Synthesis and Incorporation of Quaternary Ammonium Silane Antimicrobial into Self‐Crosslinked Type I Collagen Scaffold: A Hybrid Formulation for 3D Printing

Purpose: Plasmid loading into scaffolds to enhance sustained release of growth factors is an important focus of regenerative medicine. The aim of this study was to build gene-activated matrices (GAMs) and examine the bone augmentation properties. Methods: Generation 5 polyamidoamine dendrimers (G5 dPAMAM)/plasmid recombinant human bone morphogenetic protein-2 (rhBMP-2) complexes were immobilized into beta-tricalcium phosphate (β-TCP)/type I collagen porous scaffolds. After cultured with rat mesenchymal stem cells (rMSCs), transfection efficiencies were examined. The secretion of rhBMP-2 and alkaline phosphatase (ALP) were detected to evaluate the osteogenic properties. Scanning electron microscopy (SEM) was used to observe attachment and proliferation. Moreover, we applied these GAMs directly into freshly created segmental bone defects in rat femurs, and their osteogenic efficiencies were evaluated. Results: Released plasmid complexes were transfected into stem cells and were expressed, which caused osteogenic differentiations of rat mesenchymal stem cells (rMSCs). SEM analysis showed excellent cell attachment. Bioactivity of plasmid rhBMP-2 was maintained in vivo, and the X-ray observation, histological analysis and immunohistochemistry (IHC) of bone tissue demonstrated that the bone healing in segmental femoral defects was enhanced by implantation of GAMs. Conclusions: Such biomaterials offer therapeutic opportunities in critical-sized bone defects.

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Functional improvement following implantation of a microstructured, type-I collagen scaffold into experimental injuries of the adult rat spinal cord

Brain Research ◽

10.1016/j.brainres.2014.08.041 ◽

2014 ◽

Vol 1585 ◽

pp. 37-50 ◽

Cited By ~ 15

Author(s):

Haktan Altinova ◽

Sven Möllers ◽

Tobias Führmann ◽

Ronald Deumens ◽

Ahmet Bozkurt ◽

...

Keyword(s):

Spinal Cord ◽

Type I Collagen ◽

Collagen Scaffold ◽

Functional Improvement ◽

Type I ◽

Rat Spinal Cord ◽

Adult Rat ◽

Adult Rat Spinal Cord

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Cell-Free Scaffolds as a Monotherapy for Focal Chondral Knee Defects

Materials ◽

10.3390/ma13020306 ◽

2020 ◽

Vol 13 (2) ◽

pp. 306 ◽

Cited By ~ 3

Author(s):

Haowen Kwan ◽

Emanuele Chisari ◽

Wasim S. Khan

Keyword(s):

Articular Cartilage ◽

Type I Collagen ◽

Collagen Scaffold ◽

Cartilage Regeneration ◽

Underlying Mechanism ◽

Type I ◽

Surgical Interventions ◽

Hydrogel Scaffolds ◽

Chondral Defects ◽

The Many

Chondral knee defects have a limited ability to be repaired. Current surgical interventions have been unable to regenerate articular cartilage with the mechanical properties of native hyaline cartilage. The use of a scaffold-based approach is a potential solution. Scaffolds are often implanted with cells to stimulate cartilage regeneration, but cell-based therapies are associated with additional regulatory restrictions, an additional surgical procedure for cell harvest, time for cell expansion, and the associated costs. To overcome these disadvantages, cell-free scaffolds can be used in isolation allowing native cells to attach over time. This review discusses the optimal properties of scaffolds used for chondral defects, and the evidence for the use of hydrogel scaffolds and hydrogel–synthetic polymer hybrid scaffolds. Preclinical and clinical studies have shown that cell-free scaffolds can support articular cartilage regeneration and have the potential to treat chondral defects. However, there are very few studies in this area and, despite the many biomaterials tested in cell-based scaffolds, most cell-free studies focused on a specific type I collagen scaffold. Future studies on cell-free scaffolds should adopt the modifications made to cell-based scaffolds and replicate them in the clinical setting. More studies are also needed to understand the underlying mechanism of cell-free scaffolds.

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Collagenous Biocomposites for the Repair of Soft Tissue Injury

MRS Proceedings ◽

10.1557/proc-252-151 ◽

1991 ◽

Vol 252 ◽

Cited By ~ 2

Author(s):

David Christiansen ◽

George Pins ◽

Ming Che Wang ◽

Michael G. Dunn ◽

Frederick H. Silver

Keyword(s):

Tissue Regeneration ◽

Type I Collagen ◽

Tissue Injury ◽

Soft Tissue Injury ◽

Collagen Scaffold ◽

High Strength ◽

Tissue Scaffolds ◽

Animal Tissue ◽

Type I ◽

Tissue Models

ABSTRACTResults of implantation studies in a variety of animal tissue models demonstrate that the rate of biogradation of a collagen scaffold should parallel the rate of wound healing observed in particular anatomic sites. This rapid degradation maximizes tissue regeneration and minimizes encapsulation of the implant. The following paper reviews the effects of crosslinking on the rate of tissue ingrowth and regeneration. In addition, preliminary mechanical data on newly developed soluble type I collagen fibers is presented as a possible advance in the production of high strength collagen based tissue scaffolds.

