Nowadays, there are still numerous challenges for well-known biomedical applications, such as tissue engineering (TE), wound healing and controlled drug delivery, which must be faced and solved. Hydrogels have been proposed as excellent candidates for these applications, as they have promising properties for the mentioned applications, including biocompatibility, biodegradability, great absorption capacity and tunable mechanical properties. However, depending on the material or the manufacturing method, the resulting hydrogel may not be up to the specific task for which it is designed, thus there are different approaches proposed to enhance hydrogel performance for the requirements of the application in question. The main purpose of this review article was to summarize the most recent trends of hydrogel technology, going through the most used polymeric materials and the most popular hydrogel synthesis methods in recent years, including different strategies of enhancing hydrogels’ properties, such as cross-linking and the manufacture of composite hydrogels. In addition, the secondary objective of this review was to briefly discuss other novel applications of hydrogels that have been proposed in the past few years which have drawn a lot of attention.

/pdf/novel-trends-in-hydrogel-development-for-biomedical-1fldsvdq.pdf

Novel Trends in Hydrogel Development for Biomedical Applications: A Review

The powder-based 3D printed alloys on titanium-based biomaterial applications: A review

Bone is a natural composite of collagen protein and the mineral hydroxyapatite. The structure of bone is known to be important to its load-bearing characteristics, but relatively little is known about this structure or the mechanism that govern deformation at the molecular scale. Here we perform full-atomistic calculations of the three-dimensional molecular structure of a mineralized collagen protein matrix to try to better understand its mechanical characteristics under tensile loading at various mineral densities. We find that as the mineral density increases, the tensile modulus of the network increases monotonically and well beyond that of pure collagen fibrils. Our results suggest that the mineral crystals within this network bears up to four times the stress of the collagen fibrils, whereas the collagen is predominantly responsible for the material’s deformation response. These findings reveal the mechanism by which bone is able to achieve superior energy dissipation and fracture resistance characteristics beyond its individual constituents.

Molecular mechanics of mineralized collagen fibrils in bone

Trauma and bone loss from infections, tumors, and congenital diseases make bone repair and regeneration the greatest challenges in orthopedic, craniofacial, and plastic surgeries. The shortage of donors, intrinsic limitations, and complications in transplantation have led to more focus and interest in regenerative medicine. Structures that closely mimic bone tissue can be produced by this unique technology. The steady development of three-dimensional (3D)-printed bone tissue engineering scaffold therapy has played an important role in achieving the desired goal. Bioceramic scaffolds are widely studied and appear to be the most promising solution. In addition, 3D printing technology can simulate mechanical and biological surface properties and print with high precision complex internal and external structures to match their functional properties. Inkjet, extrusion, and light-based 3D printing are among the rapidly advancing bone bioprinting technologies. Furthermore, stem cell therapy has recently shown an important role in this field, although large tissue defects are difficult to fill by injection alone. The combination of 3D-printed bone tissue engineering scaffolds with stem cells has shown very promising results. Therefore, biocompatible artificial tissue engineering with living cells is the key element required for clinical applications where there is a high demand for bone defect repair. Furthermore, the emergence of various advanced manufacturing technologies has made the form of biomaterials and their functions, composition, and structure more diversified, and manifold. The importance of this article lies in that it aims to briefly review the main principles and characteristics of the currently available methods in orthopedic bioprinting technology to prepare bioceramic scaffolds, and finally discuss the challenges and prospects for applications in this promising and vital field.

https://www.mdpi.com/2075-1729/12/6/903/pdf?version=1655375812

Bone Tissue Engineering through 3D Bioprinting of Bioceramic Scaffolds: A Review and Update

At present, bone nonunion and delayed union are still difficult problems in orthopaedics. Since the discovery of bone morphogenetic protein (BMP), it has been widely used in various studies due to its powerful role in promoting osteogenesis and chondrogenesis. Current results show that BMPs can promote healing of bone defects and reduce the occurrence of complications. However, the mechanism of BMP in vivo still needs to be explored, and application of BMP alone to a bone defect site cannot achieve good therapeutic effects. It is particularly important to modify implants to carry BMP to achieve slow and sustained release effects by taking advantage of the nature of the implant. This review aims to explain the mechanism of BMP action in vivo, its biological function, and how BMP can be applied to orthopaedic implants to effectively stimulate bone healing in the long term. Notably, implantation of a system that allows sustained release of BMP can provide an effective method to treat bone nonunion and delayed bone healing in the clinic.

Application of BMP in Bone Tissue Engineering

Collagen-based biomaterials for bone tissue engineering

Tumor resection and treatment of trauma-related regional large bone defects have major challenges in the field of orthopedics. Scaffolds that treat bone defects are the focus of bone tissue engineering. 3D printing porous titanium alloy scaffolds, prepared via electron beam melting (EBM) technology, possess customized structure and strength. The addition of a growth factor coating to the scaffold introduces a specific form of biological activation. Vascular endothelial growth factor (VEGF) is key to angiogenesis and osteogenesis in vivo. We designed a porous titanium alloy scaffold/thermosensitive collagen hydrogel system, equipped with VEGF, to promote local osseointegration and angiogenesis. We also verified the VEGF release via thermosensitive collagen and proliferation and induction of the human umbilical vein endothelial cells (HUVECs) via the composite system in vitro. In vivo, using micro-CT, histology, and immunohistochemistry analysis, we confirmed that the composite scaffold aids in angiogenesis-mediated bone regeneration, and promotes significantly more bone integration. We also discovered that the composite scaffold has excellent biocompatibility, provides bioactive VEGF for angiogenesis and osteointegration, and provides an important theoretical basis for the restoration of local blood supply and strengthening of bone integration.

Sustained Release of VEGF to Promote Angiogenesis and Osteointegration of Three-Dimensional Printed Biomimetic Titanium Alloy Implants

Three-dimensionally printed porous biomimetic composite for sustained release of recombinant human bone morphogenetic protein 9 to promote osteointegration

The invention is applicable to the field of biomedical materials, and provides a method for improving the biological activity of a titanium alloy material, the titanium alloy material and application.The method comprises the following steps: preprocessing a titanium alloy material; and injecting the temperature-sensitive collagen doped with the bone morphogenetic protein 9 into pores of the preprocessed titanium alloy material, wherein the titanium alloy material is a 3D printed porous titanium alloy material. The temperature-sensitive collagen doped with the bone morphogenetic protein 9 is implanted into pores and the surface of the 3D printing porous titanium alloy material, the temperature-sensitive collagen is used as a carrier for providing controlled release of the bone morphogeneticprotein 9, the biological activity of the surface of the titanium alloy material can be enhanced, and the bone ingrowth and osseointegration capacity of the titanium alloy material can be effectivelyimproved.

Liwei Zhu

Papers

Collagen-based biomaterials for bone tissue engineering

Sustained Release of VEGF to Promote Angiogenesis and Osteointegration of Three-Dimensional Printed Biomimetic Titanium Alloy Implants

Three-dimensionally printed porous biomimetic composite for sustained release of recombinant human bone morphogenetic protein 9 to promote osteointegration

Method for improving biological activity of titanium alloy material, titanium alloy material and application