, modulates neuroinflammation, and promotes functional and structural brain recovery following ICH, indicating a promising and translatable strategy. Full article

Background: Postoperative bleeding is a frequent complication in otolaryngology and head and neck surgery, often leading to readmissions and increased healthcare costs. Objectives: This systematic review evaluates the clinical efficacy, safety, and impact of RADA16, a synthetic self-assembling peptide hydrogel, as a topical haemostatic adjunct in this surgical field. Methods: In adherence with PRISMA 2020 guidelines, a systematic search of PubMed, Scopus, and Web of Science was conducted through December 2025. Eligible studies included adult patients undergoing otolaryngological or head and neck surgical procedures where RADA16 (CAS 289042-25-7, PuraBond^®/PuraStat^®/PuraGel^®, ^®, 3-D Matrix SAS; Caluire et Cuire, Lyon, France) was applied intraoperatively. Exclusion criteria included non-English publications, reviews, and studies without clinical outcome data. Risk of bias was assessed using the Cochrane Risk of Bias tool for RCTs and the Newcastle-Ottawa Scale for observational studies. A narrative synthesis was performed due to heterogeneity in outcome reporting. Results: Eight studies involving 1761 patients were included. In oropharyngeal surgery, RADA16 significantly reduced postoperative haemorrhage (6.3% vs. 16.7%, p = 0.016) and was associated with faster resumption of normal diet and lower pain scores (p = 0.016). In nasal surgery, it significantly lowered epistaxis rates (0.4% vs. 2.2%, adjusted OR 0.027, p = 0.026) and reduced the need for nasal packing. In cervical endocrine surgery, the rate of hematoma requiring revision was low (0.84%), with no delayed bleeding beyond 24 h. Surgeons consistently reported high satisfaction and ease of application. No serious device-related adverse events were reported. Discussion: Current evidence suggests RADA16 is a safe and effective haemostatic adjunct that can improve postoperative recovery and reduce readmission rates in specific surgical contexts. Limitations include heterogeneity in study designs, small sample sizes in some domains, and a lack of long-term follow-up. Further large-scale randomized controlled trials are needed to quantify its economic impact and formalize its role in surgical pathways. Funding: This study was funded by 3-D Matrix Medical Technology for article processing charges. The funder had no role in study design, data collection, analysis, interpretation, or writing. Registration: This review was not registered in a systematic review registry. Full article

Herpes simplex virus type 1 (HSV-1) is a neurotropic alphaherpesvirus that interacts dynamically with host cells within structured tissue environments. Conventional two-dimensional (2D) cultures do not fully recapitulate these spatial and microenvironmental features. In this study, we established a three-dimensional (3D) culture system using the self-assembling peptide RADA16-I to generate an extracellular matrix–mimetic hydrogel scaffold. This platform supported the formation of stable Vero cell spheroids that remained viable for more than 30 days. Following HSV-1 infection, viral spread initiated at the spheroid periphery and progressively extended toward the core. Sustained viral replication was detected for up to 22 days, indicating long-term maintenance of infection within the 3D structure. Ultrastructural examination identified viral particles and vesicular compartments consistent with autophagy-related organelles. Comparative analysis of autophagy-associated markers revealed distinct temporal patterns between 2D monolayer cultures and 3D spheroids. In the 3D system, LC3B-II levels progressively increased, accompanied by a reduction in p62, suggesting altered regulation of autophagic flux relative to conventional 2D conditions. These findings demonstrate that the RADA16-I-based 3D culture model supports prolonged HSV-1 infection and reproduces key spatial features of viral dissemination. The differential autophagic responses observed between 2D and 3D systems highlight the influence of cellular architecture on host–virus interactions and support the application of 3D culture platforms for mechanistic studies of HSV-1 pathogenesis. Full article

