Influence of Parathyroid Hormone-Loaded PLGA Nanoparticles in Porous Scaffolds for Bone Regeneration

Biodegradable poly(lactide-co-glycolide) (PLGA) nanoparticles, containing human parathyroid hormone (PTH (1–34)), prepared by a modified double emulsion-solvent diffusion-evaporation method, were incorporated in porous freeze-dried chitosan-gelatin (CH-G) scaffolds. The PTH-loaded nanoparticles (NPTH) were characterised in terms of morphology, size, protein loading, release kinetics and in vitro assessment of biological activity of released PTH and cytocompatibility studies against clonal human osteoblast (hFOB) cells. Structural integrity of incorporated and released PTH from nanoparticles was found to be intact by using Tris-tricine SDS-PAGE. In vitro PTH release kinetics from PLGA nanoparticles were characterised by a burst release followed by a slow release phase for 3–4 weeks. The released PTH was biologically active as evidenced by the stimulated release of cyclic AMP from hFOB cells as well as increased mineralisation studies. Both in vitro and cell studies demonstrated that the PTH bioactivity was maintained during the fabrication of PLGA nanoparticles and upon release. Finally, a content of 33.3% w/w NPTHs was incorporated in CH-G scaffolds, showing an intermittent release during the first 10 days and, followed by a controlled release over 28 days of observation time. The increased expression of Alkaline Phosphatase levels on hFOB cells further confirmed the activity of intermittently released PTH from scaffolds.     

Experimental Construction of BMP2 and VEGF Gene Modified Tissue Engineering Bone in Vitro

The purpose of this study was to investigate the feasibility and advantages of constructing a novel tissue engineering bone, using β-tricalcium phosphate (β-TCP) and rat bone marrow mesenchymal stem cells (MSCs), modified with human bone morphogenetic protein 2 gene (hBMP2) and human vascular endothelial growth factor 165 gene (hVEGF165), through lentiviral transfection. Both genes were successfully co-expressed in the co-transfection group for up to eight weeks confirmed by enzyme-linked immunosorbent assay (ELISA). After seeding MSCs onto the scaffolds, scanning electron microscopy (SEM) observation showed that MSCs grew and proliferated well in co-transfection group at 7 and 14 days. There was no significant difference among all the groups in hoechst DNA assay for cell proliferation for 14 days after cell seeding (P > 0.05), but the highest alkaline phosphatase (ALP) activity was observed in the co-transfection group at 14 days after cell seeding (p < 0.01). These results demonstrated that it was advantageous to construct tissue engineering bone using β-TCP combined with MSCs lentivirally co-transfected with BMP2 and VEGF165, providing an innovative way for treating bone defects.     

Chitin and chitosan in selected biomedical applications

Chitin (CT), the well-known natural biopolymer and chitosan (CS) (bio-based or “artificial polymer”) are non-toxic, biodegradable and biocompatible in nature. The advantages of these biomaterials are such that, they can be easily processed into different forms such as membranes, sponges, gels, scaffolds, microparticles, nanoparticles and nanofibers for a variety of biomedical applications such as drug delivery, gene therapy, tissue engineering and wound healing. Present review focuses on the diverse applications of CT and CS membranes and scaffolds for drug delivery, tissue engineering and targeted regenerative medicine. The chitinous scaffolds of marine sponges’ origin are discussed here for the first time. These CT based scaffolds obtained from Porifera possess remarkable and unique properties such as hydration, interconnected channels and diverse structural architecture. This review will provide a brief overview of CT and CS membranes and scaffolds toward different kinds of delivery applications such as anticancer drug delivery, osteogenic drug delivery, and growth factor delivery, because of their inimitable release behavior, degradation profile, mucoadhesive nature, etc. The review also provides an overview of the key features of CT and CS membranes and scaffolds such as their biodegradability, cytocompatibility and mechanical properties toward applications in tissue engineering and wound healing.     

