Biomaterials Translational最新文献

Stem cells have been one of the ideal sources for tissue regeneration owing to their capability of self-renewal and differentiation. In vivo, the extracellular microenvironment plays a vital role in modulating stem cell fate. When developing biomaterials for regenerative medicine, incorporating biochemical and biophysical cues to mimic extracellular matrix can enhance stem cell lineage differentiation. More specifically, modulating the stem cell fate can be achieved by controlling the nanotopographic features on synthetic surfaces. Optimization of nanotopographical features leads to desirable stem cell functions, which can maximize the effectiveness of regenerative treatment. In this review, nanotopographical surfaces, including static patterned surface, dynamic patterned surface, and roughness are summarized, and their fabrication, as well as the impact on stem cell behaviour, are discussed. Later, the recent progress of applying nanotopographical featured biomaterials for altering different types of stem cells is presented, which directs the design and fabrication of functional biomaterial. Last, the perspective in fundamental research and for clinical application in this field is discussed.

Based on studies over the last several decades, the self-renewing skeletal lineages derived from bone marrow stroma could be an ideal source for skeletal tissue engineering. However, the markers for osteogenic precursors; i.e., bone marrowderived skeletal stem cells (SSCs), in association with other cells of the marrow stroma (bone marrow stromal cells, BMSCs) and their heterogeneous nature both in vivo and in vitro remain to be clarified. This review aims to highlight: i) the importance of distinguishing BMSCs/SSCs from other "mesenchymal stem/stromal cells", and ii) factors that are responsible for their heterogeneity, and how these factors impact on the differentiation potential of SSCs towards bone. The prospective role of SSC enrichment, their expansion and its impact on SSC phenotype is explored. Emphasis has also been given to emerging single cell RNA sequencing approaches in scrutinizing the unique population of SSCs within the BMSC population, along with their committed progeny. Understanding the factors involved in heterogeneity may help researchers to improvise their strategies to isolate, characterize and adopt best culture practices and source identification to develop standard operating protocols for developing reproducible stem cells grafts. However, more scientific understanding of the molecular basis of heterogeneity is warranted that may be obtained from the robust high-throughput functional transcriptomics of single cells or clonal populations.

Microorganisms with innate and artificial advantages have been regarded as intelligent drug delivery systems for cancer therapy with the help of engineering technology. Although numerous studies have confirmed the promising prospects of microorganisms in cancer, several problems such as immunogenicity and toxicity should be addressed before further clinical applications. This review aims to investigate the development of engineered microorganism-based delivery systems for targeted cancer therapy. The main types of microorganisms such as bacteria, viruses, fungi, microalgae, and their components and characteristics are introduced in detail. Moreover, the engineering strategies and biomaterials design of microorganisms are further discussed. Most importantly, we discuss the innovative attempts and therapeutic effects of engineered microorganisms in cancer. Taken together, engineered microorganism-based delivery systems hold tremendous promise for biomedical applications in targeted cancer therapy.

Reconstruction after resection has always been an urgent problem in the treatment of bone tumours. There are many methods that can be used to reconstruct bone defects; however, there are also many complications, and it is difficult to develop a safe and effective reconstruction plan for the treatment of bone tumours. With the rapid development of digital orthopaedics, three-dimensional printing technology can solve this problem. The three-dimensional printing of personalised prostheses has many advantages. It can be used to print complex structures that are difficult to fabricate using traditional processes and overcome the problems of stress shielding and low biological activity of conventional prostheses. In this study, 12 patients with bone tumours were selected as research subjects, and based on individualised reverse-engineering design technology, a three-dimensional model of each prosthesis was designed and installed using medical image data. Ti6Al4V was used as the raw material to prepare the prostheses, which were used to repair bone defects after surgical resection. The operation time was 266.43 ± 21.08 minutes (range 180-390 minutes), and intraoperative blood loss was 857.26 ± 84.28 mL (range 800-2500 mL). One patient had delayed wound healing after surgery, but all patients survived without local tumour recurrence, and no tumour metastasis was found. No aseptic loosening or structural fracture of the prosthesis, and no non-mechanical prosthesis failure caused by infection, tumour recurrence, or progression was observed. The Musculo-Skeletal Tumour Society (MSTS) score of limb function was 22.53 ± 2.09 (range 16-26), and ten of the 12 patients scored ≥ 20 and were able to function normally. The results showed that three-dimensional printed prostheses with an individualised design can achieve satisfactory short-term clinical efficacy in the reconstruction of large bone defects after bone tumour resection.

