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Journal of Functional Biomaterials · 2023 ·Vol. 14 ·期 7 ·360 · IF 4.8

Properties of Dual-Crosslinked Collagen-Based Membranes as Corneal Repair Material

Lulu Wang,Yuehai Peng,Wenfang Liu,Li Ren

Corneal disease has become the second leading cause of blindness in the world. Corneal transplantation is currently considered to be one of the common treatments for vision loss. This paper presents a novel approach utilizing dual-crosslinked membranes composed of polyrotaxane multiple aldehydes (PRAs), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), and N-hydroxysuccinimide (NHS) in the development process. Collagen was crosslinked, respectively, by EDC/NHS and PRAs to form stable amide bonds and imine groups. Through the formation of a double interpenetrating network, dual-crosslinked (Col-EDC-PRA) membranes exhibited enhanced resistance to collagenase degradation and superior mechanical properties compared to membranes crosslinked with a single crosslinker. Furthermore, Col-EDC-PRA membranes display favorable light transmittance and water content characteristics. Cell experiments showed that Col-EDC-PRA membranes were noncytotoxic and were not significantly different from other membranes. In a rabbit keratoplasty model, corneal stromal repair occurred at 5 months, evidenced by the presence of stromal cells and neo-stroma, as depicted in hematoxylin–eosin-stained histologic sections and optical coherence tomography images of the anterior segment. Moreover, there was no inflammation and corneal neovascularization, as well as no corneal rejection reaction in the surgical area. Overall, the results demonstrated that the dual-crosslinked membranes served effectively for corneal tissue regeneration after corneal defect.Keywords:collagen membrane;corneal repair;corneal regeneration

研究领域: 生物医学工程 · 眼科研究
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Materials Science & Engineering C-Materials for Biological Applications · 2019 · IF 4.959

Fabrication of collagen membranes with different intrafibrillar mineralization degree as a potential use for GBR

Jing Wang,Yinan Qu,Chaoqun Chen,Jian Sun,Haihua Pan,Changyu Shao,Ruikang Tang,Xinhua Gu

The process of biomineralization in dentin and bone tissue repair has been extensively studied. In vitro, biomineralization can be stimulated via a polymer-induced liquid precursor (PILP) process. Guided bone regeneration using a barrier membrane and bone substitute materials is widely used in implantology in cases where there is insufficient bone volume. Herein, we applied a homologous PILP processes to fabricate collagen films with a varying degree of mineralization and tested their performance. The results showed that the prepared biomineralized membranes are biocompatible, have a high stress strength and can promote MC3T3-e1 cell proliferation . This indicated that the membranes can be potentially applied in guided bone regeneration, with membranes containing a higher degree of mineralization achieving the best results.

研究领域: 医学 · 材料科学 · 组织工程
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Journal of Materials Chemistry B · 2024 ·Vol. 12 ·期 29 ·7171-7190 · IF 6.1

A multifunctional collagen-base bilayer membrane integrated with a bimetallic/polydopamine network for enhanced guided bone regeneration

Dou Huang,Die Yang,Kaide Li,Jiran Wang,Xiaohui Zheng,Jie Long,Lei Liu

The guided bone regeneration (GBR) technique is an effective treatment for small and medium-sized bone defects in the oral and maxillofacial region. However, currently available collagen membranes have limited functionality and are inadequate for clinical requirements. To address this challenge, this study pioneeringly developed a multifunctional bilayer membrane. Specifically, a bimetallic/polydopamine network (BPN), consisting of silver, magnesium, and dopamine, was successfully synthesized for the first time and integrated with collagen and hydroxyapatite. The resulting material was characterized, and its physicochemical properties, along with its barrier, osteogenic, angiogenic, antibacterial, hemostatic, and biosafety effects, were evaluated through both in vitro and in vivo studies. The results indicated that the BPN, composed of magnesium ions, silver nanoparticles (Ag NPs), and polydopamine (PDA), exhibited excellent thermal stability and slow release of silver and magnesium elements. The BPN/Col-HA membrane featured a bilayer structure with uniform distribution of silver and magnesium. It also demonstrated good hydrophilicity, suitable degradation and mechanical properties, as well as sustained release of silver and magnesium. In vitro experiments showed that the BPN/Col-HA membrane possessed desirable barrier, osteogenic, angiogenic, antibacterial, hemostatic, and biocompatible properties. In vivo results further confirmed its biosafety, hemostatic efficacy, and ability to effectively promote bone defect repair and angiogenesis. Thus, the BPN/Col-HA membrane emerges as a multifunctional GBR membrane with potential for clinical translation.

