Immunomodulation in Bone Tissue Engineering: Recent Advancements in Scaffold Design and Biological Modifications for Enhanced Regeneration

ACS Biomaterials Science & Engineering, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

Bone defects, whether caused by trauma, cancer, infectious diseases, or surgery, can significantly impair people's quality of life. Although autografts are the gold standard for treating bone they often fall short in adequately forming tissue. The field tissue engineering has made strides using scaffolds with various biomaterials, stem cells, and growth factors to enhance healing. However, some biological structures do not yield satisfactory therapeutic outcomes new formation. Recent studies have shed light on crucial role immunomodulation, specifically interaction between implanted scaffold host immune systems, regeneration. Immune particularly macrophages, pivotal inflammatory response, angiogenesis, osteogenesis. This review delves into system's mechanism toward foreign bodies recent advancements scaffolds' physical properties that foster regeneration modulating macrophage polarization an anti-inflammatory phenotype enhancing osteoimmune microenvironment.

Language: Английский

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Nanofibrous Microspheres: A Biomimetic Platform for Bone Tissue Regeneration

ACS Applied Bio Materials, Journal Year: 2024, Volume and Issue: 7(7), P. 4270 - 4292

Published: July 1, 2024

Bone, a fundamental constituent of the human body, is vital scaffold for support, protection, and locomotion, underscoring its pivotal role in maintaining skeletal integrity overall functionality. However, factors such as trauma, disease, or aging can compromise bone structure, necessitating effective strategies regeneration. Traditional approaches often lack biomimetic environments conducive to efficient tissue repair. Nanofibrous microspheres (NFMS) present promising platform regeneration by mimicking native extracellular matrix architecture. Through optimized fabrication techniques incorporation active biomolecular components, NFMS precisely replicate nanostructure biochemical cues essential osteogenesis promotion. Furthermore, exhibit versatile properties, including tunable morphology, mechanical strength, controlled release kinetics, augmenting their suitability tailored engineering applications. enhance cell recruitment, attachment, proliferation, while promoting osteogenic differentiation mineralization, thereby accelerating healing. This review highlights engineering, elucidating design principles key attributes. By examining recent preclinical applications, we assess current clinical status discuss critical considerations potential translation. offers crucial insights researchers at intersection biomaterials highlighting developments this expanding field.

Language: Английский

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Enhanced Bone Targeting of Poly(l-glutamic acid)s through Cationic or Aromatic Substitution

Biomacromolecules, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 20, 2025

Poly(l-glutamic acid)s (PLGs) are promising bone-targeting ligands due to their high molecular weight and facile preparation. Nevertheless, the efficiency of PLGs is still relatively low, validating necessity further enhance targeting through structural optimization. Herein, we report use a heteropolypeptide strategy improve bone incorporation another side-chain functionality for enhanced affinity with tissues. Specifically, introduction cationic amino or aromatic phenolic residues resulted in ∼2.3-fold ∼1.6-fold increase vivo targeting, respectively. Cationic modification not only improved minerals but also exhibited prolonged retention tissues more than 60 days. This work highlights library screen optimize performance polypeptide materials, offering polymeric materials design bone-related nanomedicine.

Language: Английский

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Mechanistic Insights of Amino Acid Binding to Hydroxyapatite: Molecular Dynamics Charts Future Directions in Biomaterial Design

Langmuir, Journal Year: 2024, Volume and Issue: 40(42), P. 22136 - 22144

Published: Oct. 10, 2024

Extensive efforts have been made to improve the understanding of hard tissue regeneration, essential for advancing medical applications like bone graft materials. However, mechanisms biomineralization, particularly regulation hydroxyapatite growth by proteins/peptides, remain debated. Small biomolecules such as amino acids are ideal studying these due their simplicity and relevance protein/peptide building blocks. This study investigates binding affinity four including glycine (Gly), proline (Pro), lysine (Lys), aspartic acid (Asp) (HAP) (100) surface through molecular dynamics simulations. Our findings reveal that exhibits most energetically favorable affinity, attributed its additional carboxylate group (−COO–), which facilitates stronger interactions with Ca2+ ions on HAP compared other single groups. highlights critical role specific functional groups in modulating strength, emphasizing presence multiple sites enhances stability. Interestingly, also uncovers significance water-mediated interactions, compact water layer above acts a barrier, complicating direct underscoring need consider solvation effects Glycine, small size, demonstrates unique ability penetrate this tightly bound monolayer, suggesting size influences dynamics. These simulations offer detailed insights into atomic-level providing deeper pertinent designing peptides or proteins enhanced biomaterials, mimicking natural bone-binding processes.

