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Collagen-Based Biomaterials for Tissue Engineering Applications

Rémi Parenteau-Bareil
Robert Gauvin
1,2 and
François Berthod
Laboratoire d’Organogénèse Expérimentale (LOEX), Centre de recherche FRSQ du CHA universitaire de Québec, Hôpital du Saint-Sacrement, Québec, QC, G1S 4L8 Canada
Département de chirurgie, Faculté de médecine, Université Laval, Québec, QC, G1V 0A6 Canada
Author to whom correspondence should be addressed.
Materials 2010, 3(3), 1863-1887;
Submission received: 2 February 2010 / Revised: 9 March 2010 / Accepted: 11 March 2010 / Published: 16 March 2010
(This article belongs to the Special Issue Advances in Biomaterials)


Collagen is the most widely distributed class of proteins in the human body. The use of collagen-based biomaterials in the field of tissue engineering applications has been intensively growing over the past decades. Multiple cross-linking methods were investigated and different combinations with other biopolymers were explored in order to improve tissue function. Collagen possesses a major advantage in being biodegradable, biocompatible, easily available and highly versatile. However, since collagen is a protein, it remains difficult to sterilize without alterations to its structure. This review presents a comprehensive overview of the various applications of collagen-based biomaterials developed for tissue engineering, aimed at providing a functional material for use in regenerative medicine from the laboratory bench to the patient bedside.

1. Introduction

During the past decade, numerous innovations occurred in the field of collagen-based biomaterials. From injectable collagen matrices to bone regeneration scaffolds, production and cross-linking methods have evolved and improved. Collagen is now widely used in both research environments and medical applications. A brief introduction of the collagen molecule will be presented, followed by some technical explanation covering collagen scaffold production methods. Ultimately, the recent advances that have been developed in collagen-based tissue-engineering biomaterials will be discussed.

2. The Collagen Molecule

2.1. Distribution, biosynthesis and molecular structure

The presence of collagen in all connective tissue makes it one the most studied biomolecules of the extracellular matrix (ECM). This fibrous protein species is the major component of skin and bone and represents approximately 25% of the total dry weight of mammals [1]. To this day, 29 distinct collagen types have been characterized and all display a typical triple helix structure. Collagen types I, II, III, V and XI are known to form collagen fibers. Collagen molecules are comprised of three α chains that assemble together due to their molecular structure. Every α chain is composed of more than a thousand amino acids based on the sequence -Gly-X-Y-. The presence of glycine is essential at every third amino acid position in order to allow for a tight packaging of the three α chains in the tropocollagen molecule and the X and Y positions are mostly filled by proline and 4-hydroxyproline [2,3].
There are approximately twenty-five different α chain conformations, each produced by their unique gene. The combination of these chains, in sets of three, assembles to form the twenty-nine different types of collagen currently known. The most common are briefly described in Table 1. Although many types of collagen have been described, only a few types are used to produce collagen-based biomaterials. Type I collagen is currently the gold standard in the field of tissue-engineering.
The fibroblast is responsible for the majority of the collagen production in connective tissue. Collagen pro-α chain is synthesized from a unique mRNA within the rough endoplasmic reticulum and is then transferred to the Golgi apparatus of the cell. During this transfer, some prolines and lysines residues are hydroxylated by the lysyl oxydase enzyme. Specific lysines are glycosylated and then pro-α chains self-assemble into procollagen prior to their encapsulation in excretory vesicles. Following their passage through the plasma membrane, the propeptides are cleaved outside the cell to allow for the auto-polymerisation by telopeptides. This step marks the initiation of tropocollagen self-assembly into 10 to 300 nm sized fibril and the agglomeration of fibril into 0.5 to 3 μm collagen fibers, see Figure 1 [1]. Fibril-forming collagens are the most commonly used in the production of collagen-based biomaterials.
Table 1. Collagen types, forms and distribution. Modified from [1].
Table 1. Collagen types, forms and distribution. Modified from [1].
TypeMolecular formulaPolymerized formTissue distribution
Fibril-Forming (fibrillar)I [α1(I)]2α2(I)fibrilbone, skin, tendons, ligaments, cornea (represent 90% of total collagen of the human body)
II [α1(II)]3fibrilcartilage, intervertebrate disc, notochord, vitreous humor in the eye
III [α1(III)]3fibrilskin, blood vessels
V [α1(V)]2α2(V) and α1(V)α2(V)α3(V)fibril (assemble with type I)idem as type I
XIα1(XI)α2(XI)α3(XI)fibril (assemble with type II)idem as type II
Fibril-associatedIXα1(IX)α2(IX)α3(IX)lateral association with type II fibrilcartilage
XII [α1(XII)]3lateral association with type I fibriltendons, ligaments
Network-formingIV [α1(IV)]2α2(IV)Sheet-like networkbasal lamina
VII [α1(VII)]3anchoring fibrilsbeneath stratified squamous epithelia
Figure 1. (a) Schematization of a collagen α chain triple helix segment. (b) Assembled tropocollagen molecules. (c) Collagen fibril ranging from 10 to 300 nm in diameter. (d) Aggregated collagen fibrils forming a collagen fiber with a diameter ranging from 0.5 to 3 μm.
Figure 1. (a) Schematization of a collagen α chain triple helix segment. (b) Assembled tropocollagen molecules. (c) Collagen fibril ranging from 10 to 300 nm in diameter. (d) Aggregated collagen fibrils forming a collagen fiber with a diameter ranging from 0.5 to 3 μm.
Materials 03 01863 g001

2.2. Immunogenicity and biocompatibility

The use of biological material for medical applications requires making a distinction between immunogenicity and antigenicity. Immunogenicity is about triggering an immune response while antigenicity refers to the interaction between the antibodies and the antigenic determinants or epitopes [4]. An immune response against collagen mainly targets epitopes in the telopeptide region at each end of the tropocollagen molecule [5,6,7]. However, the conformation of the helical part and the amino acid sequence on the surface of the polymerized collagen fibril, also influence the immunologic profile of the collagen molecule [8,9,10,11,12]. Thus, the difference of immunogenicity between polymerized collagen and their smaller counterpart lies on the accessibility of the antigenic determinants that decrease during the polymerisation process [13,14].
Type I collagen is a suitable material for implantation since only a small amount of people possess humoral immunity against it and a simple serologic test can verify if a patient is susceptible to an allergic reaction in response to this collagen-based biomaterial [15,16].
It is important to mention that these facts about collagen immunogenicity are also applicable to collagen molecules comprised of an acellular ECM and that most adverse immune responses that have been encountered with an acellular scaffold are not necessarily originating from the collagen molecule itself. Incomplete decellularization resulting in residual oligosaccharide α-Gal or DNA is most often the cause of acellular ECM rejection or acute immune responses [17].

2.3. Collagen origin and variability

Collagen can be extracted from various sources considering that it is one of the most abundant proteins on earth. It can be extracted from almost every living animal, even including alligators [18] and kangaroos [19]. Nonetheless, common sources of collagen for tissue engineering applications include bovine skin and tendons, porcine skin and rat tail among others. Marine life forms are also a considerable source of collagen, which can be extracted from sponges [20,21], fish [22] and jellyfish [23]. These collagens are widely used in the industry, but less for research and clinical usage. All these collagen sources are worth investigating considering that collagen properties differ from one animal to another [24]. However, the company Fibrogen® distributes recombinant human collagen since 2004 that is potentially less immunogenic than animal sources but more importantly is identical in composition for different production lots and appears to be the future of collagen scaffolds [25]. Collagen can also be used in biomedical applications as a decellularized ECM serving as a scaffolding material for tissue regeneration. Although extractible from many different sources, the diversity of acellular collagen scaffolds are quite restraint due to immunological, physical scaffold size and availability aspects. Thus, acellular ECM are typically produced from human or porcine dermis or from swine intestine or bladder submucosa (SIS or BSM) [26].

2.4. Biodegradability and collagenases

Biodegradability is a valuable aspect for most collagen-based biomaterials. Collagen biocompatibility and possible degradation by human collagenases are responsible for the widespread use of this material in many biomedical applications. On the other hand, the rate of the degradation process often needs to be regulated using diverse methods such as crosslinking techniques [13,14] or a structural modification agent like Epigallocatechin-3-gallate (EGCG) [27]. Therefore, biodegradation of collagen-based biomaterials for applications such as tissue engineering could potentially lead to the restoration of tissue structure and functionality [28]. In addition, the degradation product of collagen type I to III have also been shown to induce a chemotactic attraction of human fibroblasts [29].
Collagenases such as matrix metalloproteinase (MMP) are responsible for most collagen degradation in vivo. It is also important to know that all collagenases have a different rate of collagen hydrolysis. Mammalian collagenases such as MMP-1, MMP-2, MMP-8, MMP-13 and MMP-14 have the capacity to hydrolyze collagen type I to III [30,31,32,33,34,35], while some other like MMP-3 and MMP-9 bind to type I collagen but do not degrade the native tropocollagen molecule [36,37,38]. The collagenolytic activity of all these MMP rely on three principles: the ability to bind collagen molecules, the ability to unwind the three α chains and the ability to cleave each strand of the triple helix [39]. These parameters are also of concern when it comes to bacterial collagenases or non-specific proteolytic enzymes such as C. histolyticum collagenase or trypsin.

2.5. Collagen and cellular interactions

Collagen is a key structural element of vertebrate evolution. The path that led to complex life form, like human being, relies on three types of interactions. In 1985, Ruoslahti et al. stated that relation between cells and ECM are based on self-aggregation of matrix molecules, on interaction of these aggregated molecules with one another and finally on their affinity toward cell surface to allow cells binding to the ECM as well as proliferation [40]. Cell-matrix interactions imply mostly interaction of cells with collagen, directly or indirectly. Direct cell-collagen interactions imply cell receptors that recognize specific peptide sequence within collagen molecules. These receptors are divided into four groups. The receptors of the first group, like glycoprotein VI, recognize peptide sequence containing GPO motif (Gly-Pro-Hyp) [41]. The second group is composed of collagen binding receptor members of integrin family and discoidin domain receptor 1 and 2 (DDR1 and DDR2). All these receptors bind to different specific motifs often including a GFO (Gly-Phe-Hyp) sequence [42,43,44]. The third group of collagen binding receptor are integrin-types that recognize cryptic motifs within the collagen molecule [45]. Finally the other cell receptors that directly bind collagen have affinity for the non-collagenous domain of the molecule. The two last groups of collagen binding receptors normally imply other cell-matrix interactions via indirect cell-collagen interactions to achieve stable adhesion of cell to the ECM. One of the key molecules of indirect cell-collagen interactions is fibronectin, on which the integrin recognized sequence RGD (Arg-Gly-Asp) was first identified [46,47]. A lot of proteins containing RGD or similar motifs recognized by integrin also bind to collagen, thus allowing indirect cell-collagen interactions. Proteins like decorin and laminin can bind either collagen and integrin promoting cell adhesion and proliferation [48]. Those facts about collagen receptors and collagen binding molecule are of important concern for the choice of collagen or ECM source to produce collagen-based biomaterials. This is why the treatments used to extract collagen, to decellularized ECM or to sterilized biomaterials are of outmost importance. Furthermore, the molecular architecture of collagen and other associated proteins in biomaterials are crucial for seeded cell adhesion, migration and in some case differentiation.

