Surface Functionalization of Poly(l-lactide-co-glycolide) Membranes with RGD-Grafted Poly(2-oxazoline) for Periodontal Tissue Engineering

Bone tissue defects resulting from periodontal disease are often treated using guided tissue regeneration (GTR). The barrier membranes utilized here should prevent soft tissue infiltration into the bony defect and simultaneously support bone regeneration. In this study, we designed a degradable poly(l-lactide-co-glycolide) (PLGA) membrane that was surface-modified with cell adhesive arginine-glycine-aspartic acid (RGD) motifs. For a novel method of membrane manufacture, the RGD motifs were coupled with the non-ionic amphiphilic polymer poly(2-oxazoline) (POx). The RGD-containing membranes were then prepared by solvent casting of PLGA, POx coupled with RGD (POx_RGD), and poly(ethylene glycol) (PEG) solution in methylene chloride (DCM), followed by DCM evaporation and PEG leaching. Successful coupling of RGD to POx was confirmed spectroscopically by Raman, Fourier transform infrared in attenuated reflection mode (FTIR-ATR), and X-ray photoelectron (XPS) spectroscopy, while successful immobilization of POx_RGD on the membrane surface was confirmed by XPS and FTIR-ATR. The resulting membranes had an asymmetric microstructure, as shown by scanning electron microscopy (SEM), where the glass-cured surface was more porous and had a higher surface area then the air-cured surface. The higher porosity should support bone tissue regeneration, while the air-cured side is more suited to preventing soft tissue infiltration. The behavior of osteoblast-like cells on PLGA membranes modified with POx_RGD was compared to cell behavior on PLGA foil, non-modified PLGA membranes, or PLGA membranes modified only with POx. For this, MG-63 cells were cultured for 4, 24, and 96 h on the membranes and analyzed by metabolic activity tests, live/dead staining, and fluorescent staining of actin fibers. The results showed bone cell adhesion, proliferation, and viability to be the highest on membranes modified with POx_RGD, making them possible candidates for GTR applications in periodontology and in bone tissue engineering.

Effect of Different Preparation Conditions On The Properties of Bamboo Fiber-Based Bioactive Composite Membrane

A novel nano-hydroxyapatite/bamboo fiber (n-HA/BF) bioactive composite membrane was obtained by a simple casting technique. The membrane forming mechanism and the effects of different forming membrane methods, drying methods and n-HA amounts on the properties of n-HA/BF membrane were investigated by Fourier Transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), contact angle, electromechanical universal tester, in vitro soaking in simulated body fluid (SBF) and in vitro cell cultureexperiment. The results demonstrated that the n-HA dispersity in BF matix was not affected by the prepartion condition, however, the morphologies of membrane was determined by the different preparation conditions owing to different hydrogen bond shrinkage. Moreover, the hydrophilicity of the composite membrane was improved under the condition of the membrane formation in oven, freeze drying and high addition content of n-HA, and the mechanical properties of composite membrane depended on n-HA content. In vitro soaking behavior indicated that the degradability and bone-like apatite deposition could be controled by differentpreparation conditions. And the cell proliferation experiment showed that the n-HA/BF composite membranes obtained under different preparation conditions were all non-toxic. The above results indicated that the n-HA/BF composite membrane could be obtained by a simple casting technique, and the properties could be controlled by adopting different preparation conditions, which would have a great promising as guide bone tissue regeneration (GBR) membrane, and the study would provide a new application for BF in biomedical field.

The Effect of Electrospun Dihydroartemisinin-Loaded Polycaprolactone/Collagen Scaffolds On Osteoblastic Differentiation of Human Adipose-Derived Stem Cells

In this study, Dihydroartemisinin (DHART)-loaded polycaprolactone collagen nanofibers (PCL/Col NFs) were constructed as effective biocompatible scaffolds through adjusting the proportions of hydrophobic/ hydrophilic polymers for enhanced osteoblastic differentiation of human adipose-derived stem cells (hADSCs). The designed NFs were characterized through FTIR, XRD, TGA, FE-SEM, and tensile testing. DHART-loaded PCL/Col electrospun NFs provide an ideal solution, with the potential of sustained drug release as well as inhibition of drug re-crystallization. Interestingly, inhibiting DHART re-crystallization can improve its bioavailability, providing a more effective therapeutic efficacy. Besides, the data set found through FE-SEM, MTT, PicoGreen, qPCR, and alkaline phosphatase (ALP) assays revealed the improved adhesion and proliferation rate of hADSCs cultured on PCL/Col/DHART (5%) NFs after 14 and 21 days of incubation. These findings confirmed the potential of the designed NF scaffolds for sustained/controlled release of DHART therapeutic molecules toward bone tissue regeneration and engineering.

Made by cells for cells – extracellular vesicles as next-generation mainstream medicines

ABSTRACT Current medicine has only taken us so far in reducing disease and tissue damage. Extracellular vesicles (EVs), which are membranous nanostructures produced naturally by cells, have been hailed as a next-generation medicine. EVs deliver various biomolecules, including proteins, lipids and nucleic acids, which can influence the behaviour of specific target cells. Since EVs not only mirror composition of their parent cells but also modify the recipient cells, they can be used in three key areas of medicine: regenerative medicine, disease detection and drug delivery. In this Review, we discuss the transformational and translational progress witnessed in EV-based medicine to date, focusing on two key elements: the mechanisms by which EVs aid tissue repair (for example, skin and bone tissue regeneration) and the potential of EVs to detect diseases at an early stage with high sensitivity and specificity (for example, detection of glioblastoma). Furthermore, we describe the progress and results of clinical trials of EVs and demonstrate the benefits of EVs when compared with traditional medicine, including cell therapy in regenerative medicine and solid biopsy in disease detection. Finally, we present the challenges, opportunities and regulatory framework confronting the clinical application of EV-based products.