CAS / MDL: 64-19-7 7558-80-7
研究领域: 生物医学工程 · 口腔医学 · 材料科学
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Biomedical Materials · 2024 ·Vol. 19 ·期 5 ·055009 · IF 3.9

Performance of a multiphase bioactive socket plug with a barrier function for alveolar ridge preservation

Chao Yao,Prisana Pripatnanont,Junbiao Zhang,Srisurang Suttapreyasri

The natural healing process of extraction socket and traditional socket plug material could not prevent buccal bone wall resorption and down growth of epithelium from the socket orifice. A multiphase bioactive socket plug (BP) is designed to overcome the natural healing process by maintaining the three-dimensional (3D) volume of extraction sockets, particularly in sockets with wall defects, and later provide sufficient alveolar bone volume for implant placement. The study aimed to fabricate and evaluate the physical, chemical, and biological performance of BP in vitro. The BP was fabricated through freeze-drying and layer-by-layer assembly, comprised of a base serving as a scaffold, a central portion for promoting bone regeneration, an upper buccal portion for maintaining alveolar socket dimension with a covering collagen membrane (Memb) on the top and upper buccal surface to prevent soft tissue infiltration. The BP as the experimental group and a pure collagen plug (CP) as the control group were investigated and compared. Radiograph, scanning electron microscopy, and energy-dispersive spectroscopy mapping confirmed that the four-part BP was successfully assembled and fabricated. Swelling rate analysis indicated that BP, CP, and Memb reached swelling equilibrium within 1 hour. BP exhibited a high remaining weight percentage in collagenase solution (68.81 ± 2.21% on day 90) and sustained calcium ion release, reaching the maximum 0.13 ± 0.04 mmol l−1 on day 14. In biological assays, BP exhibited excellent cell proliferation (The OD value increased from 0.02 on day 1 to 0.23 on day 21.). The BP group exhibited higher alkaline phosphatase activity and osteocalcin content than the CP group within 21 days. Memb and BP exhibited outstanding barrier function, as evidenced by Hematoxylin and eosin staining. In summary, the multiphase bioactive socket plug represents a promising scaffold for alveolar ridge preservation application.

研究领域: 口腔医学 · 生物材料学
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ANALYTICA CHIMICA ACTA · 2025 · IF 6

An MA-film platform designed for high-throughput synthesis of calcium phosphates screening amino acid on collagen film

Xiaoyu Li,Xiran Yang,Xinkun Chen,Changxia Liu,Linlin Wu,Dazhuo Qiu,Xueye Chen,Xuetao Shi

Background Calcium phosphate is recognized as the primary inorganic mineral component found in rigid biological tissues; its deposition within living organisms is regulated by organic matrices such as collagen and amino acids. Previous research has mainly relied on trial-and-error methods, which are often time-consuming and resource-intensive. To address this, there now exists a pressing need for more efficient approaches, to systematically explore the contributions of various organic molecules such as amino acids and collagen governing the mechanisms of calcium phosphate synthesization and mineralization. Results We designed an MA-Film platform with on-film high-throughput synthesis and screening functions. By establishing a concentration gradient of the pertinent reagent inside the platform, a series of desired products could be rapidly synthesized on the selected film. We utilized the platform to perform the biomimetic synthesis of calcium phosphates on type I collagen films. The collagen film was deposited onto the platform's silicon chip through spin-coating while concentration gradients of aspartic acid (Asp), glycine (Gly), and lysine (Lys) were generated to observe the influence of amino acids on the formation of calcium phosphate. The results indicated that the presence of carboxyl and carbonyl groups within collagen molecules would create potential nucleation sites for crystal formation, and the morphology and crystal structure of the calcium phosphates were strongly influenced by the properties and concentrations of amino acids. Significance The designed MA-Film platform provides a highly efficient, rapid, and user-friendly approach for biomimetic mineralization research by conducting 36 synthetic experiments in parallel on specific thin films through the construction of target reagent concentration gradients. And as a general-purpose tool, the platform is expected to facilitate high-throughput screening and synthesis studies across diverse materials.