3. Collagen-Based Biomaterials

3.1. Types of collagen-based biomaterials

Collagen-based biomaterials can originate from two fundamental techniques. The first one is a decellularized collagen matrix preserving the original tissue shape and ECM structure, while the other relies on extraction, purification and polymerization of collagen and its diverse components to form a functional scaffold. Both techniques can be submitted to various cross-linking methods and protocols which are applicable to a wide variety of tissue sources and species of origin.
Many techniques can lead to the production of an acellular collagen matrix or ECM. Gilbert, Sellaro and Badylak have elegantly reviewed the three method used for tissue decellularization: physical, chemical and enzymatic [49]. Physical methods include snap freezing that disrupt cells by forming ice crystals, high pressure that burst cells and agitation, that induce cell lysis and used most often in combination with chemical methods to facilitate penetration of active molecules in the tissue. Chemical methods of decellularization include a variety of reagents that can be use to remove the cellular content of ECM. These substances range from acid to alkaline treatments, as well as chelating agents such as EDTA, ionic or non-ionic detergents and solutions of extreme osmolarity. Enzymatic treatments such as trypsin, which specifically cleaves proteins and nucleases that remove DNA and RNA are also commonly used to produce acellular scaffold. However, none of these methods can produce an ECM completely free of cellular debris and a combination of techniques is often required to obtain a material free of any cell remnant.
The other type of collagen-based biomaterial is made by processing a collagen solution with other biomolecules like glycosaminoglycans (GAG) [50,51,52], elastin [53,54,55] or chitosan [56,57,58]. In order to produce collagen-based biomaterials, different approaches were developed to extract collagen from biological tissues. Modern extraction methods are based on three basic principles of solubilisation: in acid solutions [59,60], in neutral salt solutions [61,62] and in proteolytic solutions [63,64,65]. Proteolytic extraction however, alters collagen molecular structure by cleaving the terminal telopeptide regions and results in a proportional decrease in tropocollagen self-assembled fibrils [66]. To avoid this effect endogenous proteases can be inhibited during the acid solubilization [67]. Nonetheless, the acid extraction using a slight pepsin solubilization, is the most effective technique in terms of yield, albeit some telopeptides are cleaved or partially denaturated [67,68].

3.2. Crosslinking methods and reinforcement with biopolymers combination

Crosslinking techniques are especially important for collagen-based biomaterials when compared to acellular collagen matrices that have already been polymerized in vivo. As previously stated, the two types of collagen-based biomaterials can be crosslinked in order to enhance their mechanical and enzymatic resistance properties for implantation purposes. The principle of a cross-linking reaction relies on the modification of amine and carboxyl groups within the collagen molecules, to allow the formation of covalent bonds. Several methods have been developed to cross-link collagen scaffolds. These polymerization techniques are distributed among three types: physical, chemical and enzymatic crosslinking.
Physical crosslinking rely on irradiation by ultra-violet wavelengths (UV) or thermal sources to induce the collagen scaffold polymerization. UV irradiation and dehydrothermal (DHT) treatment produce similar results when used to crosslink collagen scaffolds. Both techniques induce an increase in tensile strength and some fragmentation in the collagen molecular structure [69]. However, UV irradiation is more time-effective when compared to DHT treatment as it takes only 15 minutes instead of 3 to 5 days for the DHT treatment. UV crosslinked collagen scaffolds also result in a more suitable biomaterial for load-bearing applications due to its enhanced enzymatic resistance [13]. Besides, UV irradiation has been recently optimized to reduced collagen fragmentation by using glucose in the crosslinking process [70]. However, UV irradiation is only effective for thin and/or transparent scaffolds, allowing UV to go through the structure.
The chemical techniques used to crosslink collagen-based biomaterial are more diversified. The use of aldehydes such as formaldehyde and glutaraldehyde was extensively used in the past decade. Glutaraldehyde is the most employed and studied chemical method used to crosslink collagen-based biomaterials [14,58,71,72]. Another class of chemicals used to enhance mechanical and enzymatic resistance of a collagen scaffold is the carbodiimide family [73,74,75,76]. These chemicals can also be used to crosslink collagen to some marginal substances like gold nanostructure [77] or utilized in combination with epoxy [78,79]. The isocyanate chemical family, especially hexamethylene diisocyanate, is also used to crosslink collagen scaffolds [80,81]. The commercially available product Zimmer® Collagen Repair Patch currently uses a proprietary isocyanate crosslinking technique. Genipin, a chemical cross-linker derived from a vegetal source, shows an interesting potential to replace glutaraldehyde because of its low toxicity [82,83]. However, all these chemical stabilisation techniques leave potentially toxic residues in the collagen-based biomaterial [84,85].
An alternative to covalent bond crosslinking is to promote the formation of ionic bonds between collagen molecules. This can be achieved by polycationic molecules such as chitosan, which create ionic bonds between its numerous amine groups and the carboxyl groups of collagen. These bonds are strong enough to stabilize the biomaterial structure and form a strong mechanical strength [57,86]. The major advantage of this technique is to prepare the biomaterial in a one step process, where chitosan is mixed with collagen before freeze-drying, avoiding the need of further washing steps since chitosan is not toxic [87].
Finally, enzymatic crosslinking agents like transglutaminase can be used to enhance tensile strength and enzymatic resistance of collagen-based biomaterial [55,88,89]. The major advantage with the approach of using a biologic polymerization technique is that no chemical residues or by-products remain in the scaffold structure, and therefore eliminate the risk of inducing cytotoxic effects.
A plethora of biomolecules can also be added to collagen solution to produce collagen-based biomaterials. These biomolecules, typically GAG, elastin and chitosan are added to the compound to potentially enhance the mechanical strength and to modulate cellular functions such as migration, proliferation and differentiation [90,91,92,93,94,95,96].

3.3. Sterilisation methods

The structure of collagen scaffolds, either crosslinked or decellularized, is relatively fragile and is temperature sensitive. Therefore, they are not autoclavable and require an alternate specific sterilization process prior to their use. Even if some sterilization of collagen-based biomaterials is done by low dose gamma irradiation (γ-ray), this method alters molecular structure and decreases mechanical and enzymatic resistance of the collagen scaffold [19,97,98,99]. The addition of glucose during irradiation has been investigated to increase sterilized scaffold tensile strength by forming glucose crosslinking, but does not avoid collagen structure degradation [100]. Ethylene oxide (ETO) sterilization or β-ray irradiation are less damageable than γ-ray but their applicability depends on the type of collagen-based biomaterials produced [86,101,102]. Electron beam irradiation, like γ-ray, induces a scaffold degradation that result in the lost of mechanical and enzymatic resistance [86,103]. Immersion in a low concentration of peracetic acid is the most commonly used method to sterilize acellular collagen ECM [104] and it has been demonstrated that formic acid can also be a potential sterilization agent for collagen [105]. Ethanol immersion with the combination of fungicide and antibiotic use are techniques used in the laboratory to sterilize collagen scaffolds which have been physically crosslinked [106,107]. Anyhow, no perfect sterilization technique have been recognized for use in collagen scaffolds without any molecular alteration to its structure. Investigating the sterilization effects on collagen material properties remains the best way to assess the performance of sterilized collagen-based biomaterials [108].

4. Recent Advances in Collagen-Based Biomaterials

4.1. Experimental applications

The use of collagen-based biomaterials, from either acellular matrix or extracted collagen, in fundamental studies have a vast range of applications both in vivo and in vitro. Research groups use collagen scaffolds to study cell behavior such as migration and proliferation, as well as differentiation and phenotype expression. Moreover, fundamental findings about how cells behave in complex environments rely on the capacity of cells to grow in vitro in a 3D tissue-like scaffold. Collagen hydrogels are also convenient scaffolds when the access to cell membrane is needed, for example in electrophysiological protocols [109,110,111]. Other collagen-based scaffolds are used as nervous system models to visualise motor neuron myelinisation by Schwann cells [112]. Cancer studies are also an important research topic where 3D collagen scaffolds are useful. In this way, the invasive character of cancer cells [113,114] and interaction between cancer cells and other cell types in a 3D environment can be analysed [115]. This kind of scaffold can also be used as a 3D environment to test anticancer drugs [116]. In the domain of immunology, in vitro 3D experiments can also be done to evaluate T cell migration mechanisms [117,118]. Furthermore, collagen-based biomaterials could serve as anchorage material to cultivate organs ex vivo [119] or as 3D models for diseases like osteoarthritis [120].

4.2. Osteochondral defects

Bone and cartilage reconstruction are important topics of modern medicine either for functional or esthetic surgery. Collagen-based biomaterial implantation is necessary when osteochondral defectS reach an important volume or when autograft have to be avoided for practical or pathological reasons. Scaffolds for bone tissue engineering rely on hardening of a collagen biomaterial by mineralization with calcium phosphate [121,122] and/or on crosslinking with other substances like hydroxyapatite [123,124,125] or bushite [126,127]. Collagen-based biomaterials used for cartilage regeneration tend to be more flexible and are ideally built with type II collagen in contrast to most of the other collagen-based biomaterials, which are produced using type I collagen. Nonetheless, some studies demonstrate that small amounts of autologous chondrocytes can grow in dynamic culture on type I or II collagen structures without any notable difference [128,129]. Sheet-like collagen scaffolds seeded with or without autologous cells can also be used to fill ostechondral defects [130,131,132,133]. Further developments aimed at differentiating mesenchymal stem cells directly in collagen-based biomaterial, to permanently solve osteochondral defects on a long-term basis, are currently under investigation [134]. Optimization of pore size and distribution is also a concern considering the effect of these parameters on cell adhesion, proliferation and migration [135]. Decellularization of complex structures like meniscus has also shown promising results in order to produce an optimal replacement scaffold for specific osteochondral defects [136,137].

4.3. Vascular diseases

Two main problems arise in the domain of vascular diseases: cardiovascular malfunction and venous or arterial pathologies such as atherosclerosis. In the case of heart diseases, tissue engineering solutions rely principally on acellular matrix colonization and implantation due to the complex structural architecture of the heart like heart valves [138,139]. However, the usefulness of xenogenic acellular heart valves remain an issue due to their important immunogenic potential and tendency to become calcified [140]. This immunologic issue led to the development of commercially available human acellular scaffolds for cardiac and vascular reconstructive surgeries, i.e. Cryolife® that offers tissue replacement ranging from heart valves to vascular conduits [141,142,143]. Recent findings about complete heart decellularization by perfusion [144] and production of functional re-endothelialized veins and valves from human vein matrix [145] will certainly lead to the development of very important advances in cardiovascular regenerative medicine using collagen-based biomaterials.
A very innovative personalized medicine approach, to reconstruct living tissue-enginneered blood vessels using the patient’s own cells, has been developed at the LOEX by the group of Auger et al. [146]. The idea is to let human fibroblasts produce their own collagen-made extracellular matrix through long-term culture. This self-assembled fibroblast sheet can then be rolled around a tubular support to produce a living vessel with very impressive mechanical strength and biological properties after in vitro maturation [146,147,148]. This tissue-engineered blood vessel has been successfully grafted on patients [149,150].

4.4. Skin and cornea

Skin and cornea share a similar tissue structure: dermis and stroma both being connective tissues; epidermis and cornea being stratified epithelia. Collagen-based wound dressings have been applied for decades for burn coverage applications and ulcer treatment [28,151,152]. Highly sophisticated and innovative tissue-engineered skin models have been developed with melanocytes [153], a capillary-like network [154], dendritic cells [155], sensory innervation [94,156], adipose tissue [157], and tissue reproducing psoriatic or sclerotic phenotypes [158,159]. A living allogenic reconstructed skin (Apligraf®), made of a collagen gel-populated fibroblasts overlayed by an epidermis, is commercialized for ulcer treatment as a temporary dressing [160,161]. Skin, dermal substitutes and dressing such as Integra® (acellular collagen-GAG scaffold), Alloderm (human dermis), Amniograph (amniotic membrane) and Oasis (porcine SIS) are currently available for medical applications. Mesenchymal stem cell delivery to the wound bed in collagen-based biomaterial is a growing topic in wound healing [157,162,163,164]. The combination of collagenous biomaterials and stem cells could also be a valuable strategy to treat corneal defects. In the last decade, collagen scaffolds have been intensively studied for the delivery of limbal epithelial stem cells to damaged cornea [165,166,167,168,169,170]. Advances in collagen-based corneal scaffolds also include the utilization of recombinant human collagen [169,171,172,173], the secretion of collagen by the fibroblasts themselves (self-assembled fibroblasts sheets) [174] and surface modification to reduce extensive endothelialization [175].