Fibrous Polymer-Based Composites Obtained by Electrospinning for Bone Tissue Engineering

Currently, the significantly developing fields of tissue engineering related to the fabrication of polymer-based materials that possess microenvironments suitable to provide cell attachment and promote cell differentiation and proliferation involve various materials and approaches. Biomimicking approach in tissue engineering is aimed at the development of a highly biocompatible and bioactive material that would most accurately imitate the structural features of the native extracellular matrix consisting of specially arranged fibrous constructions. For this reason, the present research is devoted to the discussion of promising fibrous materials for bone tissue regeneration obtained by electrospinning techniques. In this brief review, we focus on the recently presented natural and synthetic polymers, as well as their combinations with each other and with bioactive inorganic incorporations in order to form composite electrospun scaffolds. The application of several electrospinning techniques in relation to a number of polymers is touched upon. Additionally, the efficiency of nanofibrous composite materials intended for use in bone tissue engineering is discussed based on biological activity and physiochemical characteristics.

Investigations on the Influence of Collagen Type on Physicochemical Properties of PVP/PVA Composites Enriched with Hydroxyapatite Developed for Biomedical Applications

Nowadays, a great attention is directed into development of innovative multifunctional composites which may support bone tissue regeneration. This may be achieved by combining collagen and hydroxyapatite showing bioactivity, osteoconductivity and osteoinductivity with such biocompatible polymers as polyvinylpyrrolidone (PVP) and poly(vinyl alcohol) (PVA). Here PVA/PVP-based composites modified with hydroxyapatite (HAp, 10 wt.%) and collagen (30 wt.%) were obtained via UV radiation while two types of collagen were used (fish and bovine) and crosslinking agents differing in the average molecular weight. Next, their chemical structure was characterized using Fourier transform infrared (FT-IR) spectroscopy, roughness of their surfaces was determined using a stylus contact profilometer while their wettability was evaluated by a sessile drop method followed by the measurements of their surface free energy. Subsequently, swelling properties of composites were verified in simulated physiological liquids as well as the behavior of composites in these liquids by pH measurements. It was proved that collagen-modified composites showed higher swelling ability (even 25% more) compared to unmodified ones, surface roughness, biocompatibility towards simulated physiological liquids and hydrophilicity (contact angles lower than 90°). Considering physicochemical properties of developed materials and a possibility of the preparation of their various shapes and sizes, it may be concluded that developed materials showed great application potential for biomedical use, e.g., as materials filling bone defects supporting their treatments and promoting bone tissue regeneration due to the presence of hydroxyapatite with osteoinductive and osteoconductive properties.

3D Printed SiOC(N) Ceramic Scaffolds for Bone Tissue Regeneration: Improved Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells

Bone tissue engineering has developed significantly in recent years as there has been increasing demand for bone substitutes due to trauma, cancer, arthritis, and infections. The scaffolds for bone regeneration need to be mechanically stable and have a 3D architecture with interconnected pores. With the advances in additive manufacturing technology, these requirements can be fulfilled by 3D printing scaffolds with controlled geometry and porosity using a low-cost multistep process. The scaffolds, however, must also be bioactive to promote the environment for the cells to regenerate into bone tissue. To determine if a low-cost 3D printing method for bespoke SiOC(N) porous structures can regenerate bone, these structures were tested for osteointegration potential by using human mesenchymal stem cells (hMSCs). This includes checking the general biocompatibilities under the osteogenic differentiation environment (cell proliferation and metabolism). Moreover, cell morphology was observed by confocal microscopy, and gene expressions on typical osteogenic markers at different stages for bone formation were determined by real-time PCR. The results of the study showed the pore size of the scaffolds had a significant impact on differentiation. A certain range of pore size could stimulate osteogenic differentiation, thus promoting bone regrowth and regeneration.

The Development Tendency of 3D-Printed Bioceramic Scaffolds for Applications Ranging From Bone Tissue Regeneration to Bone Tumor Therapy

Three-dimensional (3D) printing concept has been successfully employed in regenerative medicine to achieve individualized therapy due to its benefit of a rapid, accurate, and predictable production process. Traditional biocomposites scaffolds (SCF) are primarily utilised for bone tissue engineering; nevertheless, over the last few years, there has already been a dramatic shift in the applications of bioceramic (BCR) SCF. As a direct consequence, this study focused on the structural, degeneration, permeation, and physiological activity of 3D-printed BCR (3DP-B) SCF with various conformations and work systems (macros, micros, and nanos ranges), as well as their impacts on the mechanical, degeneration, porosity, and physiological activities. In addition, 3DP-B SCF are highlighted in this study for potential uses applied from bone tissue engineering (BTE) to bone tumor treatment. The study focused on significant advances in practical 3DP-B SCF that can be utilized for tumor treatment as well as bone tissue regeneration (BTR). Given the difficulties in treating bone tumors, these operational BCR SCF offer a lot of promise in mending bone defects caused by surgery and killing any remaining tumor cells to accomplish bone tumor treatment. Furthermore, a quick assessment of future developments in this subject was presented. The study not only summarizes recent advances in BCR engineering, but it also proposes a new therapeutic strategy focused on the extension of conventional ceramics’ multifunction to a particular diagnosis.