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Type I collagen scaffold with WNT5A plasmid for in situ cartilage tissue engineering

Bio-Medical Materials and Engineering ◽

10.3233/bme-211277 ◽

2021 ◽

pp. 1-12

Author(s):

Ruo-Fu Tang ◽

Xiao-zhong Zhou ◽

Lie Niu ◽

Yi-Ying Qi

Keyword(s):

Tissue Engineering ◽

Cartilage Repair ◽

Type I Collagen ◽

Cartilage Tissue Engineering ◽

Collagen Scaffold ◽

Defect Group ◽

Cartilage Tissue ◽

Type I ◽

Type Ii ◽

Osteochondral Defects

BACKGROUND: Cartilage tissue lacks the ability to heal. Cartilage tissue engineering using cell-free scaffolds has been increasingly used in recent years. OBJECTIVE: This study describes the use of a type I collagen scaffold combined with WNT5A plasmid to promote chondrocyte proliferation and differentiation in a rabbit osteochondral defect model. METHODS: Type I collagen was extracted and fabricated into a collagen scaffold. To improve gene transfection efficiency, a cationic chitosan derivative N,N,N-trimethyl chitosan chloride (TMC) vector was used. A solution of TMC/WNT5A complexes was adsorbed to the collagen scaffold to prepare a WNT5A scaffold. Osteochondral defects were created in the femoral condyles of rabbits. The rabbits were divided into defect, scaffold, and scaffold with WNT5A groups. At 6 and 12 weeks after creation of the osteochondral defects, samples were collected from all groups for macroscopic observation and gene expression analysis. RESULTS: Samples from the defect group exhibited incomplete cartilage repair, while those from the scaffold and scaffold with WNT5A groups exhibited “preliminary cartilage” covering the defect. Cartilage regeneration was superior in the scaffold with WNT5A group compared to the scaffold group. Safranin O staining revealed more proteoglycans in the scaffold and scaffold with WNT5A groups compared to the defect group. The expression levels of aggrecan, collagen type II, and SOX9 genes were significantly higher in the scaffold with WNT5A group compared to the other two groups. CONCLUSIONS: Type I collagen scaffold showed effective adsorption and guided the three-dimensional arrangement of stem cells. WNT5A plasmid promoted cartilage repair by stimulating the expression of aggrecan, type II collagen, and SOX9 genes and proteins, as well as inhibiting cartilage hypertrophy.

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3D Printed In Vitro Dentin Model to Investigate Occlusive Agents against Tooth Sensitivity

Materials ◽

10.3390/ma14237255 ◽

2021 ◽

Vol 14 (23) ◽

pp. 7255

Author(s):

Shiva Naseri ◽

Megan E. Cooke ◽

Derek H. Rosenzweig ◽

Maryam Tabrizian

Keyword(s):

3D Printing ◽

Type I Collagen ◽

Three Dimensional ◽

Raw Material ◽

Type I ◽

Dentinal Tubule ◽

Human Teeth ◽

Tooth Sensitivity ◽

3D Printed

Tooth sensitivity is a painful and very common problem. Often stimulated by consuming hot, cold, sweet, or acidic foods, it is associated with exposed dentin microtubules that are open to dental pulp. One common treatment for tooth hypersensitivity is the application of occlusive particles to block dentin microtubules. The primary methodology currently used to test the penetration and occlusion of particles into dentin pores relies upon dentin discs cut from extracted bovine/human teeth. However, this method is limited due to low accessibility to the raw material. Thus, there is a need for an in vitro dentin model to characterize the effectiveness of occlusive agents. Three-dimensional printing technologies have emerged that make the printing of dentin-like structures possible. This study sought to develop and print a biomaterial ink that mimicked the natural composition and structure of dentin tubules. A formulation of type I collagen (Col), nanocrystalline hydroxyapatite (HAp), and alginate (Alg) was found to be suitable for the 3D printing of scaffolds. The performance of the 3D printed dentin model was compared to the natural dentin disk by image analysis via scanning electron microscopy (SEM), both pre- and post-treatment with occlusive microparticles, to evaluate the degree of dentinal tubule occlusion. The cytocompatibility of printed scaffolds was also confirmed in vitro. This is a promising biomaterial system for the 3D printing of dentin mimics.

