Fengxuan Han

Cellular modulation by the elasticity of biomaterials

The behaviors and functions of individual cells, fundamental to the complexity of multicellular organisms, are regulated by their integrated response to a variety of environmental cues such as soluble factors, extracellular matrix (ECM)-mediated signals, and cell-cell interactions. Among these cues, the biomechanical feature of the ECM, represented by its elasticity, has been increasingly recognized as a dominating factor of cell fate. This review article aims to provide an overview of the general principles and recent advances in the field of matrix elasticity-dependent regulation of cellular activities and functions, the underlying biomechanical and molecular mechanisms, as well as pathophysiological implications. A discussion is also provided as to how material design strategies can be used to control the local microenvironment of stem cells to direct their lineage commitment and functions toward tissue development and regeneration.

3D bioactive composite scaffolds for bone tissue engineering

Bone is the second most commonly transplanted tissue worldwide, with over four million operations using bone grafts or bone substitute materials annually to treat bone defects. However, significant limitations affect current treatment options and clinical demand for bone grafts continues to rise due to conditions such as trauma, cancer, infection and arthritis. Developing bioactive three-dimensional (3D) scaffolds to support bone regeneration has therefore become a key area of focus within bone tissue engineering (BTE). A variety of materials and manufacturing methods including 3D printing have been used to create novel alternatives to traditional bone grafts. However, individual groups of materials including polymers, ceramics and hydrogels have been unable to fully replicate the properties of bone when used alone. Favourable material properties can be combined and bioactivity improved when groups of materials are used together in composite 3D scaffolds. This review will therefore consider the ideal properties of bioactive composite 3D scaffolds and examine recent use of polymers, hydrogels, metals, ceramics and bio-glasses in BTE. Scaffold fabrication methodology, mechanical performance, biocompatibility, bioactivity, and potential clinical translations will be discussed.

Electrospun Poly(l-lactide)/Poly(ethylene glycol) Scaffolds Seeded with Human Amniotic Mesenchymal Stem Cells for Urethral Epithelium Repair

Tissue engineering-based urethral replacement holds potential for repairing large segmental urethral defects, which remains a great challenge at present. This study aims to explore the potential of combining biodegradable poly(l-lactide) (PLLA)/poly(ethylene glycol) (PEG) scaffolds and human amniotic mesenchymal cells (hAMSCs) for repairing urethral defects. PLLA/PEG fibrous scaffolds with various PEG fractions were fabricated via electrospinning. The scaffolds were then seeded with hAMSCs prior to implantation in New Zealand male rabbits that had 2.0 cm-long defects in the urethras. The rabbits were randomly divided into three groups. In group A, hAMSCs were grown on PLLA/PEG scaffolds for two days and then implanted to the urethral defects. In group B, only the PLLA/PEG scaffolds were used to rebuild the rabbit urethral defect. In group C, the urethral defect was reconstructed using a regular urethral reparation technique. The repair efficacy was compared among the three groups by examining the urethral morphology, tissue reconstruction, luminal patency, and complication incidence (including calculus formation, urinary fistula, and urethral stricture) using histological evaluation and urethral radiography methods. Findings from this study indicate that hAMSCs-loaded PLLA/PEG scaffolds resulted in the best urethral defect repair in rabbits, which predicts the promising application of a tissue engineering approach for urethral repair.

Mussel-inspired deposition of copper on titanium for bacterial inhibition and enhanced osseointegration in a periprosthetic infection model

Periprosthetic infection represents one of the most devastating complications in orthopedic surgeries. Implants that have both anti-bacterial and bone-forming capability and may function to simultaneously clear infection and repair bone defect, therefore, are highly desirable. In this study, titanium (Ti) substrates were fabricated deposited with different amounts of copper (Cu) using polydopamine (PDA)-based chemical modification technology. In vitro, Ti implants that were treated with PDA and deposited with Cu (Ti-PDA-Cu) showed excellent antibacterial performance against both S. aureus and E. coli compared with pristine Ti. They also markedly promoted adhesion and spreading of MC3T3-E1 cells, implying good biocompatibility of such Ti-PDA-Cu materials. In vivo, results from an animal model of implant-related osteomyelitis clearly demonstrated that Ti-PDA-Cu implants not only effectively inhibited bacterial infection, but also promoted osseointegration at the bone/implant interface. Taken together, these findings show that Ti-PDA-Cu possesses outstanding biocompatibility and antibacterial activity, and are candidate materials for preventing periprosthetic infection.

