Limited stem cells, poor stretchability and mismatched interface fusion have plagued the reconstruction of cranial defects by cell-free scaffolds. Here, we designed an instantly fixable and self-adaptive scaffold by dopamine-modified hyaluronic acid chelating Ca²⁺ of the microhydroxyapatite surface and bonding type I collagen to highly simulate the natural bony matrix. It presents a good mechanical match and interface integration by appropriate calcium chelation, and responds to external stress by flexible deformation. Meanwhile, the appropriate matrix microenvironment regulates macrophage M2 polarization and recruits endogenous stem cells. This scaffold promotes the proliferation and osteogenic differentiation of BMSCs in vitro, as well as significant ectopic mineralization and angiogenesis. Transcriptome analysis confirmed the upregulation of relevant genes and signalling pathways was associated with M2 macrophage activation, endogenous stem cell recruitment, angiogenesis and osteogenesis. Together, the scaffold realized 97 and 72% bone cover areas after 12 weeks in cranial defect models of rabbit (Φ = 9 mm) and beagle dog (Φ = 15 mm), respectively.

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, we developed a metal-phenolic self-assembly shielded probiotic (Lactobacillus reuteri, L. reuteri@FeTA) to prevent interference from antibiotics. Here, a superimposing layer was formed on the surface of L. reuteri to adsorb and inactivate antibiotics. These shielded probiotics were loaded into an injectable hydrogel (Gel/L@FeTA) formed by carboxylated chitosan and oxidized hyaluronan. The Gel/L@FeTA aided the survival of probiotics and supported the continuous secretion of lactic acid to perform biological functions in an environment containing gentamicin. Furthermore, the Gel/L@FeTA hydrogels presented a better performance than the Gel/L in inflammatory regulation, angiogenesis, and tissue regeneration both in vitro and in vivo in the presence of antibiotics. Hence, a new method for designing probiotic-based biomaterials for clinical wound management is provided.