研究领域: 材料科学 · 生物化学 · 生物矿化 · 纳米技术 · 高通量筛选
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2023 · IF 8.2

Collagen membrane loaded with doxycycline through hydroxypropyl chitosan microspheres for the early reconstruction of alkali-burned cornea

Jia Liu,Yingni Xu,Yongrui Huang,Xiaomin Sun,Yuehai Peng,Wenjing Song,Jin Yuan,Li Ren

Corneal alkali burn is one of the most devastating ophthalmic emergencies correlated with remarkable morbidity resulting in severe visual impairment. Appropriate intervention in the acute phase determines the eventual outcome for later corneal restoration treatment. Since the epithelium plays an essential role in inhibiting inflammation and promoting tissue repair, sustained anti-matrix metalloproteinases (MMPs) and pro-epithelialization are the prior remedies during the first week. In this study, a drug-loaded collagen membrane (Dox-HCM/Col) that could be sutured to overlay the burned cornea was developed to accelerate the early reconstruction. Doxycycline (Dox), a specific inhibitor of MMPs, was encapsulated in collagen membrane (Col) through hydroxypropyl chitosan microspheres (HCM) to develop Dox-HCM/Col, affording a preferable pro-epithelialization microenvironment and an in-situ controlled release. Results showed that loading HCM into Col prolonged the release time to 7 days, and Dox-HCM/Col could significantly suppress the expression of MMP-9 and -13 in vitro and in vivo . Furthermore, the membrane accelerated the corneal complete re-epithelialization and promoted early reconstruction within the first week. Overall, Dox-HCM/Col was a promising biomaterial membrane for treating alkali-burned cornea in the early stage, and our attempt may provide a clinically feasible method for the ocular surface reconstruction.

研究领域: 眼科 · 生物材料 · 组织工程 · 药学
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ACS Applied Bio Materials · 2019 · IF 0

Mechanical and Optical Properties of Reinforced Collagen Membranes for Corneal Regeneration through Polyrotaxane Cross-Linking

Xiaoyue Lei,Yong-Guang Jia,Wenjing Song,Dawei Qi,Jiahong Jin,Jia Liu,Li Ren

Corneal transplantation is the widely accepted treatment to restore sight for corneal blindness. To date, because of the global donor cornea shortage, there is a need for alternatives to human donor corneas. Biocompatible collagen is an excellent candidate material for corneal repair in the view of biomimetics. Herein a class of polyrotaxane multiple aldehyde (PRA) cross-linkers based on the host–guest supramolecules of α-cyclodextrins and poly(ethylene glycol) is prepared to cross-link with collagen to fabricate materials for corneal repair. Aldehyde groups from rotaxanes and α-cyclodextrin units can synergistically improve the mechanical and optical properties of PRA cross-linked collagen membranes (Col-PRAs). Compared with counterparts cross-linked by traditional a cross-linker of 1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide and N-hydroxy-succinimide, Col-PRAs have better mechanical properties, especially suture resistance as well as optical properties. In vivo lamellar keratoplasty results indicate that Col-PRAs not only can bear tight suturing on a rabbit cornea but also are prone to the remodeling of the epithelium and stroma of the cornea due to the outstanding cell adhesion and proliferation. These novel Col-PRAs exhibit great potential for use in the corneal regeneration.