4.5. Urogenital system

The use of collagen-based biomaterials in the domain of urogenital diseases and dysfunctions rely principally on acellular ECM from either SIS or BSM. These scaffolds have been extensively used to replace the enterocystoplasty and gastrocystoplasty techniques that were previously used with frequent complications [176,177]. Hence, more recent surgical procedures aiming to solve genitourinary disorders use acellular collagen scaffolds in bladder augmentation [178,179,180,181] and urethral stricture [182,183,184]. Although acellular matrix is currently evolving and slowly becoming the new gold standard for these surgeries, collagen-composite scaffolds populated with the patient’s own urothelial and muscle cells or self-assembled fibroblast sheets are also a promising strategy for bladder augmentation [185,186,187] and are showing optimistic clinical results [186]. Vesico-urethral reflux and incontinence are other defects of the urogenital system which can also be solved using injection of collagen biomaterials [188,189,190].

4.6. Neural migration

Peripheral nerve regeneration is a very important topic in regenerative medicine. Collagen-based biomaterials have been extensively studied as a promising nerve guide [191,192,193]. Multiple compositions of collagen-based nerve conduits have recently been tested with positive results compared to clinically used autografts. Even if acellular scaffolds have shown good results [194], most collagen nerve guides are engineered from crosslinked collagen solution molded into tubular shape like commercially available NeuraGen® from Integra. Pore orientation [195,196], addition of neurotrophic factors [197,198] and cell delivery [199,200,201] are currently being investigated in an attempt to enhanced nerve guides for clinical applications. Collagen-based biomaterials can also be used to develop innovative three-dimensional tissue-engineered nervous system models to promote 3D axonal migration and myelination of sensory or motor neurons by Schwann cells through a connective tissue [107,112,202].

4.7. Dermal filler, wound dressing and delivery systems

FDA approved dermal filler commonly used in facial rejuvenation or reconstructive surgery is using collagen from three distinct sources: Bovine Zyderm®, porcine Evolence™, human CosmoDerm® and Cymetra® [203,204]. Although other collagen-based biomaterials are available for this purpose [205], these products can be useful for medical office-based interventions. The overgrowing popularity for these collagen-based dermal fillers is also due to the long-term side effect observed with non-degradable fillers like Bio-Alcamid, which are susceptible to form granulomas [206,207].
Wound dressings that are also delivery systems represent an interesting application for collagen-based applications. Recent studies have shown the feasibility and more importantly the benefits of implants delivering antibiotics [208,209,210,211]. The delivery properties of collagen-based biomaterials also display great potential for ulcer treatment [197] and abdominal wall defect reconstruction [212,213,214]. Collagen scaffolds have also shown to accurately deliver cells, proteins, drugs and nucleic acids on a predictable and long-term basis [129,215,216,217]. Finally, a recent clinical trial using adenovirus in collagen gel has cleared the path for future clinical studies on gene therapy delivered by collagen matrix [218]. The biodegradability of collagen and its low immunogenicity make it a substrate of choice for internal and topical pharmacogenomical applications.

5. Conclusion

Collagen-based biomaterials are of the utmost importance for tissue engineering and regenerative medicine. Because of its superior biocompatibility and low immunogenicity, collagen is still the protein of choice for biomaterials preparation. It can be extracted from various tissue sources and assembled in combination with other molecules. There is also a use in the laboratory as a decellularized ECM in fundamental studies or as tissue replacement material in medical applications. Most present research is aimed at the optimization of collagen-based biomaterials for medical applications by enhancing mechanical strength, biodegradability or delivery characteristics.

