In tissue engineering, bioactive materials play an important role, providing structural support, cell regulation and establishing a suitable microenvironment to promote tissue regeneration. As the main component of extracellular matrix, collagen is an important natural bioactive material and it has been widely used in scientific research and clinical applications. Collagen is available from a wide range of animal origin, it can be produced by synthesis or through recombinant protein production systems. The use of pure collagen has inherent disadvantages in terms of physico-chemical properties. For this reason, a processed collagen in different ways can better match the specific requirements as biomaterial for tissue repair. Here, collagen may be used in bone/cartilage regeneration, skin regeneration, cardiovascular repair and other fields, by following different processing methods, including cross-linked collagen, complex, structured collagen, mineralized collagen, carrier and other forms, promoting the development of tissue engineering. This review summarizes a wide range of applications of collagen-based biomaterials and their recent progress in several tissue regeneration fields. Furthermore, the application prospect of bioactive materials based on collagen was outlooked, aiming at inspiring more new progress and advancements in tissue engineering research. Graphical Abstract

Living probiotics secrete bioactive substances to accelerate wound healing, but the clinical application of antibiotics inhibits the survival of probiotics. Inspired by the chelation of tannic acid and ferric ions,...

Nanostructured biomaterials that replicate natural bone architecture are expected to facilitate bone regeneration. Here, nanohydroxyapatite (nHAp) with vinyl surface modification is acquired by silicon-based coupling agent and photointegrated with methacrylic anhydride-modified gelatin to manufacture a chemically integrated 3D-printed hybrid bone scaffold (75.6 wt% solid content). This nanostructured procedure significantly increases its storage modulus by 19.43-fold (79.2 kPa) to construct a more stable mechanical structure. Furthermore, biofunctional hydrogel with biomimetic extracellular matrix is anchored onto the filament of 3D-printed hybrid scaffold (HGel-g-nHAp) by polyphenol-mediated multiple chemical reactions, which contributes to initiate early osteogenesis and angiogenesis by recruiting endogenous stem cells in situ. Significant ectopic mineral deposition is also observed in subcutaneously implanted nude mice with storage modulus enhancement of 25.3-fold after 30 days. Meanwhile, HGel-g-nHAp realizes substantial bone reconstruction in the rabbit cranial defect model, achieving 61.3% breaking load strength and 73.1% bone volume fractions in comparison to natural cranium 15 weeks after implantation. This optical integration strategy of vinyl modified nHAp provides a prospective structural design for regenerative 3D-printed bone scaffold.

Lesioned tissue requires synchronous control of disease and regeneration progression after surgery. It is necessary to develop therapeutic and regenerative scaffolds. Here, hyaluronic acid (HA) was esterified with benzyl groups to prepare hyaluronic acid derivative (HA-Bn) nanofibers via electrospinning. Electrospun membranes with average fiber diameters of 407.64 ± 124.8 nm (H400), 642.3 ± 228.76 nm (H600), and 841.09 ± 236.86 nm (H800) were obtained by adjusting the spinning parameters. These fibrous membranes had good biocompatibility, among which the H400 group could promote the proliferation and spread of L929 cells. Using the postoperative treatment of malignant skin melanoma as an example, the anticancer drug doxorubicin (DOX) was encapsulated in nanofibers via hybrid electrospinning. The UV spectroscopy of DOX-loaded nanofibers (HA-DOX) revealed that DOX was successfully encapsulated, and there was a π–π interaction between aromatic DOX and HA-Bn. The drug release profile confirmed the sustained release of about 90%, achieved within 7 days. In vitro cell experiments proved that the HA-DOX nanofiber had a considerable inhibitory effect on B16F10 cells. Therefore, the HA-Bn electrospun membrane could facilitate the potential regeneration of injured skin tissues and be incorporated with drugs to achieve therapeutic effects, offering a powerful approach to developing therapeutic and regenerative biomaterial.

Collagen‐based hydrogels have a significant impact on wound healing, but they suffer from structural instability and bacterial invasion in infected wounds. Here, electrospun nanofibers of esterified hyaluronan (HA‐Bn/T) are developed to immobilize the hydrophobic antibacterial drug tetracycline by π–π stacking interaction. Dopamine‐modified hyaluronan and HA‐Bn/T are employed simultaneously to stabilize the structure of collagen‐based hydrogel by chemically interweaving the collagen fibril network and decreasing the rate of collagen degradation. This renders it injectable for in situ gelation, with suitable skin adhesion properties and long‐lasting drug release capability. This hybridized interwoven hydrogel promotes the proliferation and migration of L929 cells and vascularization in vitro. It presents satisfactory antibacterial ability against Staphylococcus aureus and Escherichia coli. The structure also retains the functional protein environment provided by collagen fiber, inhibits the bacterial environment of infected wounds, and modulates local inflammation, resulting in neovascularization, collagen deposition, and partial follicular regeneration. This strategy offers a new solution for infected wound healing.