Chronic wounds and implanted medical devices remain highly vulnerable to biofilm-associated infections, which resist conventional antibiotics and immune clearance. Synthetic antimicrobial peptides (AMPs) have emerged as promising alternatives, offering tunable sequences, short lengths for cost-effective synthesis, and functional modifications that enhance stability and antibiofilm potency. Hydrogels provide an optimal delivery matrix by enabling localized AMP release, maintaining a moist wound environment, and supporting stimuli-responsive or sustained therapeutic action. This review highlights recent advances in peptide engineering strategies—including rational sequence design, chemical modifications, and self-assembling nanostructures—alongside hydrogel integration approaches ranging from physical entrapment to covalent tethering and infection-triggered release systems. Mechanistic insights into antibiofilm activity are discussed, supported by in vitro, ex vivo, and in vivo evaluation models. Beyond antimicrobial efficacy, multifunctional AMP–hydrogel systems can deliver complementary benefits such as hemostasis, anti-inflammation, or enzymatic biofilm dispersal, further accelerating tissue repair. Despite significant progress, translational challenges remain, including peptide stability, manufacturing costs, regulatory hurdles, and host safety. Future directions point toward AI-driven peptide design, programmable hydrogels, and point-of-care integration to realize safe, effective, and multifunctional AMP–hydrogel therapies for chronic wound management and biofilm eradication. Full article

The overuse of antibiotics has accelerated the evolution and mutation of drug-resistant bacteria, creating an urgent need for novel antimicrobial drugs and feed additives. Antimicrobial peptides, with their unique membrane-disrupting mechanism that resists the development of resistance, hold promise as antibiotic alternatives. To overcome the limitations of natural antimicrobial peptides—such as poor stability, susceptibility to protease degradation, and short in vivo half-lives—self-assembling peptide technology has emerged. This approach employs non-covalent interactions to orderly assemble monomeric peptides into stable, structured nanomaterials like nanofibers, nanotubes, and hydrogels. This paper outlines the molecular design principles and smart response mechanisms of antimicrobial peptide nanoassemblies, elucidates their core advantages over monomeric peptides, summarizes their application scenarios in anti-infection fields, and discusses limitations and future directions across various domains. It provides insights for future antimicrobial peptide design. Full article

Peptide-based biomaterials have emerged as versatile tools for pharmaceutical drug delivery due to their biocompatibility and tunable sequences, yet a comprehensive overview of their categories, mechanisms, and optimization strategies remains lacking to guide clinical translation. This review systematically collates advances in peptide-based biomaterials, covering peptide excipients (cell penetrating peptides, tight junction modulating peptides, and peptide surfactants/stabilizers), self-assembling peptides (peptide-based nanospheres, cyclic peptide nanotubes, nanovesicles and micelles, peptide-based hydrogels and depots), and peptide linkers (for antibody drug-conjugates, peptide drug-conjugates, and prodrugs). We also dissect sequence-based optimization strategies, including rational design and biophysical optimization (cyclization, stapling, D-amino acid incorporation), functional motif integration, and combinatorial discovery with AI assistance, with examples spanning marketed drugs and research-stage candidates. The review reveals that cell-penetrating peptides enable efficient intracellular payload delivery via direct penetration or endocytosis; self-assembling peptides form diverse nanostructures for controlled release; and peptide linkers achieve site-specific drug release by responding to tumor-associated enzymes or pH cues, while sequence optimization enhances stability and targeting. Peptide-based biomaterials offer precise, biocompatible and tunable solutions for drug delivery, future advancements relying on AI-driven design and multi-functional modification will accelerate their transition from basic research to clinical application. Full article

Ultra-short peptides (USPs; ≤7–8 amino acids) emerge as minimal self-assembling building blocks for hydrogel-based biomaterials. Their intrinsic biocompatibility, straightforward synthesis, and ease of tunability make them particularly attractive candidates for potential use in bioprinting. This review provides an overview of the properties of USPs along with their applications in three-dimensional (3D) bioprinting. We first discuss how peptide sequence, terminal and side-chain modifications, and environmental triggers govern USPs’ self-assembly into nanofibers and 3D networks and how these supramolecular features translate into key rheological properties such as shear-thinning, rapid gelation, and mechanical tunability. We then survey reported applications in tissue engineering, wound healing, and organotypic models, as well as emerging ultra-short peptide-based systems for drug delivery, biosensing, and imaging, highlighting examples where printed constructs support cell viability, differentiation, and matrix deposition. Attention is given to hybrid and multi-material formulations in which USPs provide bioactivity while complementary components contribute structural robustness or additional functionality. Finally, this review outlines the main challenges that currently limit widespread adoption, including achieving high print fidelity with cytocompatible crosslinking, controlling batch-to-batch variability, and addressing the scalability, cost, and sustainability of peptide manufacturing. We conclude by discussing future opportunities such as AI-assisted peptide design, adaptive and multi-material bioprinting workflows, and greener synthetic routes, which together may accelerate the translation of ultra-short peptide-based bioinks from proof-of-concept studies to clinically and industrially relevant platforms. Full article