Collagen Type I Biomaterials as Scaffolds for Bone Tissue Engineering

Abstract

Collagen type I is the main organic constituent of the bone extracellular matrix and has been used for decades as scaffolding material in bone tissue engineering approaches when autografts are not feasible. Polymeric collagen can be easily isolated from various animal sources and can be processed in a great number of ways to manufacture biomaterials in the form of sponges, particles, or hydrogels, among others, for different applications. Despite its great biocompatibility and osteoconductivity, collagen type I also has some drawbacks, such as its high biodegradability, low mechanical strength, and lack of osteoinductive activity. Therefore, many attempts have been made to improve the collagen type I-based implants for bone tissue engineering. This review aims to summarize the current status of collagen type I as a biomaterial for bone tissue engineering, as well as to highlight some of the main efforts that have been made recently towards designing and producing collagen implants to improve bone regeneration.

Keywords: bone tissue engineering; collagen; growth factors; peptides; scaffolds.

Figure 1

Schematic illustration of the diamond concept, showing the five elements that an ideal bone tissue engineering construct should provide.

Figure 2

Timeline showing some of the major milestones in the development of collagen-based scaffolds for bone tissue engineering (BTE).

Figure 3

Characterization of a double-crosslinked atelocollagen sponge. (A) STEM images of negatively stained atelocollagen nanofibrils, showing an axial periodicity of 67 nm. (B) Adhesion and proliferation of MC3T3-E1 preosteoblasts on double-crosslinked atelocollagen sponges (DColS-0.0015G, ⯀) or atelocollagen sponges only crosslinked by a dehydrothermal method (DColS, ♦). Mean ± standard deviation. *** p < 0.001. (C) hematoxylin-eosin staining of histological sections of intramuscular ectopic implants. DColS (a) and DColS-0.0015G (b) sponges were loaded with 600 ng of BMP-2 and implanted for 21 days. Only the DColS-0.0015G scaffolds were able to support osteogenesis. s: collagen; t: bone trabeculae; arrows: osteocytes. Modified with permission from [80].

Figure 4

Schematic representation of different approaches for administering bioactive molecules in/on a collagen-based biomaterial for tissue engineering purposes: adsorption (a), entrapment (b), covalent linkage (with or without controlled release, (c,d) or specific binding through collagen binding domains (e).

Figure 5

Collagen binding of a rhBMP2-CBD chimeric growth factor. Collagen type I sponges were loaded with different amounts of rhBMP-2 or rhBMP2-CBD, let dry and washed with PBS for 7 days. Molecules that remained bound to the sponges were detected using an anti-BMP-2 antibody. Modified from [107].

Figure 6

Biological activity of a collagen binding domain-Arg-Gly-Asp (CBD-RGD) synthetic peptide. (A) Schematic representation of the CBD-RGD peptide. (B) Ectopic bone formation in rats. Collagen type I sponges were functionalized with the CBD-RGD peptide (a,b) or not (c,d), loaded with 300 ng of BMP-2 and intramuscularly implanted in rats for 21 days. Upper images (a,c) are hematoxylin-eosin stained sections of the implants showing mature bone trabeculae in the sponges that had been functionalized with CBD-RGD. Lower images (b,d) correspond to anti-osteopontin immunohistochemistry. Arrows: bone trabeculae containing osteoblasts. (C) Calcium content of the recovered ectopic implants. No detectable calcium could be found within the non-fuctionalized implants. Contrarily, a significant amount of calcium was measured in the ectopic implants after 21 days. * p ≤ 0.01. Modified from [113].