研究领域: 材料科学 · 生物医学工程 · 眼科学
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FOOD CHEMISTRY · 2022 · IF 9.231

Enhanced physicochemical and functional properties of collagen films cross-linked with laccase oxidized phenolic acids for active edible food packaging

Pingping Tang,Tingting Zheng,Changkai Yang,Guoying Li

Five different phenolic acids were oxidized by laccase. The UV–vis and FTIR results of oxidized phenolic acids indicated the formation of quinones and the amount of quinones enhanced with the increased phenolic   hydroxyl   number of phenolic acids. Then the quinones were used to modify collagen film. The FTIR and X-ray photoelectron spectra indicated that covalent cross-linking had formed between the quinones and the –NH 2 of collagen molecules. Collagen films after being cross-linked with the quinones exhibited better physicochemical properties including water vapor permeability, resistance to enzyme degradation, mechanical property and thermostability. And these properties were significantly improved with the increased phenolic hydroxyl number of phenolic acids. Besides, the introduction of the phenolic acids endowed collagen film good antioxidant and antibacterial capacities. These results indicated that collagen film cross-linked by laccase oxidized phenolic acids showed potential for application as active edible food packaging.

研究领域: 材料科学 · 食品科学 · 化学
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ACS Biomaterials Science & Engineering · 2025 · IF 5.5

Multifunctional Three-Layer Collagen-Based Membrane for Periodontal Guided Tissue Regeneration

Sara Takallu,Zeinab Karimi,Hooman Khorshidi,Abdollah Bazargani,Amin Bigham-Sadegh,Simin Torabi Nezhad,Esmaeil Mirzaei

Guided tissue regeneration (GTR) and guided bone regeneration (GBR) are pivotal surgical techniques for addressing periodontal defects arising from periodontitis. These methods utilize barrier membranes to isolate soft tissue from bone defects, preventing premature fibroblast infiltration and promoting osteoblast colonization. However, infections caused by periodontitis-associated pathogens significantly elevate the risk of membrane failure, underscoring the need for advanced membrane designs. This study introduces a multifunctional membrane, known as guided tissue/bone regeneration membrane (GTBRM), engineered to optimize composition, structure, and bioactivity. The GTBRM comprises two porous collagen layers for soft and hard tissue regeneration and 2% silver nanoparticles (AgNPs) and β-tricalcium phosphate nanoparticles (β-TCP NPs) for antibacterial and osteogenic properties, respectively, and a dense poly(vinyl alcohol) (PVA)/cellulose nanocrystal (CNC) core for mechanical strength and cell occlusion. Physicochemical properties of the membrane were characterized using scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDAX), X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, tensile strength testing, and biodegradation assessments. In vitro studies with MG-63 cells, human gingival fibroblasts (HGF), and bone marrow mesenchymal stem cells (BMSCs) demonstrated biocompatibility, cell adhesion, proliferation, and osteogenic differentiation. The incorporation of AgNPs conferred significant antibacterial efficacy against Enterococcus faecalis (E. faecalis) and Fusobacterium nucleatum (F. nucleatum), and β-TCP NPs enhanced osteoblast activity. In vivo studies in rat radial bone and oral defect models revealed that GTBRM markedly improved osteogenesis and buccal soft tissue regeneration. These preclinical findings suggest that the GTBRM exhibits potential for periodontal regeneration by providing biocompatibility, space maintenance, antibacterial properties, and osteoconductivity. However, further studies are needed to validate its clinical efficacy and translational potential.

CAS / MDL: 123-03-5
研究领域: 生物材料 · 组织工程 · 再生医学 · 纳米技术 · 生物医学工程 · 牙科 · 微生物学 · 材料科学
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RSC Advances · 2018 ·Vol. 8 ·期 32 ·18153-18162 · IF 2.936

An antibacterial collagen membrane crosslinked by the inclusion complex of β-cyclodextrin dialdehyde and ofloxacin for bacterial keratitis