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In VivoMagnetic Resonance Imaging of Type I Collagen Scaffold in Rat: Improving Visualization of Bladder and Subcutaneous Implants

Tissue Engineering Part C Methods ◽

10.1089/ten.tec.2014.0046 ◽

2014 ◽

Vol 20 (12) ◽

pp. 964-971 ◽

Cited By ~ 9

Author(s):

Yi Sun ◽

Paul Geutjes ◽

Egbert Oosterwijk ◽

Arend Heerschap

Keyword(s):

Type I Collagen ◽

Collagen Scaffold ◽

Type I ◽

Resonance Imaging

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PEG-Coated Large Mesoporous Silicas as Smart Platform for Protein Delivery and Their Use in a Collagen-Based Formulation for 3D Printing

International Journal of Molecular Sciences ◽

10.3390/ijms22041718 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1718

Author(s):

Federica Banche-Niclot ◽

Giorgia Montalbano ◽

Sonia Fiorilli ◽

Chiara Vitale-Brovarone

Keyword(s):

3D Printing ◽

Protein Delivery ◽

Type I Collagen ◽

Bone Matrix ◽

Collagen Matrix ◽

Mesoporous Structure ◽

Mesoporous Silicas ◽

Type I ◽

Ph Responsive ◽

Polymer Hydrolysis

Silica-based mesoporous systems have gained great interest in drug delivery applications due to their excellent biocompatibility and high loading capability. However, these materials face challenges in terms of pore-size limitations since they are characterized by nanopores ranging between 6–8 nm and thus unsuitable to host large molecular weight molecules such as proteins, enzymes and growth factors (GFs). In this work, for an application in the field of bone regeneration, large-pore mesoporous silicas (LPMSs) were developed to vehicle large biomolecules and release them under a pH stimulus. Considering bone remodeling, the proposed pH-triggered mechanism aims to mimic the release of GFs encased in the bone matrix due to bone resorption by osteoclasts (OCs) and the associated pH drop. To this aim, LPMSs were prepared by using 1,3,5-trimethyl benzene (TMB) as a swelling agent and the synthesis solution was hydrothermally treated and the influence of different process temperatures and durations on the resulting mesostructure was investigated. The synthesized particles exhibited a cage-like mesoporous structure with accessible pores of diameter up to 23 nm. LPMSs produced at 140 °C for 24 h showed the best compromise in terms of specific surface area, pores size and shape and hence, were selected for further experiments. Horseradish peroxidase (HRP) was used as model protein to evaluate the ability of the LPMSs to adsorb and release large biomolecules. After HRP-loading, LPMSs were coated with a pH-responsive polymer, poly(ethylene glycol) (PEG), allowing the release of the incorporated biomolecules in response to a pH decrease, in an attempt to mimic GFs release in bone under the acidic pH generated by the resorption activity of OCs. The reported results proved that PEG-coated carriers released HRP more quickly in an acidic environment, due to the protonation of PEG at low pH that catalyzes polymer hydrolysis reaction. Our findings indicate that LPMSs could be used as carriers to deliver large biomolecules and prove the effectiveness of PEG as pH-responsive coating. Finally, as proof of concept, a collagen-based suspension was obtained by incorporating PEG-coated LPMS carriers into a type I collagen matrix with the aim of designing a hybrid formulation for 3D-printing of bone scaffolds.

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Engineered human meniscus’ matrix-forming phenotype is unaffected by low strain dynamic compression under hypoxic conditions

PLoS ONE ◽

10.1371/journal.pone.0248292 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0248292

Author(s):

Alexander R. A. Szojka ◽

Colleen N. Moore ◽

Yan Liang ◽

Stephen H. J. Andrews ◽

Melanie Kunze ◽

...

Keyword(s):

Mechanical Properties ◽

Type I Collagen ◽

Dynamic Compression ◽

Collagen Scaffold ◽

Specific Protein ◽

Type I ◽

Low Oxygen ◽

Hypoxic Conditions ◽

Mrna Markers ◽

Hypoxia Treatment

Low oxygen and mechanical loading may play roles in regulating the fibrocartilaginous phenotype of the human inner meniscus, but their combination in engineered tissues remains unstudied. Here, we investigated how continuous low oxygen (“hypoxia”) combined with dynamic compression would affect the fibrocartilaginous “inner meniscus-like” matrix-forming phenotype of human meniscus fibrochondrocytes (MFCs) in a porous type I collagen scaffold. Freshly-seeded MFC scaffolds were cultured for 4 weeks in either 3 or 20% O2 or pre-cultured for 2 weeks in 3% O2 and then dynamically compressed for 2 weeks (10% strain, 1 Hz, 1 h/day, 5 days/week), all with or without TGF-β3 supplementation. TGF-β3 supplementation was found necessary to induce matrix formation by MFCs in the collagen scaffold regardless of oxygen tension and application of the dynamic compression loading regime. Neither hypoxia under static culture nor hypoxia combined with dynamic compression had significant effects on expression of specific protein and mRNA markers for the fibrocartilaginous matrix-forming phenotype. Mechanical properties significantly increased over the two-week loading period but were not different between static and dynamic-loaded tissues after the loading period. These findings indicate that 3% O2 applied immediately after scaffold seeding and dynamic compression to 10% strain do not affect the fibrocartilaginous matrix-forming phenotype of human MFCs in this type I collagen scaffold. It is possible that a delayed hypoxia treatment and an optimized pre-culture period and loading regime combination would have led to different outcomes.

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