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Collagen is the most abundant natural protein found in living systems. While there is a whole family of different collagen types, each differing in sequence, the properties that make this protein so attractive as the building blocks for medical devices, are reflected largely by the unique fibrillar structure of the molecule, as well as defined functional regions that interact with the surrounding cells and other matrix components. As a commercial medical product, collagen can be part of the natural tissue used in the device, or it can be fabricated as a reconstituted product from animal or recombinant sources. Both types of uses have distinct properties that convey advantages and disadvantages to the end product. This review examines the chemistry and biology of collagen and describes some well-documented examples of collagen-based medical devices produced in one or other of these formats.

The interaction between cells and biomaterials strongly depends on the assembled structure of collagen adsorption upon the solid surface. Due to its self-assembling property, Type I collagen may aggregate and form fibrils in vivo and in vitro. This study utilizes an atomic force microscope to investigate nanometer-scale organization of adsorbed Type I collagen layers on mica and on poly(methyl methacrylate) (PMMA). We have observed various film morphologies, depending on substrate hydrophobicity and the state of collagen solution used. On mica, the atomic force microscopy (AFM) study obtains dense felt-like structures of randomly distributed assemblies. Images of network-like assemblies composed of interwoven fibrils appear on PMMA. According to the above results, we believe that these assemblies are associated at the interface rather than aggregated in the solution. This work also investigates the adsorbed collagen structure on PMMA after collagen aggregation in solution, to realize the relation between adsorption and aggregation. Consequently, the result exhibits a dendritic fibrillar structure adsorbed on PMMA, following collagen molecule aggregation, to form a fibrillar structure in the solution. This result suggests that the adsorption of aggregates preformed in the solution is preferable to collagen molecules adsorption. This research created all assembled structures of adsorbed collagen layers in nanometer-scale thickness.

Developments on tissue engineering, especially on tissue regeneration and drug delivery, demand also developments on biomaterials. Research on the preparation methods of biomaterials has exhibited remarkable advances in the recent years. Natural biomaterials, such as chitosan and collagen, or synthetic materials like poly(lactic acid) can be shaped in various forms. The parameters involved in the fabrication processes provide methodologies for control of the materials' properties, such as morphology, biodegradability, mechanical strength, and adhesion. As new applications develop for these materials, the preparation methods have to be optimized to achieve the desired material properties. These properties mostly not only mimic the conditions in the human body, but also may divert the microenvironment of cells in the diseased area in order to promote faster or guided healing and tissue regeneration. This review pays attention on some of the fabrication methods for biomaterial particulates of sizes in the micro- and nanoscale. The views expressed here focus on the many years of experience of the authors with electrostatic and ultrasonic fabrication methods. These methods are still under development and up to now can produce particulates of various sizes down to the nanometer scale with narrow size distributions. Such biomaterials that have extraordinary properties may provide ways for the development of remarkable biomedical applications.

Injectable filler, which is often applied in minimally invasive surgery, has been widely-used in facial rejuvenation. Because of its convenience, effective usage and less downtime after treatment for the patients, it becomes one of the most popular treatment methods at present. The currently available products containing collagen base have been proven to have much satisfactory safety and effectiveness, but one of its disadvantages is the lack of long-term volume persistence. We have previously prepared the reconstituted collagen fibrils with hyaluronic acid (HA) by modifying the fibril surface. This study is to evaluate the potential of these materials as injectable filler in vitro. A preparation of collagen fibrils with a diameter of 100–150 nm was used. The modification rate of HA on the fibril surface was 20%. In assessment of the biocompatibility, it was proven that the collagen fibril and HA-collagen fibril treated with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) had no cytotoxicity or inhibitory actions. In interactions between these materials and cells, it was found that the existence of HA could improve the migration ability of L929 fibroblasts and breast cancer cells (MDA-MB 435s). In conclusion, collagen fibril and HA-collagen fibril have the potential to be developed into an injection as a soft tissue filler for biomedical applications.