References and Notes

  1. Alberts, B.; Johnson, A.; Lewis, J.; Raff, M.; Roberts, K. Molecular Biology of The Cell; Garland Science: New York, NY, USA, 2002. [Google Scholar]
  2. van der Rest, M.; Garrone, R. Collagen family of proteins. FASEB J. 1991, 5, 2814–2823. [Google Scholar]
  3. Prockop, D.J.; Kivirikko, K.I. Collagens: Molecular biology, diseases, and potentials for therapy. Annu Rev Biochem 1995, 64, 403–434. [Google Scholar] [CrossRef] [PubMed]
  4. Crumpton, M. The molecular basis of antigenicity and immunogenicity. In Protein Antigens; Selan, M., Ed.; Academic Press: New York, NY, USA, 1974; pp. 1–78. [Google Scholar]
  5. Schmitt, F.O.; Levine, L.; Drake, M.P.; Rubin, A.L.; Pfahl, D.; Davison, P.F. The antigenicity of tropocollagen. Proc. Natl. Acad. Sci. USA 1964, 51, 493–497. [Google Scholar] [CrossRef] [PubMed]
  6. Davison, P.F.; Levine, L.; Drake, M.P.; Rubin, A.; Bump, S. The serologic specificity of tropocollagen telopeptides. J. Exp. Med. 1967, 126, 331–346. [Google Scholar] [CrossRef] [PubMed]
  7. Steffen, C.; Timpl, R.; Wolff, I. Immunogenicity and specificity of collagen. V. Demonstration of three different antigenic determinants on calf collagen. Immunology 1968, 15, 135–144. [Google Scholar] [PubMed]
  8. Michaeli, D.; Martin, G.R.; Kettman, J.; Benjamini, E.; Leung, D.Y.; Blatt, B.A. Localization of antigenic determinants in the polypeptide chains of collagen. Science 1969, 166, 1522–1524. [Google Scholar] [CrossRef] [PubMed]
  9. Furthmayr, H.; Beil, W.; Timpl, R. Different antigenic determinants in the polypeptide chains of human collagen. FEBS Lett. 1971, 12, 341–344. [Google Scholar] [CrossRef] [PubMed]
  10. Lindsley, H.; Mannik, M.; Bornstein, P. The distribution of antigenic determinants in rat skin collagen. J. Exp. Med. 1971, 133, 1309–1324. [Google Scholar] [CrossRef] [PubMed]
  11. Timpl, R.; Beil, W.; Furthmayr, H.; Meigel, W.; Pontz, B. Characterization of conformation independent antigenic determinants in the triple-helical part of calf and rat collagen. Immunology 1971, 21, 1017–1030. [Google Scholar] [PubMed]
  12. Furthmayr, H.; Timpl, R. Immunochemistry of collagens and procollagens. Int. Rev. Connect. Tissue Res. 1976, 7, 61–99. [Google Scholar] [PubMed]
  13. Weadock, K.S.; Miller, E.J.; Keuffel, E.L.; Dunn, M.G. Effect of physical crosslinking methods on collagen-fiber durability in proteolytic solutions. J. Biomed. Mater. Res. 1996, 32, 221–226. [Google Scholar] [CrossRef] [PubMed]
  14. Harriger, M.D.; Supp, A.P.; Warden, G.D.; Boyce, S.T. Glutaraldehyde crosslinking of collagen substrates inhibits degradation in skin substitutes grafted to athymic mice. J. Biomed. Mater. Res. 1997, 35, 137–145. [Google Scholar] [CrossRef] [PubMed]
  15. Charriere, G.; Bejot, M.; Schnitzler, L.; Ville, G.; Hartmann, D.J. Reactions to a bovine collagen implant. Clinical and immunologic study in 705 patients. J. Am. Acad. Dermatol. 1989, 21, 1203–1208. [Google Scholar] [CrossRef] [PubMed]
  16. Eaglstein, W.H.; Alvarez, O.M.; Auletta, M.; Leffel, D.; Rogers, G.S.; Zitelli, J.A.; Norris, J.E.; Thomas, I.; Irondo, M.; Fewkes, J.; Hardin-Young, J.; Duff, R.G.; Sabolinski, M.L. Acute excisional wounds treated with a tissue-engineered skin (Apligraf). Dermatol. Surg. 1999, 25, 195–201. [Google Scholar] [CrossRef] [PubMed]
  17. Badylak, S.F.; Gilbert, T.W. Immune response to biologic scaffold materials. Semin. Immunol. 2008, 20, 109–116. [Google Scholar] [CrossRef] [PubMed]
  18. Wood, A.; Ogawa, M.; Portier, R.J.; Schexnayder, M.; Shirley, M.; Losso, J.N. Biochemical properties of alligator (Alligator mississippiensis) bone collagen. Comp. Biochem. Physiol. B Biochem. Mol. Biol. 2008, 151, 246–249. [Google Scholar] [CrossRef] [PubMed]
  19. Johnson, K.A.; Rogers, G.J.; Roe, S.C.; Howlett, C.R.; Clayton, M.K.; Milthorpe, B.K.; Schindhelm, K. Nitrous acid pretreatment of tendon xenografts cross-linked with glutaraldehyde and sterilized with gamma irradiation. Biomaterials 1999, 20, 1003–1015. [Google Scholar] [CrossRef] [PubMed]
  20. Exposito, J.Y.; Cluzel, C.; Garrone, R.; Lethias, C. Evolution of collagens. Anat. Rec. 2002, 268, 302–316. [Google Scholar] [CrossRef] [PubMed]
  21. Exposito, J.Y.; Le Guellec, D.; Lu, Q.; Garrone, R. Short chain collagens in sponges are encoded by a family of closely related genes. J. Biol. Chem. 1991, 266, 21923–21928. [Google Scholar] [PubMed]
  22. Sugiura, H.; Yunoki, S.; Kondo, E.; Ikoma, T.; Tanaka, J.; Yasuda, K. In vivo biological responses and bioresorption of tilapia scale collagen as a potential biomaterial. J Biomater Sci Polym. Ed. 2009, 20, 1353–1368. [Google Scholar] [CrossRef] [PubMed]
  23. Song, E.; Yeon Kim, S.; Chun, T.; Byun, H.J.; Lee, Y.M. Collagen scaffolds derived from a marine source and their biocompatibility. Biomaterials 2006, 27, 2951–2961. [Google Scholar] [CrossRef] [PubMed]
  24. Lin, Y.K.; Liu, D.C. Comparison of physical-chemical properties of type I collagen from different species. Food Chem. 2006, 99, 244–251. [Google Scholar] [CrossRef]
  25. Yang, C.; Hillas, P.J.; Baez, J.A.; Nokelainen, M.; Balan, J.; Tang, J.; Spiro, R.; Polarek, J.W. The application of recombinant human collagen in tissue engineering. BioDrugs 2004, 18, 103–119. [Google Scholar] [CrossRef] [PubMed]
  26. Badylak, S.F. Xenogeneic extracellular matrix as a scaffold for tissue reconstruction. Transpl. Immunol. 2004, 12, 367–377. [Google Scholar] [CrossRef] [PubMed]
  27. Goo, H.C.; Hwang, Y.S.; Choi, Y.R.; Cho, H.N.; Suh, H. Development of collagenase-resistant collagen and its interaction with adult human dermal fibroblasts. Biomaterials 2003, 24, 5099–5113. [Google Scholar] [CrossRef] [PubMed]
  28. Yannas, I.V.; Burke, J.F.; Orgill, D.P.; Skrabut, E.M. Wound tissue can utilize a polymeric template to synthesize a functional extension of skin. Science 1982, 215, 174–176. [Google Scholar] [CrossRef] [PubMed]
  29. Postlethwaite, A.E.; Seyer, J.M.; Kang, A.H. Chemotactic attraction of human fibroblasts to type I, II, and III collagens and collagen-derived peptides. Proc. Natl. Acad. Sci. USA 1978, 75, 871–875. [Google Scholar] [CrossRef] [PubMed]
  30. Aimes, R.T.; Quigley, J.P. Matrix metalloproteinase-2 is an interstitial collagenase. Inhibitor-free enzyme catalyzes the cleavage of collagen fibrils and soluble native type I collagen generating the specific 3/4- and 1/4-length fragments. J. Biol. Chem. 1995, 270, 5872–5876. [Google Scholar] [CrossRef] [PubMed]
  31. Fields, G.B. A model for interstitial collagen catabolism by mammalian collagenases. J. Theor. Biol. 1991, 153, 585–602. [Google Scholar] [CrossRef] [PubMed]
  32. Freije, J.M.; Diez-Itza, I.; Balbin, M.; Sanchez, L.M.; Blasco, R.; Tolivia, J.; Lopez-Otin, C. Molecular cloning and expression of collagenase-3, a novel human matrix metalloproteinase produced by breast carcinomas. J. Biol. Chem. 1994, 269, 16766–16773. [Google Scholar] [PubMed]
  33. Knauper, V.; Lopez-Otin, C.; Smith, B.; Knight, G.; Murphy, G. Biochemical characterization of human collagenase-3. J. Biol. Chem. 1996, 271, 1544–1550. [Google Scholar] [CrossRef] [PubMed]
  34. Ohuchi, E.; Imai, K.; Fujii, Y.; Sato, H.; Seiki, M.; Okada, Y. Membrane type 1 matrix metalloproteinase digests interstitial collagens and other extracellular matrix macromolecules. J. Biol. Chem. 1997, 272, 2446–2451. [Google Scholar] [CrossRef] [PubMed]
  35. Yang, M.; Kurkinen, M. Cloning and characterization of a novel matrix metalloproteinase (MMP), CMMP, from chicken embryo fibroblasts. CMMP, Xenopus XMMP, and human MMP19 have a conserved unique cysteine in the catalytic domain. J. Biol. Chem. 1998, 273, 17893–17900. [Google Scholar] [CrossRef] [PubMed]
  36. Allan, J.A.; Hembry, R.M.; Angal, S.; Reynolds, J.J.; Murphy, G. Binding of latent and high Mr active forms of stromelysin to collagen is mediated by the C-terminal domain. J. Cell Sci. 1991, 99, 789–795. [Google Scholar] [PubMed]
  37. Allan, J.A.; Docherty, A.J.; Barker, P.J.; Huskisson, N.S.; Reynolds, J.J.; Murphy, G. Binding of gelatinases A and B to type-I collagen and other matrix components. Biochem. J. 1995, 309, 299–306. [Google Scholar] [PubMed]
  38. Murphy, G.; Allan, J.A.; Willenbrock, F.; Cockett, M.I.; O'Connell, J.P.; Docherty, A.J. The role of the C-terminal domain in collagenase and stromelysin specificity. J. Biol. Chem. 1992, 267, 9612–9618. [Google Scholar] [PubMed]
  39. Lauer-Fields, J.L.; Fields, G.B. Triple-helical peptide analysis of collagenolytic protease activity. Biol. Chem. 2002, 383, 1095–1105. [Google Scholar] [CrossRef] [PubMed]
  40. Ruoslahti, E.; Hayman, E.G.; Pierschbacher, M.D. Extracellular matrices and cell adhesion. Arteriosclerosis 1985, 5, 581–594. [Google Scholar] [CrossRef] [PubMed]
  41. Smethurst, P.A.; Onley, D.J.; Jarvis, G.E.; O'Connor, M.N.; Knight, C.G.; Herr, A.B.; Ouwehand, W.H.; Farndale, R.W. Structural basis for the platelet-collagen interaction: The smallest motif within collagen that recognizes and activates platelet Glycoprotein VI contains two glycine-proline-hydroxyproline triplets. J. Biol. Chem. 2007, 282, 1296–1304. [Google Scholar] [CrossRef] [PubMed]
  42. Knight, C.G.; Morton, L.F.; Onley, D.J.; Peachey, A.R.; Messent, A.J.; Smethurst, P.A.; Tuckwell, D.S.; Farndale, R.W.; Barnes, M.J. Identification in collagen type I of an integrin alpha2 beta1-binding site containing an essential GER sequence. J. Biol. Chem. 1998, 273, 33287–33294. [Google Scholar] [CrossRef] [PubMed]
  43. Knight, C.G.; Morton, L.F.; Peachey, A.R.; Tuckwell, D.S.; Farndale, R.W.; Barnes, M.J. The collagen-binding A-domains of integrins alpha(1)beta(1) and alpha(2)beta(1) recognize the same specific amino acid sequence, GFOGER, in native (triple-helical) collagens. J. Biol. Chem. 2000, 275, 35–40. [Google Scholar] [CrossRef] [PubMed]
  44. Konitsiotis, A.D.; Raynal, N.; Bihan, D.; Hohenester, E.; Farndale, R.W.; Leitinger, B. Characterization of high affinity binding motifs for the discoidin domain receptor DDR2 in collagen. J. Biol. Chem. 2008, 283, 6861–6868. [Google Scholar] [CrossRef] [PubMed]
  45. Gullberg, D.; Gehlsen, K.R.; Turner, D.C.; Ahlen, K.; Zijenah, L.S.; Barnes, M.J.; Rubin, K. Analysis of alpha 1 beta 1, alpha 2 beta 1 and alpha 3 beta 1 integrins in cell--collagen interactions: Identification of conformation dependent alpha 1 beta 1 binding sites in collagen type I. EMBO J. 1992, 11, 3865–3873. [Google Scholar] [PubMed]
  46. Ruoslahti, E.; Vaheri, A. Novel human serum protein from fibroblast plasma membrane. Nature 1974, 248, 789–791. [Google Scholar] [CrossRef] [PubMed]