In situ silk fibroin-mediated crystal formation of octacalcium phosphate and its application in bone repair

The development of an ideal scaffold material is critical for the repair of bone defects. Being an important precursor of the mineralized matrix of bone tissue, octacalcium phosphate (OCP) has been considered a promising bone substitute. However, its application is largely limited due to the thermodynamical instability and poor processability of it. In this study, OCP was prepared by co-precipitation in the presence of small amount of silk fibroin (SF), which regulated the crystallization of OCP and led to the formation of SF-OCP complex. The diameters of OCP crystals in OCP, 0.1SF-OCP, 0.3SF-OCP and 1SF-OCP complexes were 489.0 ± 399.1 nm, 102.2 ± 50.7 nm, 94.7 ± 48.4 nm and 223.7 ± 167.6 nm, respectively. However, the shape of OCP crystals did not apparently change by the presence of SF. Further, porous SF/OCP composite scaffolds with pore size of 111.9 ± 33.1 μm were prepared, in which small crystals of SF-OCP complex were embedded in a SF matrix. MC3T3-E1 cells could attach and proliferate well on both the rugged surfaces and the pores of SF/OCP scaffolds, indicating their decent biocompatibility. Further, SF/OCP scaffolds markedly promoted bone regeneration in a rat calvarial critical-sized defect model. Both micro-CT and H&E characterizations showed that bone formation not only occurred around the scaffolds, but also penetrated into their center. Therefore, such SF/OCP composite scaffolds may have potential applications in bone tissue engineering.

Calcium Phosphate-Silk Fibroin Composites: Bone Cement and Beyond

Calcium phosphate cements (CPCs) are promising substitute materials for current nonbiodegradable poly(methyl methacrylate)-based bone cements due to their outstanding biocompatibility, biodegradability, and osteoconductivity. However, the applications of calcium phosphates (CaPs) are relatively limited due to the inferior mechanical strength. Silk fibroin (SF), a natural fibrous protein that originated from silkworm or spider which has good biocompatibility, biodegradability, and mechanical properties, has been used to reinforce the mechanical properties and improve the performance of CPCs. In addition to bone cement, CaP-SF composites have also been used as bone-repairing materials and carrier systems. In this chapter, we aim to provide a brief overview of recent progress in the use of CaP-SF composites as bone cement and for other purposes. The properties, processing techniques, and applications of CaPs and SF are first introduced, and the emerging challenges for CPCs are also discussed. Then the application of CaP-SFs as reinforced bone cements as well as the reinforcing mechanisms is reviewed. Finally, other applications of CaP-SF composites in bone tissue engineering are also discussed. We also provide our perspectives on the future development of CaP-SF composites for clinical applications.

The “Magnesium Sacrifice” Strategy Enables PMMA Bone Cement Partial Biodegradability and Osseointegration Potential

Poly (methyl methacrylate) (PMMA)-based bone cements are the most commonly used injectable orthopedic materials due to their excellent injectability and mechanical properties. However, their poor biocompatibility and excessive stiffness may cause complications such as aseptic implant loosening and stress shielding. In this study, we aimed to develop a new type of partially biodegradable composite bone cement by incorporating magnesium (Mg) microspheres, known as “Mg sacrifices” (MgSs), in the PMMA matrix. Being sensitive to the physiological environment, the MgSs in PMMA could gradually degrade to produce bioactive Mg ions and, meanwhile, result in an interconnected macroporous structure within the cement matrix. The mechanical properties, solidification, and biocompatibility, both in vitro and in vivo, of PMMA–Mg bone cement were characterized. Interestingly, the incorporation of Mg microspheres did not markedly affect the mechanical strength of bone cement. However, the maximum temperature upon setting of bone cement decreased. This partially biodegradable composite bone cement showed good biocompatibility in vitro. In the in vivo study, considerable bony ingrowth occurred in the pores upon MgS degradation. Together, the findings from this study indicate that such partially biodegradable PMMA–Mg composite may be ideal bone cement for minimally invasive orthopedic surgeries such as vertebroplasty and kyphoplasty.

Antibacterial activity and osseointegration of silver-coated poly(ether ether ketone) prepared using the polydopamine-assisted deposition technique

Poly(ether ether ketone) (PEEK) is a popular orthopaedic implant material due to the outstanding biocompatibility and mechanical properties. However, bacterial infections and aseptic loosening during implantation can cause many clinical problems that may eventually lead to implant failure. Therefore, endowing implants with antibacterial functions plays an important role in promoting integration between implants and bone tissue and ultimately, in successful implantation. This study aimed to develop a biocompatible and antibacterial coating for PEEK implants using polydopamine (PDA)-based surface modification technology and subsequent deposition of silver (Ag) nanoparticles (PEEK-PDA-Ag). Formation of Ag nanoparticles was clearly observed on the surface of PEEK-PDA-Ag using scanning electron microscopy. PEEK-PDA-Ag showed low toxicity to MC3T3-E1 cells. It exhibited outstanding antibacterial properties against both S. aureus and E. coli in vitro as well as decent antibacterial performance in vivo. In addition, in vivo studies demonstrated good osseointegration of PEEK-PDA-Ag implants, as shown by micro-CT evaluation and push-out tests. Together, the findings from this study indicate that the facilely prepared PEEK-PDA-Ag substrates possess considerable biocompatibility and antibacterial properties, permitting their potential use as a promising orthopaedic implant material.