Hydroxyapatite (HAp) is the major inorganic component in human bones and well known for its biocompatibility. It has been widely prepared in many forms for orthopedic and dental applications. Color-center-doped HAps are also prevalently used as fluorescent materials. Further, HAp based photoluminescent material might be an ideal agent for bioimaging. Moreover, self-assembly of HAp in calcium- and phosphate-containing solutions gains a lot of attention because organic–inorganic HAp hybrids can be tailor-made. In this study, the author used a biomimetic process to synthesize organic–inorganic HAp nano hybrid at room temperature. The natural and synthesized polymeric templates used to prepare the organic–inorganic HAp hybrids were collagen, PEG–PLGA (di block), and PEG–PLGA–PEG (tri block), respectively. X-ray diffraction (XRD) diagrams revealed that the synthesized powders had crystalline HAp phase, and transmission electron microscope (TEM) photographs showed their nano grain structure. Characterization using XRD, TEM, and Fourier transform infrared spectrometer (FTR) indicated the existence of crystalline HAp phase and the variation in HAp shape versus different polymers in the composite powders. The measurement of photoluminescent (PL) spectra used a 325 nm He–Cd laser as source. The di HAp and tri HAp emitted light with a wide range of wavelength from 350 to 550 nm, much stronger than pure HAp. Collagen alone emitted brighter fluorescence peaked around 410 nm but was quickly quenched, while collagen–HAp composite powders emitted sustaining PL light peaking around 415 nm. The developed PL bioceramics are of great potential in bio sensing and bio optoelectronics.

In this work, we used multiphoton microscopic system for characterizing three-dimensional microstructure of collagen/chitosan polymeric scaffolds in a noninvasive fashion. Nonlinear optical signals including multiphoton autofluorescence (MAF) and second harmonic generation (SHG) derived from collagen/chitosan scaffolds were collected and analyzed. The three-dimensional porous microstructures of collagen/chitosan scaffolds were visualized by co-localized and evenly distributed MAF and SHG signals. The distribution of collagen and chitosan compositions within miscible collagen/chitosan blends cannot be either localized or differentiated simply using these nonlinear optical signals. However, the intensity of MAF signals in scaffolds was found to be markedly decreased in correlation to the supplementation of chitosan within blends, regardless of collagen/chitosan weight ratios. It therefore implied that the MAF-generating molecules within collagen being altered in miscible collagen/chitosan blends. And the SHG signals also decreased significantly in collagen/chitosan scaffolds with the supplementation of chitosan, regardless of different weight ratios. This finding supported the hypothesis regarding the miscibility of collagen/chitosan blends that triple helix structure of collagen, a proven SHG-generating microstructure, was altered in miscible collagen/chitosan blends. In conclusion, our work demonstrated that multiphoton imaging modality can be versatile for investigating three-dimensional microstructure of miscible polymeric scaffolds in a minimal invasive fashion, and may potentially be applicable in the field of tissue engineering.

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.

Collagen and noncollagenous proteins have an important role in the formation of mineral constituent of bone matrix. In this research, the morphology and phase characteristics of calcium phosphate nanoparticles in presence of collagen were investigated. The synthesis reaction was initiated by mixing H₃PO₄ as phosphorous source and CaCl₂ as calcium source and type I collagen. Collagen concentration in suspension and Ca to P ratio was 1% and 1.67, respectively. The samples (with collagen and without collagen), were heat treated at 600°C and characterized by X-Ray diffraction (XRD), Fourier transformation infrared (FTIR) and scanning electron microscopy (SEM). More smaller and flake-like shape particles were observed in the SEM images of sample synthesized in the presence of collagen compared to the control sample which was constituted of larger granular particles. The XRD results revealed that the synthesized mineral powders with collagen were composed of hydroxyapatite and octacalcium phosphate. P–O and OH characteristic peaks were identified in FTIR spectra. In hybrid sample, the shift of amides band, revealed the electrostatic interactions between calcium phosphate ions and carboxyl or amino groups of collagen fibrils. The Ca to P molar ratio for sample with collagen was 1.9. It was found that the sample synthesized in the presence of collagen has a similar microstructure to natural bone.

Background and aim: Healing of fire-induced wounds has been still a challenge in clinical issues. The aim of this study was to fabricate a nanofibrous poly (L-lactic acid)/collagen (PLLA/COL) scaffold with sustained release of aloe vera (AV) gel using a chitosan (CT)-coated layer for skin tissue engineering applications. Material and methods: Morphology, porosity, tensile strength, hydrophilicity, degradation rate, water vapor permeability and water uptake ratio of the scaffold were characterized. The behaviors of mouse fibroblasts (L929) were evaluated on the scaffold. Results: We observed that although the porosity of the scaffold was decreased, other characteristics were enhanced by coating a CT layer. The scaffold supports attachment, viability and proliferation of mouse fibroblasts. Conclusion: Consequently, the PLLA/COL scaffold coated with CT for sustained release of AV gel can be considered as a desirable scaffold for skin tissue engineering.