Bone tissue engineering, scaffold requirements and the utilization of natural polymers

Bone and cartilage injury is common, tissue engineered scaffolds are potential means to repair. Because most of the scaffold materials used in bone and cartilage tissue engineering are bio-inert, it is necessary to increase the cellular adhesion ability of during tissue engineering reconstruction. The Arginine - Glycine - Aspartic acid (Arg-Gly-Asp, RGD) peptide family is considered as a specific recognition site for the integrin receptors. Integrin receptors are key regulators of cell-cell and cell-extracellular microenvironment communication. Therefore, the RGD polypeptide families are considered as suitable candidates for treatment of a variety of diseases and for the regeneration of various tissues and organs. Many scaffold material for tissue engineering and has been approved by US Food and Drug Administration (FDA) for human using. The application of RGD peptides in bone and cartilage tissue engineering was reported seldom. Only a few reviews have summarized the applications of RGD peptide with alloy, bone cements, and PCL in bone tissue engineering. Herein, we summarize the application progress of RGD in bone and cartilage tissue engineering, discuss the effects of structure, sequence, concentration, mechanical stimulation, physicochemical stimulation, and time stimulation of RGD peptide on cells differentiation, and introduce the mechanism of RGD peptide through integrin in the field of bone and cartilage tissue engineering.

Tissue engineering is based on combining cells with suitable scaffolds and growth factors. Recently, bone tissue engineering has been especially investigated deeply due to a large number of bone-related diseases. One approach to improve scaffolds is based on using piezoelectric materials as a way to influence the growing bone tissue by mechanical stress. Another method to stimulate tissue growth is by applying an external magnetic field to composites of magnetostrictive and piezoelectric materials, as well as the possibility to prepare oriented surfaces by orienting embedded magnetic fibers or nanoparticles. In addition, magnetic scaffolds without other special properties have also been reported to show improved properties for bone tissue and other tissue engineering. Here, we provide an overview of recent research on magnetic scaffolds for tissue engineering, differentiating between bone and other tissue engineering. We show the advantages of magnetic scaffolds, especially related to cell guidance and differentiation, and report recent progress in the production and application of such magnetic substrates for different areas of tissue engineering.

11 - Bioactive glass composites for bone and musculoskeletal tissue engineering

Bone tissue engineering is a promising approach that uses seed-cell-scaffold drug delivery systems to reconstruct bone defects caused by trauma, tumors, or other diseases (e.g., periodontitis). Metformin, a widely used medication for type II diabetes, has the ability to enhance osteogenesis and angiogenesis by promoting cell migration and differentiation. Metformin promotes osteogenic differentiation, mineralization, and bone defect regeneration via activation of the AMP-activated kinase (AMPK) signaling pathway. Bone tissue engineering depends highly on vascular networks for adequate oxygen and nutrition supply. Metformin also enhances vascular differentiation via the AMPK/mechanistic target of the rapamycin kinase (mTOR)/NLR family pyrin domain containing the 3 (NLRP3) inflammasome signaling axis. This is the first review article on the effects of metformin on stem cells and bone tissue engineering. In this paper, we review the cutting-edge research on the effects of metformin on bone tissue engineering. This includes metformin delivery via tissue engineering scaffolds, metformin-induced enhancement of various types of stem cells, and metformin-induced promotion of osteogenesis, angiogenesis, and its regulatory pathways. In addition, the dental, craniofacial, and orthopedic applications of metformin in bone repair and regeneration are also discussed.

Bone tissue engineering (BTE) applications and regenerative strategies have been used to improve the clinical practice of repairing large bone defects associated with surgical resections, congenital malformations, and trauma. The scaffolds are designed to stimulate a biological response, including cell interactions, and guide tissue regeneration by functioning as artificial biomimetic extracellular matrixes. Polymeric biomaterials are suitable for bone tissue engineering since they possess both chemical and physical properties, enabling the control of shape, morphology, and biodegradability, which makes them suitable for bone regeneration and tissue engineering applications. In vivo animal models were studied for collagen, chitosan, poly (lactic acid) (PLA) and high density polyethylene (HDPE), the four most common polymers employed in bone tissue engineering. Through analysis of the results of this review, the in vivo studies can provide a large-scale evaluation of the possibility of achieving optimal bone-forming capabilities and regenerative capabilities. Furthermore, the review will serve as an essential reference for bone tissue engineering applications as well as contribute to the development of novel in vivo investigations

Three-dimensional porous scaffolds play an important role in cartilage and bone tissue engineering as temporary templates for transplanted cells to control their adhesion and proliferation to guide the formation of the new tissues. The scaffolds should be biodegradable, biocompatible, mechanically strong, and capable of being formed into desired shapes. Biodegradable synthetic polymers and naturally derived collagen have their respective advantages and drawbacks. Hybridization of the two kinds of polymers has been carried out to combine their respective advantages. This review will summarize some of the recently developed porous scaffolds having hybrid, biphasic and leakproof structures, and their application to bone and cartilage tissue engineering.