  47. Pierschbacher, M.D.; Ruoslahti, E. Cell attachment activity of fibronectin can be duplicated by small synthetic fragments of the molecule. Nature 1984, 309, 30–33. [Google Scholar] [CrossRef] [PubMed]
  48. Fiedler, L.R.; Schonherr, E.; Waddington, R.; Niland, S.; Seidler, D.G.; Aeschlimann, D.; Eble, J.A. Decorin regulates endothelial cell motility on collagen I through activation of insulin-like growth factor I receptor and modulation of alpha2beta1 integrin activity. J. Biol. Chem. 2008, 283, 17406–17415. [Google Scholar] [CrossRef] [PubMed]
  49. Gilbert, T.W.; Sellaro, T.L.; Badylak, S.F. Decellularization of tissues and organs. Biomaterials 2006, 27, 3675–3683. [Google Scholar] [PubMed]
  50. Boyce, S.T.; Christianson, D.J.; Hansbrough, J.F. Structure of a collagen-GAG dermal skin substitute optimized for cultured human epidermal keratinocytes. J. Biomed. Mater. Res. 1988, 22, 939–957. [Google Scholar] [CrossRef] [PubMed]
  51. Ellis, D.L.; Yannas, I.V. Recent advances in tissue synthesis in vivo by use of collagen-glycosaminoglycan copolymers. Biomaterials 1996, 17, 291–299. [Google Scholar] [CrossRef] [PubMed]
  52. Chen, P.; Marsilio, E.; Goldstein, R.H.; Yannas, I.V.; Spector, M. Formation of lung alveolar-like structures in collagen-glycosaminoglycan scaffolds in vitro. Tissue Eng. 2005, 11, 1436–1448. [Google Scholar] [CrossRef] [PubMed]
  53. Aprahamian, M.; Lambert, A.; Balboni, G.; Lefebvre, F.; Schmitthaeusler, R.; Damge, C.; Rabaud, M. A new reconstituted connective tissue matrix: Preparation, biochemical, structural and mechanical studies. J. Biomed. Mater. Res. 1987, 21, 965–977. [Google Scholar] [CrossRef] [PubMed]
  54. Buijtenhuijs, P.; Buttafoco, L.; Poot, A.A.; Daamen, W.F.; van Kuppevelt, T.H.; Dijkstra, P.J.; de Vos, R.A.; Sterk, L.M.; Geelkerken, B.R.; Feijen, J.; Vermes, I. Tissue engineering of blood vessels: Characterization of smooth-muscle cells for culturing on collagen-and-elastin-based scaffolds. Biotechnol. Appl. Biochem. 2004, 39, 141–149. [Google Scholar] [CrossRef] [PubMed]
  55. Garcia, Y.; Hemantkumar, N.; Collighan, R.; Griffin, M.; Rodriguez-Cabello, J.C.; Pandit, A. In vitro characterization of a collagen scaffold enzymatically cross-linked with a tailored elastin-like polymer. Tissue Eng. A 2009, 15, 887–899. [Google Scholar] [CrossRef]
  56. Damour, O.; Gueugniaud, P.Y.; Berthin-Maghit, M.; Rousselle, P.; Berthod, F.; Sahuc, F.; Collombel, C. A dermal substrate made of collagen--GAG--chitosan for deep burn coverage: First clinical uses. Clin. Mater. 1994, 15, 273–276. [Google Scholar] [CrossRef] [PubMed]
  57. Shahabeddin, L.; Berthod, F.; Damour, O.; Collombel, C. Characterization of skin reconstructed on a chitosan-cross-linked collagen-glycosaminoglycan matrix. Skin Pharmacol. 1990, 3, 107–114. [Google Scholar] [CrossRef] [PubMed]
  58. Wu, X.; Black, L.; Santacana-Laffitte, G.; Patrick, C.W., Jr. Preparation and assessment of glutaraldehyde-crosslinked collagen-chitosan hydrogels for adipose tissue engineering. J. Biomed. Mater. Res. A 2007, 81, 59–65. [Google Scholar] [CrossRef] [PubMed]
  59. Steven, F.S.; Tristram, G.R. The presence of non-protein nitrogen in acetic acid-soluble calf-skin collagen. Biochem. J. 1962, 83, 240–244. [Google Scholar] [PubMed]
  60. Steven, F.S.; Jackson, D.S. Purification and amino acid composition of monomeric and polymeric collagens. Biochem. J. 1967, 104, 534–536. [Google Scholar] [PubMed]
  61. Eastoe, J.E. The amino acid composition of mammalian collagen and gelatin. Biochem. J. 1955, 61, 589–600. [Google Scholar] [PubMed]
  62. Gross, J.; Highberger, J.H.; Schmitt, F.O. Extraction of collagen from connective tissue by neutral salt solutions. Proc. Natl. Acad. Sci. USA 1955, 41, 1–7. [Google Scholar] [CrossRef] [PubMed]
  63. Grant, N.H.; Alburn, H.E. Collagen solubilization by mammalian proteinases. Arch. Biochem. Biophys. 1960, 89, 262–270. [Google Scholar] [CrossRef] [PubMed]
  64. Steven, F.S. The nishihara technique for the solubilization of collagen. Application to the preparation of soluble collagens from normal and rheumatoid connective tissue. Ann. Rheum. Dis. 1964, 23, 300–301. [Google Scholar] [CrossRef] [PubMed]
  65. Drake, M.P.; Davison, P.F.; Bump, S.; Schmitt, F.O. Action of proteolytic enzymes on tropocollagen and insoluble collagen. Biochemistry 1966, 5, 301–312. [Google Scholar] [CrossRef] [PubMed]
  66. Rubin, A.L.; Pfahl, D.; Speakman, P.T.; Davison, P.F.; Schmitt, F.O. Tropocollagen: Significance of protease-induced alterations. Science 1963, 139, 37–39. [Google Scholar] [CrossRef] [PubMed]
  67. Miller, E.J.; Rhodes, R.K. Preparation and characterization of the different types of collagen. Methods Enzymol. 1982, 82, 33–64. [Google Scholar] [PubMed]
  68. Miller, E.J. Structural studies on cartilage collagen employing limited cleavage and solubilization with pepsin. Biochemistry 1972, 11, 4903–4909. [Google Scholar] [CrossRef] [PubMed]
  69. Weadock, K.S.; Miller, E.J.; Bellincampi, L.D.; Zawadsky, J.P.; Dunn, M.G. Physical crosslinking of collagen fibers: Comparison of ultraviolet irradiation and dehydrothermal treatment. J. Biomed. Mater. Res. 1995, 29, 1373–1379. [Google Scholar] [CrossRef] [PubMed]
  70. Ohan, M.P.; Weadock, K.S.; Dunn, M.G. Synergistic effects of glucose and ultraviolet irradiation on the physical properties of collagen. J. Biomed. Mater. Res. 2002, 60, 384–391. [Google Scholar] [CrossRef] [PubMed]
  71. Chvapil, M.; Owen, J.A.; Clark, D.S. Effect of collagen crosslinking on the rate of resorption of implanted collagen tubing in rabbits. J. Biomed. Mater. Res. 1977, 11, 297–314. [Google Scholar] [CrossRef] [PubMed]
  72. Yannas, I.V.; Burke, J.F. Design of an artificial skin. I. Basic design principles. J. Biomed. Mater. Res. 1980, 14, 65–81. [Google Scholar] [CrossRef] [PubMed]
  73. Osborne, C.S.; Barbenel, J.C.; Smith, D.; Savakis, M.; Grant, M.H. Investigation into the tensile properties of collagen/chondroitin-6-sulphate gels: The effect of crosslinking agents and diamines. Med. Biol. Eng. Comput. 1998, 36, 129–134. [Google Scholar] [CrossRef] [PubMed]
  74. Powell, H.M.; Boyce, S.T. EDC cross-linking improves skin substitute strength and stability. Biomaterials 2006, 27, 5821–5827. [Google Scholar] [CrossRef] [PubMed]
  75. Powell, H.M.; Boyce, S.T. Wound closure with EDC cross-linked cultured skin substitutes grafted to athymic mice. Biomaterials 2007, 28, 1084–1092. [Google Scholar] [CrossRef] [PubMed]
  76. Duan, X.; Sheardown, H. Crosslinking of collagen with dendrimers. J. Biomed. Mater. Res.A 2005, 75, 510–518. [Google Scholar] [CrossRef] [PubMed]
  77. Castaneda, L.; Valle, J.; Yang, N.; Pluskat, S.; Slowinska, K. Collagen cross-linking with Au nanoparticles. Biomacromolecules 2008, 9, 3383–3388. [Google Scholar] [CrossRef] [PubMed]
  78. Zeeman, R.; Dijkstra, P.J.; van Wachem, P.B.; van Luyn, M.J.; Hendriks, M.; Cahalan, P.T.; Feijen, J. Successive epoxy and carbodiimide cross-linking of dermal sheep collagen. Biomaterials 1999, 20, 921–931. [Google Scholar] [CrossRef] [PubMed]
  79. Everaerts, F.; Torrianni, M.; Hendriks, M.; Feijen, J. Biomechanical properties of carbodiimide crosslinked collagen: Influence of the formation of ester crosslinks. J. Biomed. Mater. Res. A 2008, 85, 547–555. [Google Scholar] [CrossRef] [PubMed]
  80. van Wachem, P.B.; van Luyn, M.J.; Olde Damink, L.H.; Dijkstra, P.J.; Feijen, J.; Nieuwenhuis, P. Biocompatibility and tissue regenerating capacity of crosslinked dermal sheep collagen. J. Biomed. Mater. Res. 1994, 28, 353–363. [Google Scholar] [CrossRef] [PubMed]
  81. Zeugolis, D.I.; Paul, G.R.; Attenburrow, G. Cross-linking of extruded collagen fibers-a biomimetic three-dimensional scaffold for tissue engineering applications. J. Biomed. Mater. Res. A 2009, 89, 895–908. [Google Scholar] [CrossRef] [PubMed]
  82. Sung, H.W.; Huang, R.N.; Huang, L.L.; Tsai, C.C. In vitro evaluation of cytotoxicity of a naturally occurring cross-linking reagent for biological tissue fixation. J. Biomater. Sci. Polym. Ed. 1999, 10, 63–78. [Google Scholar] [CrossRef] [PubMed]
  83. Sundararaghavan, H.G.; Monteiro, G.A.; Lapin, N.A.; Chabal, Y.J.; Miksan, J.R.; Shreiber, D.I. Genipin-induced changes in collagen gels: Correlation of mechanical properties to fluorescence. J. Biomed. Mater. Res.A 2008, 87, 308–320. [Google Scholar] [CrossRef] [PubMed]
  84. Speer, D.P.; Chvapil, M.; Eskelson, C.D.; Ulreich, J. Biological effects of residual glutaraldehyde in glutaraldehyde-tanned collagen biomaterials. J. Biomed. Mater. Res. 1980, 14, 753–764. [Google Scholar] [CrossRef] [PubMed]
  85. van Luyn, M.J.; van Wachem, P.B.; Olde Damink, L.H.; Dijkstra, P.J.; Feijen, J.; Nieuwenhuis, P. Secondary cytotoxicity of cross-linked dermal sheep collagens during repeated exposure to human fibroblasts. Biomaterials 1992, 13, 1017–1024. [Google Scholar] [CrossRef] [PubMed]
  86. Berthod, F.; Saintigny, G.; Chretien, F.; Hayek, D.; Collombel, C.; Damour, O. Optimization of thickness, pore size and mechanical properties of a biomaterial designed for deep burn coverage. Clin. Mater. 1994, 15, 259–265. [Google Scholar] [CrossRef] [PubMed]
  87. Berthod, F.; Hayek, D.; Damour, O.; Collombel, C. Collagen synthesis by fibroblasts cultured within a collagen sponge. Biomaterials 1993, 14, 749–754. [Google Scholar] [CrossRef] [PubMed]
  88. Yung, C.W.; Wu, L.Q.; Tullman, J.A.; Payne, G.F.; Bentley, W.E.; Barbari, T.A. Transglutaminase crosslinked gelatin as a tissue engineering scaffold. J. Biomed. Mater. Res. A 2007, 83, 1039–1046. [Google Scholar] [CrossRef] [PubMed]
  89. Khew, S.T.; Yang, Q.J.; Tong, Y.W. Enzymatically crosslinked collagen-mimetic dendrimers that promote integrin-targeted cell adhesion. Biomaterials 2008, 29, 3034–3045. [Google Scholar] [CrossRef] [PubMed]
  90. Yeo, T.K.; Brown, L.; Dvorak, H.F. Alterations in proteoglycan synthesis common to healing wounds and tumors. Am. J. Pathol. 1991, 138, 1437–1450. [Google Scholar] [PubMed]
  91. Teti, A. Regulation of cellular functions by extracellular matrix. J. Am. Soc. Nephrol. 1992, 2, 83–87. [Google Scholar]
  92. Huang-Lee, L.L.; Wu, J.H.; Nimni, M.E. Effects of hyaluronan on collagen fibrillar matrix contraction by fibroblasts. J. Biomed. Mater. Res. 1994, 28, 123–132. [Google Scholar] [CrossRef] [PubMed]
  93. Zhong, S.; Yung, L.Y. Enhanced biological stability of collagen with incorporation of PAMAM dendrimer. J. Biomed. Mater. Res. A 2009, 91, 114–122. [Google Scholar] [CrossRef] [PubMed]
