Biomimetic delivery of signals for bone tissue engineering

Bone tissue engineering is an exciting approach to directly repair bone defects or engineer bone tissue for transplantation.Biomaterials play a pivotal role in providing a template and extracellular environment to support regenerative cells and promote tissue regeneration. A variety of signaling cues have been identified to regulate cellular activity, tissue development, and the healing process. Numerous studies and trials have shown the promise of tissue engineering, but successful translations of bone tissue engineering research into clinical applications have been limited, due in part to a lack of optimal delivery systems for these signals. Biomedical engineers are therefore highly motivated to develop biomimetic drug delivery systems, which benefit from mimicking signaling molecule release or presentation by the native extracellular matrix during development or the natural healing process. Engineered biomimetic drug delivery systems aim to provide control over the location, timing, and release kinetics of the signal molecules according to the drug's physiochemical properties and specific biological mechanisms. This article reviews biomimetic strategies in signaling delivery for bone tissue engineering, with a focus on delivery systems rather than specific molecules. Both fundamental considerations and specific design strategies are discussed with examples of recent research progress, demonstrating the significance and potential of biomimetic delivery systems for bone tissue engineering.

Synthetic biodegradable functional polymers for tissue engineering:a brief review

Scaffolds play a crucial role in tissue engineering. Biodegradable polymers with great processing flexibility are the predominant scaffolding materials. Synthetic biodegradable polymers with well-defined structure and without immunological concerns associated with naturally derived polymers are widely used in tissue engineering. The synthetic biodegradable polymers that are widely used in tissue engineering, including polyesters, polyanhydrides, polyphosphazenes, polyurethane, and poly(glycerol sebacate) are summarized in this article. New developments in conducting polymers, photoresponsive polymers, amino-acid-based polymers, enzymatically degradable polymers, and peptide-activated polymers are also discussed. In addition to chemical functionalization, the scaffold designs that mimic the nano and micro features of the extracellular matrix(ECM) are presented as well, and composite and nanocomposite scaffolds are also reviewed.

Functionalized scaffolds to enhance tissue regeneration

Tissue engineering scaffolds play a vital role in regenerative medicine.It not only provides a temporary 3-dimensional support during tissue repair,but also regulates the cell behavior,such as cell adhesion,proliferation and differentiation.In this review,we summarize the development and trends of functional scaffolding biomaterials including electrically conducting hydrogels and nanocomposites of hydroxyapatite(HA)and bioactive glasses(BGs)with various biodegradable polymers.Furthermore,the progress on the fabrication of biomimetic nanofibrous scaffolds from conducting polymers and composites of HA and BG via electrospinning,deposition and thermally induced phase separation is discussed.Moreover,bioactive molecules and surface properties of scaffolds are very important during tissue repair.Bioactive molecule-releasing scaffolds and antimicrobial surface coatings for biomedical implants and scaffolds are also reviewed.

Hybrid polymer biomaterials for bone tissue regeneration

Native tissues possess unparalleled physiochemical and biological functions, which can be attributed to their hybrid polymer composition and intrinsic bioactivity. However, there are also various concerns or limitations over the use of natural materials derived from animals or cadavers, including the potential immunogenicity, pathogen transmission, batch to batch consistence and mismatch in properties for various applications. Therefore, there is an increasing interest in developing degradable hybrid polymer biomaterials with controlled properties for highly efficient biomedical applications. There have been efforts to mimic the extracellular protein structure such as nanofibrous and composite scaffolds, to functionalize scaffold surface for improved cellular interaction, to incorporate controlled biomolecule release capacity to impart biological signaling, and to vary physical properties of scaffolds to regulate cellular behavior. In this review, we highlight the design and synthesis of degradable hybrid polymer biomaterials and focus on recent developments in osteoconductive, elastomeric, photoluminescent and electroactive hybrid polymers. The review further exemplifies their applications for bone tissue regeneration.

Optimizing surface-engineered ultra-small gold nanoparticles for highly efficient miRNA delivery to enhance osteogenic differentiation of bone mesenchymal stromal cells

Regulation of osteogenic differentiation of bone mesenchymal stromal cells （BMSCs） plays a critical role in bone regeneration. As small non-coding RNAs, microRNAs （miRNAs） play an important role in stem cell differentiation through regulating target-mRNA expression. Unfortunately, highly efficient and safe delivery of miRNAs to BMSCs to regulate their osteogenic differentiation remains challenging. Conventional inorganic nanocrystals have shown increased toxicity owing to their larger size precluding renal clearance. Here, we developed novel, surface-engineered, ultra-small gold nanoparticles （USAuNPs, 〈10 nm） for use as highly efficient miR-5106-delivery systems to enable regulation of BMSC differentiation. We exploited the effects of AuNPs coated layer-by-layer with polyethylenimine （PEI） and liposomes （Lipo） to enhance miR-5106-delivery activity and subsequent BMSC differentiation capacity. The PEI- and Lipo-coated AuNPs （Au@PEI@Lipo） showed negligible cytotoxicity, good miRNA-5106-binding affinity, highly efficient delivery of miRNAs to BMSCs, and long-term miRNA expression （21 days）. Additionally, compared with commercial Lipofectamine 3000 and 25 kD PEI, the optimized Au@PEI@Lipo-miR-5106 nanocomplexes significantly enhanced BMSC differentiation into osteoblast-like cells through activation of the Sox9 transcription factor. Our findings reveal a promising strategy for the rational design of ultra-small inorganic nanoparticles as highly efficient miRNA-delivery platforms for tissue regeneration and disease therapy.