The repair and regeneration of critical-sized bone defects remain an urgent challenge. Bone tissue engineering represents an exciting solution for regeneration of large bone defects. Recently, the importance of innervation in tissue-engineered bone regeneration has been increasingly recognized. The cross talk between nerve and bone provides important clues for bone repair and regeneration. Furthermore, the promotion of angiogenesis by innervation can accelerate new bone formation. However, the mechanisms involved in the promotion of vascular and bone regeneration by the nervous system have not yet been established. In addition, simultaneous neurogenesis and vascularization in bone tissue engineering have not been fully investigated. This article represents the first review on the effects of innervation in enhancing angiogenesis and osteogenesis in bone and dental tissue engineering. Cutting-edge research on the effects of innervation through biomaterials on bone and dental tissue repairs is reviewed. The effects of various nerve-related factors and cells on bone regeneration are discussed. Finally, novel clinical applications of innervation for bone, dental, and craniofacial tissue regeneration are also examined.

Biomaterials for Regenerative Medicine

Bone tissue engineering is a pillar of regenerative medicine; traditional bone autografts, allografts, and metallic implants face difficulties due to donor site morbidity, risks of infection, and poor integration with the host bone. Nanohydroxyapatite (nHA) has become a popular synthetic tissue-engineered approach, although its brittleness and low fracture toughness limit its applications. This systematic review explores nHA-bioactive glass composites (HAGNs) as promising solutions for bone regeneration, analyzing their biocompatibility, osteoconductivity, and mechanical properties. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search strategy was employed across multiple databases from January 2000 to February 2024, using MeSH terms related to hydroxyapatite (HA), glass nanoparticles, and bone regeneration. Eligible studies included peer-reviewed articles reporting outcomes relevant to bone healing or tissue engineering using HA glass nanoparticles. The search yielded 57 records, with 15 studies meeting the inclusion criteria after screening and selection. These studies explored various fabrication methods and consolidation techniques for nHA-based scaffolds, highlighting their improved biocompatibility, osteoconductivity, and potential for bone regeneration. Limitations involved long drying periods, the need for specific consolidation conditions, and more studies to confirm long-term performance. Findings underscored the importance of preserving key properties of nHA, such as low crystallinity and nanoscale dimensions, to mimic natural bone tissue effectively. nHA and bioactive glass composites show significant potential in bone tissue engineering. They offer the combination of biocompatibility, osteoconductivity, and mechanical strength necessary for effective bone regeneration. Further research is needed to facilitate the clinical translation of these biomaterials.

Bone Tissue Grafting and Tissue Engineering Concepts

Bone Tissue Grafting and Tissue Engineering Concepts

Despite current medicine's fast-paced advances, many acute and chronic illnesses still lack truly effective and safe therapies. Cancer treatments often lead to off-target healthy tissue damage and poor therapeutic outcomes, wound standard treatments generally demonstrate poor healing efficacy and increased susceptibility to infection, and bone tissue engineering and myocardial tissue engineering can result in immunological rejection and limited availability. To tackle these issues, injectable hydrogels have emerged, and through the incorporation of nanoparticles, nanocomposite hydrogels have appeared as versatile platforms, offering improved biocompatibility, mechanical strength, stability, and precise controlled drug release, as well as targeted delivery with increased drug retention at the site of action, reducing systemic drug distribution to non-target sites. With the ability to deliver a diverse range of therapeutic entities, including low molecular weight drugs, proteins, antibodies, and even isolated cells, injectable nanocomposite hydrogels have revolutionized current therapies, working as multifunctional platforms capable of improving efficacy and safety in cancer treatment, including in chemotherapy, immunotherapy, photothermal therapy, magnetic hyperthermia, photodynamic therapy, chemodynamic therapy, radiotherapy, molecularly targeted therapy, and after tumor surgical removal, and in general, chronic diabetic or tumor-induced wound healing, as well as in bone tissue engineering and myocardial tissue engineering. This review provides a thorough summary and critical insight of current advances on injectable nanocomposite hydrogels as an innovative approach that could bring substantial contributions to biomedical research and clinical practice, with a focus on their applications in cancer therapy, wound healing management, and tissue engineering.