Language: Английский

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Correction to “Nanofibrous Microspheres: A Biomimetic Platform for Bone Tissue Regeneration”

ACS Applied Bio Materials, Journal Year: 2024, Volume and Issue: 7(9), P. 6325 - 6331

Published: Aug. 20, 2024

Language: Английский

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Farnesyl pyrophosphate synthase inhibitors with antiosteoporosis efficacy in ovariectomized rats: A mixed binding approach beyond bisphosphonates

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 276, P. 116679 - 116679

Published: July 14, 2024

Language: Английский

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Selection of Bone-Targeting Peptides for Therapeutic Intervention: An In Vivo Evaluation and Comparison Study

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Abstract Hydroxyapatite (HA)-binding peptides are emerging as promising candidates for bone-targeted therapies due to their strong affinity mineralized tissues and biocompatibility. However, most studies date have focused on in vitro characterization, providing limited insight into vivo performance. This study bridges that gap by evaluating the behavior of HA-binding D8, E8, YD8, YE8 using fluorescence imaging assess biodistribution healthy pathological bone environments. In animal models, D8 demonstrated strongest binding across tissues, including skull, femur, tibia, while YD8 showed moderate binding. contrast, E8 exhibited localization influenced peptide dosage kinetics. Pathological defective tibia osteogenesis imperfecta (OIM) mice, revealed preferential accumulation structurally compromised regions, underscoring potential targeting diseased microenvironments. Fluorescence imaging, enhanced spectral unmixing algorithms, proved effective assessing distribution. These findings highlight utility emphasize importance advancing therapeutic diagnostic applications. work provides a foundation optimizing designs improve specificity efficacy repair regeneration.

Language: Английский

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Selection of Bone-Targeting Peptides for Therapeutic Intervention: An In Vivo Evaluation and Comparison Study

Published: Dec. 24, 2024

Hydroxyapatite (HA)-binding peptides are emerging as promising candidates for bone-targeted therapies due to their strong affinity mineralized tissues and biocompatibility. However, most studies date have focused on _in vitro_ characterization, providing limited insight into vivo_ performance. This study bridges that gap by evaluating the behavior of HA-binding D8, E8, YD8, YE8 using fluorescence imaging assess biodistribution in healthy pathological bone environments. In animal models, D8 demonstrated strongest binding across tissues, including skull, femur, tibia, while YD8 showed moderate binding. contrast, E8 exhibited localization influenced peptide dosage kinetics. Pathological defective tibia osteogenesis imperfecta (OIM) mice, revealed preferential accumulation structurally compromised regions, underscoring potential targeting diseased microenvironments. Fluorescence imaging, enhanced spectral unmixing algorithms, proved effective assessing distribution. These findings highlight utility emphasize importance advancing therapeutic diagnostic applications. work provides a foundation optimizing designs improve specificity efficacy repair regeneration.

Language: Английский

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Construction of Nanohydroxyapatite/Poly(sodium lipoate)-Based Bioactive Hydrogels for Cranial Bone Regeneration

Biomacromolecules, Journal Year: 2024, Volume and Issue: 26(1), P. 705 - 714

Published: Dec. 28, 2024

Persistent oxidative stress following bone defects significantly impedes the repair of tissue. Designing an antioxidative hydrogel with a suitable mechanical strength can help alter local microenvironment and promote defect healing. In this work, α-lipoic acid (LA), natural antioxidant small molecule, was chemically cross-linked lipoic acid-functionalized poly(ethylene glycol) (PEGx, x = 6k or 10k) in sodium bicarbonate solution, to prepare LA-PEGx hydrogels (LPx, 10k). Furthermore, nanohydroxyapatite (nHA)-LA-PEGx (HLPx, 6k) were constructed through incorporating nHA. The exhibited moderate strength, facile injectability, self-healability, adhesion, biodegradability, biocompatibility, promising antioxidation efficiency. We verify advantage HLP6k-3 rat cranial model. Through regulation reactive oxygen species (ROS), osteoconduction, biomineralization capabilities, our system new formation. Overall, bioactive multiple functions hold significant promise for repairing defects.

Language: Английский

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