Stimuli-triggered structural engineering of synthetic and biological polymeric assemblies

Response to external stimuli is a fundamental and intrinsic behavior of living systems. There has been increasing interest for designing and constructing responsive polymeric superstructures by self-assembly. Stimuli-induced self-assembly and post-assembly triggering strategies provide an alternative approach for the manipulation of self-assembled architectures of either biological or synthetic polymeric materials. Stimuli-induced structural transformations may produce ensembles with new topologies or materials with exceptionally complex features inaccessible via conventional self-assembly processes. This is in contrast to materials that simply undergo stimuli-induced degradation, or disassembly processes. Since a variety of cellular processes depend on responses to environmental stimuli that lead to more complexity and increased function, and are related to structural transitions over the nano- to microscale, insights into stimuli-triggered morphogenesis can further deepen our understanding of cellular behaviors. Indeed, an understanding of these processes will likely inspire scientists to develop materials with advanced and tailored architectures for biosensing, diagnosis and therapy as well as other biomedical applications. Herein, we highlight state-of-the-art achievements in the stimuli-triggered structural manipulation of polymer assemblies. Furthermore, future developments in this nascent and growing field are briefly discussed.     

Biodegradable synthetic polymers: Preparation, functionalization and biomedical application

Biodegradable polymers have been widely used and have greatly promoted the development of biomedical fields because of their biocompatibility and biodegradability. The development of biotechnology and medical technology has set higher requirements for biomedical materials. Novel biodegradable polymers with specific properties are in great demand. Biodegradable polymers can be classified as natural or synthetic polymers according to the source. Synthetic biodegradable polymers have found more versatile and diverse biomedical applications owing to their tailorable designs or modifications. This review presents a comprehensive introduction to various types of synthetic biodegradable polymers with reactive groups and bioactive groups, and further describes their structure, preparation procedures and properties. The focus is on advances in the past decade in functionalization and responsive strategies of biodegradable polymers and their biomedical applications. The possible future developments of the materials are also discussed.     

Construction of functional aliphatic polycarbonates for biomedical applications

Aliphatic polycarbonates are one important kind of biodegradable polymers and have been commonly used as integral components of engineered tissues, medical devices and drug delivery systems. As far as the biomedical application is concerned, traditional aliphatic polycarbonates usually suffer from the strong hydrophobicity, deficient functionality, and insufficient compatibility with cell/organs. Consequently, the application is quite limited in scope. Due to the imparted appealing properties, aliphatic polycarbonates bearing specifically designed functional/reactive groups attract great interest from researchers in the recent years. The present review outlines the development up to date concerning the design and biomedical application of functional aliphatic polycarbonates, with an emphasis on their ring-opening (co)polymerization preparation.     

Chitosan—A versatile semi-synthetic polymer in biomedical applications

This review outlines the new developments on chitosan-based bioapplications. Over the last decade, functional biomaterials research has developed new drug delivery systems and improved scaffolds for regenerative medicine that is currently one of the most rapidly growing fields in the life sciences. The aim is to restore or replace damaged body parts or lost organs by transplanting supportive scaffolds with appropriate cells that in combination with biomolecules generate new tissue. This is a highly interdisciplinary field that encompasses polymer synthesis and modification, cell culturing, gene therapy, stem cell research, therapeutic cloning and tissue engineering. In this regard, chitosan, as a biopolymer derived macromolecular compound, has a major involvement. Chitosan is a polyelectrolyte with reactive functional groups, gel-forming capability, high adsorption capacity and biodegradability. In addition, it is innately biocompatible and non-toxic to living tissues as well as having antibacterial, antifungal and antitumor activity. These features highlight the suitability and extensive applications that chitosan has in medicine. Micro/nanoparticles and hydrogels are widely used in the design of chitosan-based therapeuticsystems. The chemical structure and relevant biological properties of chitosan for regenerative medicine have been summarized as well as the methods for the preparation of controlled drug release devices and their applications.