  94. Caissie, R.; Gingras, M.; Champigny, M.F.; Berthod, F. In vivo enhancement of sensory perception recovery in a tissue-engineered skin enriched with laminin. Biomaterials 2006, 27, 2988–2993. [Google Scholar] [CrossRef] [PubMed]
  95. Antonicelli, F.; Bellon, G.; Lorimier, S.; Hornebeck, W. Role of the elastin receptor complex (S-Gal/Cath-A/Neu-1) in skin repair and regeneration. Wound Repair Regen. 2009, 17, 631–638. [Google Scholar] [CrossRef] [PubMed]
  96. Suh, H.; Lee, J.E. Behavior of fibroblasts on a porous hyaluronic acid incorporated collagen matrix. Yonsei Med. J. 2002, 43, 193–202. [Google Scholar] [CrossRef] [PubMed]
  97. Roe, S.C.; Milthorpe, B.K.; True, K.; Rogers, G.J.; Schindhelm, K. The effect of gamma irradiation on a xenograft tendon bioprosthesis. Clin. Mater. 1992, 9, 149–154. [Google Scholar] [CrossRef] [PubMed]
  98. Cheung, D.T.; Perelman, N.; Tong, D.; Nimni, M.E. The effect of gamma-irradiation on collagen molecules, isolated alpha-chains, and crosslinked native fibers. J. Biomed. Mater. Res. 1990, 24, 581–589. [Google Scholar] [CrossRef] [PubMed]
  99. Mollers, S.; Heschel, I.; Damink, L.H.; Schugner, F.; Deumens, R.; Muller, B.; Bozkurt, A.; Nava, J.G.; Noth, J.; Brook, G.A. Cytocompatibility of a novel, longitudinally microstructured collagen scaffold intended for nerve tissue repair. Tissue Eng. A 2009, 15, 461–472. [Google Scholar] [CrossRef]
  100. Ohan, M.P.; Dunn, M.G. Glucose stabilizes collagen sterilized with gamma irradiation. J. Biomed. Mater. Res. A 2003, 67, 1188–1195. [Google Scholar] [CrossRef] [PubMed]
  101. Noah, E.M.; Chen, J.; Jiao, X.; Heschel, I.; Pallua, N. Impact of sterilization on the porous design and cell behavior in collagen sponges prepared for tissue engineering. Biomaterials 2002, 23, 2855–2861. [Google Scholar] [CrossRef] [PubMed]
  102. Friess, W.; Schlapp, M. Sterilization of gentamicin containing collagen/PLGA microparticle composites. Eur. J. Pharm. Biopharm. 2006, 63, 176–187. [Google Scholar] [CrossRef] [PubMed]
  103. Grimes, M.; Pembroke, J.T.; McGloughlin, T. The effect of choice of sterilisation method on the biocompatibility and biodegradability of SIS (small intestinal submucosa). Biomed. Mater. Eng. 2005, 15, 65–71. [Google Scholar] [PubMed]
  104. Wilshaw, S.P.; Kearney, J.N.; Fisher, J.; Ingham, E. Production of an acellular amniotic membrane matrix for use in tissue engineering. Tissue Eng. 2006, 12, 2117–2129. [Google Scholar] [CrossRef] [PubMed]
  105. Doillon, C.J.; Drouin, R.; Cote, M.F.; Dallaire, N.; Pageau, J.F.; Laroche, G. Chemical inactivators as sterilization agents for bovine collagen materials. J. Biomed. Mater. Res. 1997, 37, 212–221. [Google Scholar] [CrossRef] [PubMed]
  106. Ma, L.; Gao, C.; Mao, Z.; Zhou, J.; Shen, J.; Hu, X.; Han, C. Collagen/chitosan porous scaffolds with improved biostability for skin tissue engineering. Biomaterials 2003, 24, 4833–4841. [Google Scholar] [CrossRef] [PubMed]
  107. Gingras, M.; Paradis, I.; Berthod, F. Nerve regeneration in a collagen-chitosan tissue-engineered skin transplanted on nude mice. Biomaterials 2003, 24, 1653–1661. [Google Scholar] [CrossRef] [PubMed]
  108. Wiegand, C.; Abel, M.; Ruth, P.; Wilhelms, T.; Schulze, D.; Norgauer, J.; Hipler, U.C. Effect of the sterilization method on the performance of collagen type I on chronic wound parameters in vitro. J. Biomed. Mater. Res. B Appl. Biomater. 2009, 90, 710–719. [Google Scholar] [CrossRef] [PubMed]
  109. Xu, T.; Molnar, P.; Gregory, C.; Das, M.; Boland, T.; Hickman, J.J. Electrophysiological characterization of embryonic hippocampal neurons cultured in a 3D collagen hydrogel. Biomaterials 2009, 30, 4377–4383. [Google Scholar] [CrossRef] [PubMed]
  110. Ma, W.; Fitzgerald, W.; Liu, Q.Y.; O'Shaughnessy, T.J.; Maric, D.; Lin, H.J.; Alkon, D.L.; Barker, J.L. CNS stem and progenitor cell differentiation into functional neuronal circuits in three-dimensional collagen gels. Exp. Neurol. 2004, 190, 276–288. [Google Scholar] [CrossRef] [PubMed]
  111. O'Shaughnessy, T.J.; Lin, H.J.; Ma, W. Functional synapse formation among rat cortical neurons grown on three-dimensional collagen gels. Neurosci. Lett. 2003, 340, 169–172. [Google Scholar] [CrossRef] [PubMed]
  112. Gingras, M.; Beaulieu, M.M.; Gagnon, V.; Durham, H.D.; Berthod, F. In vitro study of axonal migration and myelination of motor neurons in a three-dimensional tissue-engineered model. Glia 2008, 56, 354–364. [Google Scholar] [CrossRef] [PubMed]
  113. Che, Z.M.; Jung, T.H.; Choi, J.H.; Yoon do, J.; Jeong, H.J.; Lee, E.J.; Kim, J. Collagen-based co-culture for invasive study on cancer cells-fibroblasts interaction. Biochem. Biophys. Res. Commun. 2006, 346, 268–275. [Google Scholar] [CrossRef] [PubMed]
  114. Sabeh, F.; Shimizu-Hirota, R.; Weiss, S.J. Protease-dependent versus -independent cancer cell invasion programs: Three-dimensional amoeboid movement revisited. J. Cell Biol. 2009, 185, 11–19. [Google Scholar] [CrossRef] [PubMed]
  115. Inoue, T.; Toda, S.; Narisawa, Y.; Sugihara, H. Subcutaneous adipocytes promote the differentiation of squamous cell carcinoma cell line (DJM-1) in collagen gel matrix culture. J. Invest. Dermatol. 2001, 117, 244–250. [Google Scholar] [CrossRef] [PubMed]
  116. Shanmugasundaram, N.; Ravichandran, P.; Reddy, P.N.; Ramamurty, N.; Pal, S.; Rao, K.P. Collagen-chitosan polymeric scaffolds for the in vitro culture of human epidermoid carcinoma cells. Biomaterials 2001, 22, 1943–1951. [Google Scholar] [CrossRef] [PubMed]
  117. Stachowiak, A.N.; Irvine, D.J. Inverse opal hydrogel-collagen composite scaffolds as a supportive microenvironment for immune cell migration. J. Biomed. Mater. Res. A 2008, 85, 815–828. [Google Scholar] [CrossRef] [PubMed]
  118. Wolf, K.; Muller, R.; Borgmann, S.; Brocker, E.B.; Friedl, P. Amoeboid shape change and contact guidance: T-lymphocyte crawling through fibrillar collagen is independent of matrix remodeling by MMPs and other proteases. Blood 2003, 102, 3262–3269. [Google Scholar] [CrossRef] [PubMed]
  119. Spencer, N.J.; Cotanche, D.A.; Klapperich, C.M. Peptide- and collagen-based hydrogel substrates for in vitro culture of chick cochleae. Biomaterials 2008, 29, 1028–1042. [Google Scholar] [CrossRef] [PubMed]
  120. Cortial, D.; Gouttenoire, J.; Rousseau, C.F.; Ronziere, M.C.; Piccardi, N.; Msika, P.; Herbage, D.; Mallein-Gerin, F.; Freyria, A.M. Activation by IL-1 of bovine articular chondrocytes in culture within a 3D collagen-based scaffold. An in vitro model to address the effect of compounds with therapeutic potential in osteoarthritis. Osteoarthritis Cartilage 2006, 14, 631–640. [Google Scholar] [CrossRef] [PubMed]
  121. Harley, B.A.; Lynn, A.K.; Wissner-Gross, Z.; Bonfield, W.; Yannas, I.V.; Gibson, L.J. Design of a multiphase osteochondral scaffold. II. Fabrication of a mineralized collagen-glycosaminoglycan scaffold. J. Biomed. Mater. Res. A 2010, 92, 1066–1077. [Google Scholar] [PubMed]
  122. Du, C.; Cui, F.Z.; Zhang, W.; Feng, Q.L.; Zhu, X.D.; de Groot, K. Formation of calcium phosphate/collagen composites through mineralization of collagen matrix. J. Biomed. Mater. Res. 2000, 50, 518–527. [Google Scholar] [CrossRef] [PubMed]
  123. Ciardelli, G.; Gentile, P.; Chiono, V.; Mattioli-Belmonte, M.; Vozzi, G.; Barbani, N.; Giusti, P. Enzymatically crosslinked porous composite matrices for bone tissue regeneration. J. Biomed. Mater. Res. A 2009, 92, 137–151. [Google Scholar]
  124. Dubey, D.K.; Tomar, V. Role of the nanoscale interfacial arrangement in mechanical strength of tropocollagen-hydroxyapatite-based hard biomaterials. Acta Biomater. 2009, 5, 2704–2716. [Google Scholar] [CrossRef] [PubMed]
  125. Liao, S.; Ngiam, M.; Chan, C.K.; Ramakrishna, S. Fabrication of nano-hydroxyapatite/collagen/osteonectin composites for bone graft applications. Biomed. Mater. 2009, 4, 25019. [Google Scholar] [CrossRef]
  126. Tamimi, F.; Kumarasami, B.; Doillon, C.; Gbureck, U.; Le Nihouannen, D.; Cabarcos, E.L.; Barralet, J.E. Brushite-collagen composites for bone regeneration. Acta Biomater. 2008, 4, 1315–1321. [Google Scholar] [CrossRef] [PubMed]
  127. Jayaraman, M.; Subramanian, M.V. Preparation and characterization of two new composites: Collagen-brushite and collagen octa-calcium phosphate. Med. Sci. Monit. 2002, 8, BR481–487. [Google Scholar] [PubMed]
  128. Tebb, T.A.; Tsai, S.W.; Glattauer, V.; White, J.F.; Ramshaw, J.A.; Werkmeister, J.A. Development of porous collagen beads for chondrocyte culture. Cytotechnology 2006, 52, 99–106. [Google Scholar] [CrossRef] [PubMed]
  129. Glattauer, V.; White, J.F.; Tsai, W.B.; Tsai, C.C.; Tebb, T.A.; Danon, S.J.; Werkmeister, J.A.; Ramshaw, J.A. Preparation of resorbable collagen-based beads for direct use in tissue engineering and cell therapy applications. J. Biomed. Mater. Res. A 2010, 92, 1301–1309. [Google Scholar] [PubMed]
  130. Gastel, J.A.; Muirhead, W.R.; Lifrak, J.T.; Fadale, P.D.; Hulstyn, M.J.; Labrador, D.P. Meniscal tissue regeneration using a collagenous biomaterial derived from porcine small intestine submucosa. Arthroscopy 2001, 17, 151–159. [Google Scholar] [CrossRef] [PubMed]
  131. Cook, J.L.; Fox, D.B.; Malaviya, P.; Tomlinson, J.L.; Farr, J.; Kuroki, K.; Cook, C.R. Evaluation of small intestinal submucosa grafts for meniscal regeneration in a clinically relevant posterior meniscectomy model in dogs. J. Knee Surg. 2006, 19, 159–167. [Google Scholar] [PubMed]
  132. De Franceschi, L.; Grigolo, B.; Roseti, L.; Facchini, A.; Fini, M.; Giavaresi, G.; Tschon, M.; Giardino, R. Transplantation of chondrocytes seeded on collagen-based scaffold in cartilage defects in rabbits. J. Biomed. Mater. Res. A 2005, 75, 612–622. [Google Scholar] [CrossRef] [PubMed]
  133. Freyria, A.M.; Ronziere, M.C.; Cortial, D.; Galois, L.; Hartmann, D.; Herbage, D.; Mallein-Gerin, F. Comparative phenotypic analysis of articular chondrocytes cultured within type I or type II collagen scaffolds. Tissue Eng. A 2009, 15, 1233–1245. [Google Scholar] [CrossRef]
  134. Schneider, R.K.; Puellen, A.; Kramann, R.; Raupach, K.; Bornemann, J.; Knuechel, R.; Perez-Bouza, A.; Neuss, S. The osteogenic differentiation of adult bone marrow and perinatal umbilical mesenchymal stem cells and matrix remodelling in three-dimensional collagen scaffolds. Biomaterials 2010, 31, 467–480. [Google Scholar] [CrossRef] [PubMed]
  135. Murphy, C.M.; Haugh, M.G.; O'Brien, F.J. The effect of mean pore size on cell attachment, proliferation and migration in collagen-glycosaminoglycan scaffolds for bone tissue engineering. Biomaterials 2010, 31, 461–466. [Google Scholar] [CrossRef] [PubMed]