Perivascular delivery of therapeutic agents against established aetiologies for occlusive vascular remodelling has great therapeutic potential for vein graft failure. However, none of the perivascular drug delivery systems tested experimentally have been translated into clinical practice. In this study, we established a novel strategy to locally and sustainably deliver the cyclin-dependent kinase 8/19 inhibitor Senexin A (SenA), an emerging drug candidate to treat occlusive vascular disease, using graphene oxide-hybridised hyaluronic acid-based hydrogels. We demonstrated an approach to accommodate SenA in hyaluronic acid-based hydrogels through utilising graphene oxide nanosheets allowing for non-covalent interaction with SenA. The resulting hydrogels produced sustained delivery of SenA over 21 days with tunable release kinetics. In vitro assays also demonstrated that the hydrogels were biocompatible. This novel graphene oxide-incorporated hyaluronic acid hydrogel offers an optimistic outlook as a perivascular drug delivery system for treating occlusive vascular diseases, such as vein graft failure.

Hydrogen sulfide (H₂S) has been reported as an endogenous gasotransmitter that contributes to the modulation of a myriad of biological signalling pathways, which includes maintaining homeostasis in living organisms at physiological concentrations, controlling protein sulfhydration and persulfidation for signalling processes, mediating neurodegeneration, and regulating inflammation and innate immunity, etc. As a result, researchers are actively exploring effective approaches to evaluate the properties and the distribution of H₂S in vivo. Furthermore, the regulation of the physiological conditions of H₂S in vivo introduces the opportunity to further study the molecular mechanisms by which H₂S regulates cellular functions. In recent years, many H₂S-releasing compounds and biomaterials that can deliver H₂S to various body systems have been developed to provide sustained and stable H₂S delivery. Additionally, various designs of these H₂S-releasing biomaterials have been proposed to aid in the normal conduction of physiological processes, such as cardioprotection and wound healing, by modulating different signalling pathways and cell functionalities. Using biomaterials as a platform to control the delivery of H₂S introduces the opportunity to fine tune the physiological concentration of H₂S in vivo, a key to many therapeutic applications. In this review, we highlight recent research works concerning the development and application of H₂S-releasing biomaterials with a special emphasis to different release triggering conditions in in vivo studies. We believe that the further exploration of the molecular mechanisms underlying H₂S donors and their function when incorporated with various biomaterials will potentially help us understand the pathophysiological mechanisms of different diseases and assist the development of H₂S-based therapies.

Nanotopographical features can be beneficial in augmenting cell functions and increasing osteogenic potential. However, the relationships between surface topographies and biological responses are difficult to establish due to the difficulty in controlling the surface topographical features at a low-nanometre scale. Herein, we report the fabrication of well-defined controllable titanium dioxide (TiO₂) nanotube arrays with a wide range of pore sizes, 30-175 nm in diameter, and use of the electrochemical anodization method to assess the effect of surface nanotopographies on cell morphology and adhesion. The results show that TiO₂ nanotube arrays with pore sizes of 30 and 80 nm allowed for cell spreading of bone marrow-derived mesenchymal stem cells with increased cell area coverage. Additionally, cell adhesion was significantly enhanced by controlled nanotopographies of TiO₂ nanotube arrays with 80 nm pore size. Our results demonstrate that surface modification at the nano-scale level with size tunability under controlled chemical/physical properties and culture conditions can greatly impact cell responses. These findings point to a new direction of material design for bone-tissue engineering in orthopaedic applications.

Cartilage injuries are common problems that increase with the population aging. Cartilage is an avascular tissue with a relatively low level of cellular mitotic activity, which makes it impossible to heal spontaneously. To compensate for this problem, three-dimensional bio-printing has attracted a great deal of attention in cartilage tissue engineering. This emerging technology aims to create three-dimensional functional scaffolds by accurately depositing layer-by-layer bio-inks composed of biomaterial and cells. As a novel bio-ink, a decellularized extracellular matrix can serve as an appropriate substrate that contains all the necessary biological cues for cellular interactions. Here, this review is intended to provide an overview of decellularized extracellular matrix-based bio-inks and their properties, sources, and preparation process. Following this, decellularized extracellular matrix-based bio-inks for cartilage tissue engineering are discussed, emphasizing cell behavior and in-vivo applications. Afterward, the current challenges and future outlook will be discussed to determine the conclusing remarks.

Osteoarthritis is the most common chronic degenerative joint disease, recognized by the World Health Organization as a public health problem that affects millions of people worldwide. The project Biomaterials and Additive Manufacturing: Osteochondral Scaffold (BAMOS) innovation applied to osteoarthritis, funded under the frame of the Horizon 2020 Research and Innovation Staff Exchanges (RISE) program, aims to delay or avoid the use of joint replacements by developing novel cost-effective osteochondral scaffold technology for early intervention of osteoarthritis. The multidisciplinary consortium of BAMOS, formed by international leading research centres, collaborates through research and innovation staff exchanges. The project covers all the stages of the development before the clinical trials: design of scaffolds, biomaterials development, processability under additive manufacturing, in vitro test, and in vivo test. This paper reports the translational practice adopted in the project in in vivo assessment of the osteochondral scaffolds developed.