Yawei Chen,Wenjing Song,Xuan Zhao,Qianqian Han,Li Ren

Infectious keratitis is one of the leading causes of blindness in the world, especially in developing countries. Corneal transplant surgery is a feasible treatment for bacterial keratitis when drug therapy cannot be effective. However, the amount of corneal donors is far from requirements of clinical treatment and thus, the prognosis of bacterial keratitis is not satisfactory. In this study, we developed a novel antibacterial corneal repair material (β-CD-DA/OFLX-Col) for bacterial keratitis. The inclusion complex of β-cyclodextrin dialdehyde (β-CD-DA) with ofloxacin formed by host–guest interaction was used as both a drug vector and a crosslinker for further reaction with the amino groups on lysine of collagen chains. Physical properties, cytocompatibility, and antibacterial property of β-CD-DA/OFLX-Col film were characterized. The results indicated that the film was mainly transparent and possessed superior mechanical properties. Moreover, human corneal epithelial cells could adhere to the film and proliferate normally, indicating that the β-CD-DA/OFLX-Col film was non-cytotoxic and had good biocompatibility. Most importantly, the β-CD-DA/OFLX-Col film exhibited prominent antibacterial effects against E. coli and S. aureus in vitro, which could minimize the risks of infection. The prepared β-CD-DA/OFLX-Col film could greatly increase bioavailability of drugs and reduce toxic side effects, thus displaying great potential in bacterial keratitis treatment.

研究领域: 眼科学 · 材料科学 · 药学
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ADVANCED FUNCTIONAL MATERIALS · 2021 ·Vol. 31 ·期 43 ·2105348 · IF 18.808

Biomimetic Lamellar Chitosan Scaffold for Soft Gingival Tissue Regeneration

Yanhuizhi Feng,Huai-Ling Gao,Di Wu,Yu-Teng Weng,Ze-Yu Wang,Shu-Hong Yu,Zuolin Wang

Mucogingival surgery has become a common procedure for soft gingival tissue reparation in dental clinical practice, which mainly relies on autograft or commercial collagen membranes (CM). However, the autograft faces grand challenges in source availability and long-term post-surgery pain management, and the CM is restricted by its poor mechanical properties in an aqueous environment. Here, it is reported that a bio-inspired lamellar chitosan scaffold (LCS) with long range ordered porous structure, manufactured through a bidirectional freezing method, can serve as a promising gingival tissue engineering material. The LCS not only exhibits excellent mechanical properties in the hydrated state but also accelerates vessel formation and soft tissue regeneration in vivo. Most interestingly, the LCS is found to be capable of inducing macrophage differentiation to M2 macrophages, which is thought to play an important role in tissue regeneration. These advantages combined with its easy and low-cost preparation process make the LCS a promising candidate for dental clinical applications.

研究领域: 口腔临床实践 · 组织工程 · 生物医用材料
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Biomimetic tri-layered artificial skin comprising silica gel-collagen membrane-collagen porous scaffold for enhanced full-thickness wound healing

Jing Tian,Caihong Fu,Wenhua Li,Na Li,Linyan Yao,Jianxi Xiao

Full-thickness wounds are severe cutaneous damages with destroyed self-healing function, which need efficient clinical interventions. Inspired by the hierarchical structure of natural skin, we have for the first time developed a biomimetic tri-layered artificial skin (TLAS) comprising silica gel-collagen membrane-collagen porous scaffold for enhanced full-thickness wound healing. The TLAS with the thickness of 3–7 mm displays a hierarchical nanostructure consisting of the top homogeneous silica gel film, the middle compact collagen membrane, and the bottom porous collagen scaffold, exquisitely mimicking the epidermis, basement membrane and dermis of natural skin, respectively. The 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide/N-Hydroxysuccinimide-dehydrothermal (EDC/NHS-DHT) dual-crosslinked collagen composite bilayer, with a crosslinking degree of 79.5 %, displays remarkable biocompatibility, bioactivity, and biosafety with no risk of hemolysis and pyrogen reactions. Notably, the extra collagen membrane layer provides a robust barrier to block the penetration of silica gel into the collagen porous scaffold, leading to the TLAS with enhanced biocompatibility and bioactivity. The full-thickness wound rat model studies have indicated the TLAS significantly facilitates the regeneration of full-thickness defects by accelerating re-epithelization, collagen deposition and migration of skin appendages. The highly biocompatible and bioactive tri-layered artificial skin provides an improved treatment for full-thickness wounds, which has great potential in tissue engineering.

CAS / MDL: 25952-53-8 6066-82-6
研究领域: 组织工程 · 伤口愈合 · 生物医学材料 · 生物材料
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