To preserve functionality, bone is an active tissue that can constantly reconstruct itself through modeling and remodeling. It plays critical roles in the body, including maintaining mineral homeostasis, serving as the adult human body’s core site of hematopoiesis, and supporting the structures of the body’s soft tissues. It possesses the natural regeneration capacity, but large and complex lesions often require surgical intervention. Multiple omics integrate proteomics, metabolomics, genomics, and transcriptomics to provide a comprehensive understanding of biological processes like bone tissue injury and healing in bone tissue regeneration and engineering. Recently, bone tissue engineering and regenerative medicines have offered promising tools for bone regeneration using a multi-omics approach. Thus, this article will highlight the role of multiple omics in understanding bone tissue injury and healing. It will discuss the role of bone tissue engineering in developing bone substitutes that can replace translational medicine. Lastly, new developments in bone tissue engineering and regenerative medicine, along with multi-omics approaches, offer promising tools for bone regeneration.

Jellyfish collagen serves as a competitive alternative to mammalian-sourced collagen in many practical aspects. For instance, jellyfish collagen lacks religious constraints when compared to bovine or porcine sources and promises batch-to-batch consistency. Another advantage is its structural similarity with many mammalian collagen types, providing a biocompatible matrix for different cell types as "collagen type 0". This paper intends to investigate jellyfish collagen (Jellagen®) in two applications. This investigation aims to establish an initial understanding of jellyfish collagen in biotechnology. More specifically, in cell culture and the field of tissue engineering. The jellyfish collagen was comparatively tested as a coating material for multi-well plates as one of the most extensively used tools in cell culture and in the form of three-dimensional (3D) scaffolds intended for bone tissue engineering (BTE) applications. Both, the coated well plates and the scaffolds were seeded with fibroblasts and pre-osteoblasts, separately. In vitro cytocompatibility assays in accordance with EN ISO 10993-5/-12 regulations and LIVE-DEAD-stainings were carried out to study the cell viability, cytotoxicity and proliferation of these two cell lines. The results showed that collagen extracted from R. pulmo jellyfish can be an alternative to mammalian-derived collagen. Fibroblasts showed comparable cell viability to the medium control and an increased cell proliferation on the well plates indicating that these coated well plates can be used in cell culture, particularly in biocompatibility studies of biomaterials (as fibroblasts are used in this respective field extensively). The viability of pre-osteoblasts significantly exceeded the medium control in case of the jellyfish 3D scaffolds. These cells exhibited favorable healthy behavior on this marine collagen, suggesting that Jellagen® collagen can be used in studies of (bone) tissue regeneration and especially as scaffolds in BTE. In conclusion, jellyfish collagen provides biocompatibility and adhesive properties for both cell culture and BTE applications.

Roughly 1.71 billion people worldwide suffer from large bone abnormalities, which are the primary cause of disability. Traditional bone grafting procedures have several drawbacks that impair their therapeutic efficacy and restrict their use in clinical settings. A great deal of work has been done to create fresh, more potent strategies. Under these circumstances, a crucial technique for the regeneration of major lesions has emerged: bone tissue engineering (BTE). BTE involves the use of biomaterials that can imitate the natural design of bone. To yet, no biological material has been able to fully meet the parameters of the perfect implantable material, even though several varieties have been created and investigated for bone regeneration. Against this backdrop, researchers have focused a great deal of interest over the past few years on the subject of nanotechnology and the use of nanostructures in regenerative medicine. The ability to create nanoengineered particles that can overcome the current constraints in regenerative strategies─such as decreased cell proliferation and differentiation, insufficient mechanical strength in biological materials, and insufficient production of extrinsic factors required for effective osteogenesis has revolutionized the field of bone and tissue engineering. The effects of nanoparticles on cell characteristics and the application of biological materials for bone regeneration are the main topics of our review, which summarizes the most recent in vitro and in vivo research on the application of nanotechnology in the context of BTE.