Recent advances in regenerative biomaterials

Abstract

Nowadays, biomaterials have evolved from the inert supports or functional substitutes to the bioactive materials able to trigger or promote the regenerative potential of tissues. The interdisciplinary progress has broadened the definition of 'biomaterials', and a typical new insight is the concept of tissue induction biomaterials. The term 'regenerative biomaterials' and thus the contents of this article are relevant to yet beyond tissue induction biomaterials. This review summarizes the recent progress of medical materials including metals, ceramics, hydrogels, other polymers and bio-derived materials. As the application aspects are concerned, this article introduces regenerative biomaterials for bone and cartilage regeneration, cardiovascular repair, 3D bioprinting, wound healing and medical cosmetology. Cell-biomaterial interactions are highlighted. Since the global pandemic of coronavirus disease 2019, the review particularly mentions biomaterials for public health emergency. In the last section, perspectives are suggested: (i) creation of new materials is the source of innovation; (ii) modification of existing materials is an effective strategy for performance improvement; (iii) biomaterial degradation and tissue regeneration are required to be harmonious with each other; (iv) host responses can significantly influence the clinical outcomes; (v) the long-term outcomes should be paid more attention to; (vi) the noninvasive approaches for monitoring in vivo dynamic evolution are required to be developed; (vii) public health emergencies call for more research and development of biomaterials; and (viii) clinical translation needs to be pushed forward in a full-chain way. In the future, more new insights are expected to be shed into the brilliant field-regenerative biomaterials.

Keywords: medical material; regenerative biomaterial; tissue induction biomaterial; tissue regeneration.

Graphical abstract

Figure 1.

Different sources and applications of regenerative biomaterials.

Figure 2.

Metal and ceramic implants. (A) A fibrinogen-modified titanium alloy as a model material for an orthopedic percutaneous medical device. Reproduced from Ref. [36] with permission of Royal Society of Chemistry, © 2022. (B) Porous CaP ceramic scaffolds with distinct structures fabricated via digital light processing (DLP)-based 3D printing. Reproduced from Ref. [37] with permission of Oxford Press, © 2022.

Figure 3.

Hydrogels used in 3D printing. (A) Schematic diagrams of the key material properties to enable the continuous 3D-printing of the bilayered hydrogel scaffold. Reproduced from Ref. [129] with permission of Wiley-VCH, © 2020. (B) Schematic and photographs showing two-photon crosslinking of a hydrogel into dermis across the epidermis. Scale bars, 100 µm. Adapted from Ref. [133] with permission of Springer Nature, © 2022.

Figure 4.

Some polymer-based biomaterials with potential of clinical translation. (A) A patient case of 3D-printed polymeric ‘clear’ aligners. Reproduced from Ref. [197] with permission of Oxford University Press, © 2022. (B) A gastrointestinal (GI) patch for sutureless repair of gastrointestinal defects. Adapted from Ref. [198] with permission of the American Association for the Advancement of Science, © 2022.

Figure 5.

Hierarchical structure of the natural bone to stimulate the design of bone-regenerated biomaterials. The nature bone is composed of hierarchically arranged collagen fibrils and inorganic minerals, which can be mimicked to some extents in fabrication of 3D scaffolds using polymer-ceramic nanocomposites. Reproduced from Ref. [222] with permission of Springer Nature, © 2020.

Figure 6.

Noninvasive clinical evaluation of cartilage regeneration. Patients who experienced arthroscopic surgery for collecting autologous chondrocytes would accept matrix-induced autologous chondrocyte implantation (MACI) for cartilage regeneration, and the MRI is a feasible semi-quantitative yet noninvasive way for clinical follow-up. T1 (left) is the spin–lattice relaxation time with respect to longitudinal relaxation; T2 (right) is the spin–spin relaxation time with respect to transverse relaxation. Adapted from Ref. [265] with permission of Oxford University Press, © 2021.

Figure 7.

Implants for cardiovascular repair. (A) Using a polymer coating to accelerate the corrosion of iron by fabrication of a metal–polymer composite stent (MPS). Reproduced from Ref. [275] with permission of Elsevier, © 2021. (B) Surface modification of nitinol to enhance cell migration and the corresponding left atrial appendage (LAA) occluder with nanocoating. Reproduced from Ref. [58] with permission of American Chemical Society, © 2020.

Figure 8.

Biomaterials for being printed together with cells. (A) Schwann cell (SC)-neural stem cell (NSC) core–shell alginate hydrogel fibers fabricated via coaxial extrusion. Reproduced from Ref. [303] with permission of Oxford University Press, © 2021. (B) Volumetric bioprinting based on light projection using cell-laden gelMA PBS solution as bioink. Adapted from Ref. [304] with permission of Wiley-VCH, © 2019.

Figure 9.

Biomaterials for medical cosmetology: an intelligent paper-free sprayable skin mask based on environmental-friendly thermogel and its first clinical research. Reproduced from Ref. [327] with permission of Wiley-VCH, © 2022.

Figure 10.

Biomaterials platform for regenerative medicine delivery. (A) The drug exhibit spatial distribution between different administrations for wound healing including miniaturized needle array (i), topical administration (ii) and liquid jet injector (iii). Adapted from Ref. [357] with permission of Wiley-VCH, © 2021. (B) Orally dosed milli-injector capsules enable nucleic acid delivery to swine stomachs. The right part shows hematoxylin and eosin-stained histology (upper) and immunohistochemistry histology (lower) stained against RNA encoding Cre recombinase enzyme. Scale bars indicate 200 mm. Adapted from Ref. [358] with permission of Elsevier, © 2022.

Figure 11.

Biomaterials associated with COVID-19. (A) A mask equipped with a COVID-19 detected sensor. Adapted from Ref. [364] with permission of Springer Nature, © 2021. (B) An anticoagulant biomimetic gas exchange membrane used for ECMO. Reproduced from Ref. [365] with permission of Elsevier, © 2022.

Figure 12.

Lipid nanoparticles for COVID-19 mRNA vaccines. Reproduced from Ref. [375] with permission of Springer Nature, © 2021.

Figure 13.

The effects of nanopattern on cell adhesion and migration. (A) The effects of RGD nanospacing on cell migration and its relation to cell adhesion. Reproduced from Ref. [411] with permission of Elsevier, © 2020. (B) The migration of different type cells on biomaterials adjusted by RGD nanospacing. Reproduced from Ref. [412] with permission of American Chemical Society, © 2021.

Figure 14.

Immunomodulatory hydrogel. Reproduced from Ref. [450] with permission of Wiley-VCH, © 2021.

Figure 15.

Perspective key issues regarding the development of regenerative biomaterials.