  136. Yamasaki, T.; Deie, M.; Shinomiya, R.; Yasunaga, Y.; Yanada, S.; Ochi, M. Transplantation of meniscus regenerated by tissue engineering with a scaffold derived from a rat meniscus and mesenchymal stromal cells derived from rat bone marrow. Artif. Organs 2008, 32, 519–524. [Google Scholar] [CrossRef] [PubMed]
  137. Stapleton, T.W.; Ingram, J.; Katta, J.; Knight, R.; Korossis, S.; Fisher, J.; Ingham, E. Development and characterization of an acellular porcine medial meniscus for use in tissue engineering. Tissue Eng. A 2008, 14, 505–518. [Google Scholar] [CrossRef]
  138. Tedder, M.E.; Liao, J.; Weed, B.; Stabler, C.; Zhang, H.; Simionescu, A.; Simionescu, D.T. Stabilized collagen scaffolds for heart valve tissue engineering. Tissue Eng. A 2009, 15, 1257–1268. [Google Scholar] [CrossRef]
  139. Eitan, Y.; Sarig, U.; Dahan, N.; Machluf, M. Acellular cardiac extracellular matrix as a scaffold for tissue engineering: In-vitro cell support, remodeling and biocompatibility. Tissue Eng. C Methods 2010, in press. [Google Scholar]
  140. Somers, P.; Cuvelier, C.A.; Somer, F.D.; Cornelissen, M.; Cox, E.; Verloo, M.; Chiers, K.; van Nooten, G. Gamma radiation alters the ultrastructure in tissue-engineered heart valve scaffolds. Tissue Eng. A 2009, 15, 3597–3604. [Google Scholar] [CrossRef]
  141. Konuma, T.; Devaney, E.J.; Bove, E.L.; Gelehrter, S.; Hirsch, J.C.; Tavakkol, Z.; Ohye, R.G. Performance of CryoValve SG decellularized pulmonary allografts compared with standard cryopreserved allografts. Ann. Thorac. Surg. 2009, 88, 849–854; discussion 554–845. [Google Scholar] [CrossRef] [PubMed]
  142. O'Brien, M.F.; Goldstein, S.; Walsh, S.; Black, K.S.; Elkins, R.; Clarke, D. The SynerGraft valve: A new acellular (nonglutaraldehyde-fixed) tissue heart valve for autologous recellularization first experimental studies before clinical implantation. Semin. Thorac. Cardiovasc. Surg. 1999, 11, 194–200. [Google Scholar] [CrossRef] [PubMed]
  143. Bechtel, J.F.; Muller-Steinhardt, M.; Schmidtke, C.; Brunswik, A.; Stierle, U.; Sievers, H.H. Evaluation of the decellularized pulmonary valve homograft (SynerGraft). J. Heart Valve Dis. 2003, 12, 734–739; discussion 739–740. [Google Scholar] [PubMed]
  144. Ott, H.C.; Matthiesen, T.S.; Goh, S.K.; Black, L.D.; Kren, S.M.; Netoff, T.I.; Taylor, D.A. Perfusion-decellularized matrix: Using nature's platform to engineer a bioartificial heart. Nat. Med. 2008, 14, 213–221. [Google Scholar] [CrossRef] [PubMed]
  145. Teebken, O.E.; Puschmann, C.; Breitenbach, I.; Rohde, B.; Burgwitz, K.; Haverich, A. Preclinical development of tissue-engineered vein valves and venous substitutes using re-endothelialised human vein matrix. Eur. J. Vasc. Endovasc. Surg. 2009, 37, 92–102. [Google Scholar] [CrossRef] [PubMed]
  146. L'Heureux, N.; Paquet, S.; Labbe, R.; Germain, L.; Auger, F.A. A completely biological tissue-engineered human blood vessel. FASEB J. 1998, 12, 47–56. [Google Scholar] [PubMed]
  147. L'Heureux, N.; Stoclet, J.C.; Auger, F.A.; Lagaud, G.J.; Germain, L.; Andriantsitohaina, R. A human tissue-engineered vascular media: A new model for pharmacological studies of contractile responses. FASEB J. 2001, 15, 515–524. [Google Scholar] [CrossRef] [PubMed]
  148. Laflamme, K.; Roberge, C.J.; Labonte, J.; Pouliot, S.; D'Orleans-Juste, P.; Auger, F.A.; Germain, L. Tissue-engineered human vascular media with a functional endothelin system. Circulation 2005, 111, 459–464. [Google Scholar] [CrossRef] [PubMed]
  149. McAllister, T.N.; Maruszewski, M.; Garrido, S.A.; Wystrychowski, W.; Dusserre, N.; Marini, A.; Zagalski, K.; Fiorillo, A.; Avila, H.; Manglano, X.; Antonelli, J.; Kocher, A.; Zembala, M.; Cierpka, L.; de la Fuente, L.M.; L'Heureux, N. Effectiveness of haemodialysis access with an autologous tissue-engineered vascular graft: A multicentre cohort study. Lancet 2009, 373, 1440–1446. [Google Scholar] [CrossRef] [PubMed]
  150. L'Heureux, N.; McAllister, T.N.; de la Fuente, L.M. Tissue-engineered blood vessel for adult arterial revascularization. N. Engl. J. Med. 2007, 357, 1451–1453. [Google Scholar] [CrossRef] [PubMed]
  151. Doillon, C.J.; Silver, F.H. Collagen-based wound dressing: Effects of hyaluronic acid and fibronectin on wound healing. Biomaterials 1986, 7, 3–8. [Google Scholar] [CrossRef] [PubMed]
  152. Peters, W.J. Biological dressings in burns-A review. Ann. Plastic. Surg. 1980, 4, 133–137. [Google Scholar] [CrossRef]
  153. Regnier, M.; Staquet, M.J.; Schmitt, D.; Schmidt, R. Integration of Langerhans cells into a pigmented reconstructed human epidermis. J. Invest. Dermatol. 1997, 109, 510–512. [Google Scholar] [CrossRef] [PubMed]
  154. Tremblay, P.L.; Hudon, V.; Berthod, F.; Germain, L.; Auger, F.A. Inosculation of tissue-engineered capillaries with the host's vasculature in a reconstructed skin transplanted on mice. Am. J. Transplant. 2005, 5, 1002–1010. [Google Scholar] [CrossRef] [PubMed]
  155. Bechetoille, N.; Dezutter-Dambuyant, C.; Damour, O.; Andre, V.; Orly, I.; Perrier, E. Effects of solar ultraviolet radiation on engineered human skin equivalent containing both Langerhans cells and dermal dendritic cells. Tissue Eng. 2007, 13, 2667–2679. [Google Scholar] [CrossRef] [PubMed]
  156. Blais, M.; Grenier, M.; Berthod, F. Improvement of nerve regeneration in tissue-engineered skin enriched with schwann cells. J. Invest. Dermatol. 2009, 129, 2895–2900. [Google Scholar] [CrossRef] [PubMed]
  157. Trottier, V.; Marceau-Fortier, G.; Germain, L.; Vincent, C.; Fradette, J. IFATS collection: Using human adipose-derived stem/stromal cells for the production of new skin substitutes. Stem Cells 2008, 26, 2713–2723. [Google Scholar] [CrossRef] [PubMed]
  158. Jean, J.; Lapointe, M.; Soucy, J.; Pouliot, R. Development of an in vitro psoriatic skin model by tissue engineering. J. Dermatol. Sci. 2009, 53, 19–25. [Google Scholar] [CrossRef] [PubMed]
  159. Corriveau, M.P.; Boufaied, I.; Lessard, J.; Chabaud, S.; Senecal, J.L.; Grodzicky, T.; Chartier, S.; Raymond, Y.; Moulin, V.J. The fibrotic phenotype of systemic sclerosis fibroblasts varies with disease duration and severity of skin involvement: Reconstitution of skin fibrosis development using a tissue engineering approach. J. Pathol. 2009, 217, 534–542. [Google Scholar] [CrossRef] [PubMed]
  160. Edmonds, M. Apligraf in the treatment of neuropathic diabetic foot ulcers. Int. J. Low Extrem. Wounds 2009, 8, 11–18. [Google Scholar] [CrossRef] [PubMed]
  161. Karr, J. Utilization of living bilayered cell therapy (Apligraf) for heel ulcers. Adv. Skin Wound Care 2008, 21, 270–274. [Google Scholar] [CrossRef] [PubMed]
  162. Nie, C.; Yang, D.; Morris, S.F. Local delivery of adipose-derived stem cells via acellular dermal matrix as a scaffold: A new promising strategy to accelerate wound healing. Med. Hypotheses 2009, 72, 679–682. [Google Scholar] [CrossRef] [PubMed]
  163. Altman, A.M.; Chiu, E.S.; Bai, X.; Yan, Y.; Song, Y.H.; Newsome, R.E.; Alt, E.U. Human adipose-derived stem cells adhere to acellular dermal matrix. Aesthetic Plast. Surg. 2008, 32, 698–699. [Google Scholar] [CrossRef] [PubMed]
  164. Altman, A.M.; Matthias, N.; Yan, Y.; Song, Y.H.; Bai, X.; Chiu, E.S.; Slakey, D.P.; Alt, E.U. Dermal matrix as a carrier for in vivo delivery of human adipose-derived stem cells. Biomaterials 2008, 29, 1431–1442. [Google Scholar] [CrossRef] [PubMed]
  165. Levis, H.; Daniels, J.T. New technologies in limbal epithelial stem cell transplantation. Curr. Opin. Biotechnol. 2009, 20, 593–597. [Google Scholar] [CrossRef] [PubMed]
  166. Schwab, I.R. Cultured corneal epithelia for ocular surface disease. Trans. Am. Ophthalmol. Soc. 1999, 97, 891–986. [Google Scholar] [PubMed]
  167. Zakaria, N.; Koppen, C.; Van Tendeloo, V.; Berneman, Z.; Hopkinson, A.; Tassignon, M.J. Standardized limbal epithelial stem cell graft generation and transplantation. Tissue Eng. C Methods 2010, in presss. [Google Scholar]
  168. Shortt, A.J.; Secker, G.A.; Lomas, R.J.; Wilshaw, S.P.; Kearney, J.N.; Tuft, S.J.; Daniels, J.T. The effect of amniotic membrane preparation method on its ability to serve as a substrate for the ex-vivo expansion of limbal epithelial cells. Biomaterials 2009, 30, 1056–1065. [Google Scholar] [CrossRef] [PubMed]
  169. Dravida, S.; Gaddipati, S.; Griffith, M.; Merrett, K.; Lakshmi Madhira, S.; Sangwan, V.S.; Vemuganti, G.K. A biomimetic scaffold for culturing limbal stem cells: A promising alternative for clinical transplantation. J. Tissue Eng. Regen. Med. 2008, 2, 263–271. [Google Scholar] [CrossRef] [PubMed]
  170. Grueterich, M.; Espana, E.M.; Tseng, S.C. Ex vivo expansion of limbal epithelial stem cells: Amniotic membrane serving as a stem cell niche. Surv. Ophthalmol. 2003, 48, 631–646. [Google Scholar] [CrossRef] [PubMed]
  171. Griffith, M.; Jackson, W.B.; Lagali, N.; Merrett, K.; Li, F.; Fagerholm, P. Artificial corneas: A regenerative medicine approach. Eye (Lond) 2009, 23, 1985–1989. [Google Scholar] [CrossRef]
  172. Liu, Y.; Griffith, M.; Watsky, M.A.; Forrester, J.V.; Kuffova, L.; Grant, D.; Merrett, K.; Carlsson, D.J. Properties of porcine and recombinant human collagen matrices for optically clear tissue engineering applications. Biomacromolecules 2006, 7, 1819–1828. [Google Scholar] [CrossRef] [PubMed]
  173. Lagali, N.; Griffith, M.; Fagerholm, P.; Merrett, K.; Huynh, M.; Munger, R. Innervation of tissue-engineered recombinant human collagen-based corneal substitutes: A comparative in vivo confocal microscopy study. Invest. Ophthalmol. Vis. Sci. 2008, 49, 3895–3902. [Google Scholar] [CrossRef] [PubMed]
  174. Carrier, P.; Deschambeault, A.; Talbot, M.; Giasson, C.J.; Auger, F.A.; Guerin, S.L.; Germain, L. Characterization of wound reepithelialization using a new human tissue-engineered corneal wound healing model. Invest. Ophthalmol. Vis. Sci. 2008, 49, 1376–1385. [Google Scholar] [CrossRef] [PubMed]
  175. Rafat, M.; Matsuura, T.; Li, F.; Griffith, M. Surface modification of collagen-based artificial cornea for reduced endothelialization. J. Biomed. Mater. Res. A 2009, 88, 755–768. [Google Scholar] [CrossRef] [PubMed]
  176. Shekarriz, B.; Upadhyay, J.; Demirbilek, S.; Barthold, J.S.; Gonzalez, R. Surgical complications of bladder augmentation: Comparison between various enterocystoplasties in 133 patients. Urology 2000, 55, 123–128. [Google Scholar] [CrossRef] [PubMed]
  177. Mingin, G.C.; Stock, J.A.; Hanna, M.K. Gastrocystoplasty: Long-term complications in 22 patients. J. Urol. 1999, 162, 1122–1125. [Google Scholar] [CrossRef] [PubMed]
  178. Liu, Y.; Bharadwaj, S.; Lee, S.J.; Atala, A.; Zhang, Y. Optimization of a natural collagen scaffold to aid cell-matrix penetration for urologic tissue engineering. Biomaterials 2009, 30, 3865–3873. [Google Scholar] [CrossRef] [PubMed]
  179. Chen, B.S.; Zhang, S.L.; Geng, H.; Pan, J.; Chen, F. Ex vivo functional evaluation of isolated strips in BAMG tissue-engineered bladders. Int. J. Artif. Organs 2009, 32, 159–165. [Google Scholar] [PubMed]
  180. Parshotam Kumar, G.; Barker, A.; Ahmed, S.; Gerath, J.; Orford, J. Urinary bladder auto augmentation using INTEGRA((R)) and SURGISIS ((R)): An experimental model. Pediatr. Surg. Int. 2010, 26, 275–280. [Google Scholar] [CrossRef] [PubMed]
  181. Akbal, C.; Lee, S.D.; Packer, S.C.; Davis, M.M.; Rink, R.C.; Kaefer, M. Bladder augmentation with acellular dermal biomatrix in a diseased animal model. J. Urol. 2006, 176, 1706–1711. [Google Scholar] [CrossRef] [PubMed]
  182. Fiala, R.; Vidlar, A.; Vrtal, R.; Belej, K.; Student, V. Porcine small intestinal submucosa graft for repair of anterior urethral strictures. Eur. Urol. 2007, 51, 1702–1708; discussion 1708. [Google Scholar] [CrossRef] [PubMed]
  183. Farahat, Y.A.; Elbahnasy, A.M.; El-Gamal, O.M.; Ramadan, A.R.; El-Abd, S.A.; Taha, M.R. Endoscopic urethroplasty using small intestinal submucosal patch in cases of recurrent urethral stricture: A preliminary study. J. Endourol. 2009, 23, 2001–2005. [Google Scholar] [CrossRef] [PubMed]
  184. el-Kassaby, A.; AbouShwareb, T.; Atala, A. Randomized comparative study between buccal mucosal and acellular bladder matrix grafts in complex anterior urethral strictures. J. Urol. 2008, 179, 1432–1436. [Google Scholar] [CrossRef] [PubMed]
  185. Bouhout, S.; Perron, E.; Gauvin, R.; Bernard, G.; Ouellet, G.; Cattan, V.; Bolduc, S. In vitro Reconstruction of an autologous, watertight and resistant vesical equivalent. Tissue Eng. A 2010. [Google Scholar] [CrossRef]
  186. Atala, A.; Bauer, S.B.; Soker, S.; Yoo, J.J.; Retik, A.B. Tissue-engineered autologous bladders for patients needing cystoplasty. Lancet 2006, 367, 1241–1246. [Google Scholar] [CrossRef] [PubMed]
  187. Magnan, M.; Berthod, F.; Champigny, M.F.; Soucy, F.; Bolduc, S. In vitro reconstruction of a tissue-engineered endothelialized bladder from a single porcine biopsy. J. Pediatr. Urol. 2006, 2, 261–270. [Google Scholar] [CrossRef] [PubMed]
  188. Oberson, C.; Boubaker, A.; Ramseyer, P.; Meyrat, B.J.; Frey, P. Endoscopic and surgical treatment of vesico-ureteral reflux in children. Comparative long-term follow-up. Swiss Med. Wkly. 2007, 137, 471–475. [Google Scholar] [PubMed]
  189. Isom-Batz, G.; Zimmern, P.E. Collagen injection for female urinary incontinence after urethral or periurethral surgery. J. Urol. 2009, 181, 701–704. [Google Scholar] [CrossRef] [PubMed]
  190. Koduri, S.; Goldberg, R.P.; Kwon, C.; Dobrez, D.G.; Sand, P.K. Factors influencing the long-term success of periurethral collagen therapy in the office. Int. Urogynecol. J. Pelvic. Floor. Dysfunct. 2006, 17, 346–351. [Google Scholar] [CrossRef] [PubMed]
  191. Chamberlain, L.J.; Yannas, I.V.; Hsu, H.P.; Strichartz, G.; Spector, M. Collagen-GAG substrate enhances the quality of nerve regeneration through collagen tubes up to level of autograft. Exp. Neurol. 1998, 154, 315–329. [Google Scholar] [CrossRef] [PubMed]
  192. Archibald, S.J.; Krarup, C.; Shefner, J.; Li, S.T.; Madison, R.D. A collagen-based nerve guide conduit for peripheral nerve repair: An electrophysiological study of nerve regeneration in rodents and nonhuman primates. J. Comp. Neurol. 1991, 306, 685–696. [Google Scholar] [CrossRef] [PubMed]
  193. Colin, W.; Donoff, R.B. Nerve regeneration through collagen tubes. J. Dent. Res. 1984, 63, 987–993. [Google Scholar] [CrossRef] [PubMed]
  194. Hudson, T.W.; Zawko, S.; Deister, C.; Lundy, S.; Hu, C.Y.; Lee, K.; Schmidt, C.E. Optimized acellular nerve graft is immunologically tolerated and supports regeneration. Tissue Eng. 2004, 10, 1641–1651. [Google Scholar] [CrossRef] [PubMed]
  195. Madaghiele, M.; Sannino, A.; Yannas, I.V.; Spector, M. Collagen-based matrices with axially oriented pores. J. Biomed. Mater. Res. A 2008, 85, 757–767. [Google Scholar] [CrossRef] [PubMed]
  196. Bozkurt, A.; Brook, G.A.; Moellers, S.; Lassner, F.; Sellhaus, B.; Weis, J.; Woeltje, M.; Tank, J.; Beckmann, C.; Fuchs, P.; Damink, L.O.; Schugner, F.; Heschel, I.; Pallua, N. In vitro assessment of axonal growth using dorsal root ganglia explants in a novel three-dimensional collagen matrix. Tissue Eng. 2007, 13, 2971–2979. [Google Scholar] [CrossRef] [PubMed]
  197. Sun, W.; Lin, H.; Chen, B.; Zhao, W.; Zhao, Y.; Xiao, Z.; Dai, J. Collagen scaffolds loaded with collagen-binding NGF-beta accelerate ulcer healing. J. Biomed. Mater. Res. A 2009, 92A, 887–895. [Google Scholar]
  198. Sun, W.; Lin, H.; Chen, B.; Zhao, W.; Zhao, Y.; Dai, J. Promotion of peripheral nerve growth by collagen scaffolds loaded with collagen-targeting human nerve growth factor-beta. J. Biomed. Mater. Res. A 2007, 83, 1054–1061. [Google Scholar] [CrossRef] [PubMed]
  199. Marchesi, C.; Pluderi, M.; Colleoni, F.; Belicchi, M.; Meregalli, M.; Farini, A.; Parolini, D.; Draghi, L.; Fruguglietti, M.E.; Gavina, M.; Porretti, L.; Cattaneo, A.; Battistelli, M.; Prelle, A.; Moggio, M.; Borsa, S.; Bello, L.; Spagnoli, D.; Gaini, S.M.; Tanzi, M.C.; Bresolin, N.; Grimoldi, N.; Torrente, Y. Skin-derived stem cells transplanted into resorbable guides provide functional nerve regeneration after sciatic nerve resection. Glia 2007, 55, 425–438. [Google Scholar] [CrossRef] [PubMed]
  200. Bozkurt, A.; Deumens, R.; Beckmann, C.; Olde Damink, L.; Schugner, F.; Heschel, I.; Sellhaus, B.; Weis, J.; Jahnen-Dechent, W.; Brook, G.A.; Pallua, N. In vitro cell alignment obtained with a Schwann cell enriched microstructured nerve guide with longitudinal guidance channels. Biomaterials 2009, 30, 169–179. [Google Scholar] [CrossRef] [PubMed]
  201. Kemp, S.W.; Syed, S.; Walsh, W.; Zochodne, D.W.; Midha, R. Collagen nerve conduits promote enhanced axonal regeneration, schwann cell association, and neovascularization compared to silicone conduits. Tissue Eng. A 2009, 15, 1975–1988. [Google Scholar] [CrossRef]
  202. Blais, M.; Grenier, M.; Berthod, F. Improvement of nerve regeneration in tissue-engineered skin enriched with schwann cells. J. Invest. Dermatol. 2009, 129, 2895–2900. [Google Scholar] [CrossRef] [PubMed]
  203. Bentkover, S.H. The biology of facial fillers. Facial Plast. Surg. 2009, 25, 73–85. [Google Scholar] [CrossRef] [PubMed]
  204. Mao, J.; Stosich, M.S.; Moioli, E.; Lee, C.H.; Fu, S.; Bastian, B.; Eisig, S.; Zemnick, C.; Ascherman, J.; Wu, J.; Rohde, C.; Ahn, J. Facial Reconstruction by Biosurgery: Cell Transplantation vs. Cell Homing. Tissue Eng. B Rev. 2010, in press. [Google Scholar]
  205. Gurney, T.A.; Kim, D.W. Applications of porcine dermal collagen (ENDURAGen) in facial plastic surgery. Facial Plast. Surg. Clin. North Am. 2007, 15, 113–121. [Google Scholar] [CrossRef] [PubMed]
  206. Pons-Guiraud, A. Adverse reactions to injectable fillers. Ann. Dermatol. Venereol. 2008, 135, 171–174. [Google Scholar] [CrossRef]
  207. Ellis, D.A.; Segall, L. Review of non-FDA-approved fillers. Facial Plast. Surg. Clin. North Am. 2007, 15, 239–246. [Google Scholar] [CrossRef] [PubMed]
  208. Adhirajan, N.; Shanmugasundaram, N.; Shanmuganathan, S.; Babu, M. Collagen-based wound dressing for doxycycline delivery: in-vivo evaluation in an infected excisional wound model in rats. J. Pharm. Pharmacol. 2009, 61, 1617–1623. [Google Scholar] [CrossRef] [PubMed]
  209. Adhirajan, N.; Shanmugasundaram, N.; Shanmuganathan, S.; Babu, M. Functionally modified gelatin microspheres impregnated collagen scaffold as novel wound dressing to attenuate the proteases and bacterial growth. Eur. J. Pharm. Sci. 2009, 36, 235–245. [Google Scholar] [CrossRef] [PubMed]
  210. Sripriya, R.; Kumar, M.S.; Ahmed, M.R.; Sehgal, P.K. Collagen bilayer dressing with ciprofloxacin, an effective system for infected wound healing. J. Biomater. Sci. Polym. Ed. 2007, 18, 335–351. [Google Scholar] [CrossRef] [PubMed]
  211. Shanmugasundaram, N.; Sundaraseelan, J.; Uma, S.; Selvaraj, D.; Babu, M. Design and delivery of silver sulfadiazine from alginate microspheres-impregnated collagen scaffold. J. Biomed. Mater. Res. B Appl. Biomater. 2006, 77, 378–388. [Google Scholar] [CrossRef] [PubMed]
  212. Liyanage, S.H.; Purohit, G.S.; Frye, J.N.; Giordano, P. Anterior abdominal wall reconstruction with a Permacol implant. J. Plast. Reconstr. Aesthet. Surg. 2006, 59, 553–555. [Google Scholar] [CrossRef] [PubMed]
  213. Bellows, C.F.; Jian, W.; McHale, M.K.; Cardenas, D.; West, J.L.; Lerner, S.P.; Amiel, G.E. Blood vessel matrix: A new alternative for abdominal wall reconstruction. Hernia 2008, 12, 351–358. [Google Scholar] [CrossRef] [PubMed]
  214. Ansaloni, L.; Catena, F.; Gagliardi, S.; Gazzotti, F.; D'Alessandro, L.; Pinna, A.D. Hernia repair with porcine small-intestinal submucosa. Hernia 2007, 11, 321–326. [Google Scholar] [CrossRef] [PubMed]
  215. Takeshita, F.; Hokaiwado, N.; Honma, K.; Banas, A.; Ochiya, T. Local and systemic delivery of siRNAs for oligonucleotide therapy. Methods Mol. Biol. 2009, 487, 83–92. [Google Scholar] [PubMed]
  216. Takeshita, F.; Ochiya, T. Therapeutic potential of RNA interference against cancer. Cancer Sci. 2006, 97, 689–696. [Google Scholar] [CrossRef] [PubMed]
  217. Sano, A.; Maeda, M.; Nagahara, S.; Ochiya, T.; Honma, K.; Itoh, H.; Miyata, T.; Fujioka, K. Atelocollagen for protein and gene delivery. Adv. Drug Deliv. Rev. 2003, 55, 1651–1677. [Google Scholar] [CrossRef] [PubMed]
  218. Mulder, G.; Tallis, A.J.; Marshall, V.T.; Mozingo, D.; Phillips, L.; Pierce, G.F.; Chandler, L.A.; Sosnowski, B.K. Treatment of nonhealing diabetic foot ulcers with a platelet-derived growth factor gene-activated matrix (GAM501): Results of a phase 1/2 trial. Wound Repair Regen. 2009, 17, 772–779. [Google Scholar] [CrossRef] [PubMed]

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MDPI and ACS Style

Parenteau-Bareil, R.; Gauvin, R.; Berthod, F. Collagen-Based Biomaterials for Tissue Engineering Applications. Materials 2010, 3, 1863-1887.

AMA Style

Parenteau-Bareil R, Gauvin R, Berthod F. Collagen-Based Biomaterials for Tissue Engineering Applications. Materials. 2010; 3(3):1863-1887.

Chicago/Turabian Style

Parenteau-Bareil, Rémi, Robert Gauvin, and François Berthod. 2010. "Collagen-Based Biomaterials for Tissue Engineering Applications" Materials 3, no. 3: 1863-1887.

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