Hydrogels as Scaffolds in Bone-Related Tissue Engineering and Regeneration

Several years have passed since the medical and scientific communities leaned toward tissue engineering as the most promising field to aid bone diseases and defects resulting from degenerative conditions or trauma. Owing to their histocompatibility and non-immunogenicity, bone grafts, precisely autografts, have long been the gold standard in bone tissue therapies. However, due to issues associated with grafting, especially the surgical risks and soaring prices of the procedures, alternatives are being extensively sought and researched. Fibrous and non-fibrous materials, synthetic substitutes, or cell-based products are just a few examples of research directions explored as potential solutions. A very promising subgroup of these replacements involves hydrogels. Biomaterials resembling the bone extracellular matrix and therefore acting as 3D scaffolds, providing the appropriate mechanical support and basis for cell growth and tissue regeneration. Additional possibility of using various stimuli in the form of growth factors, cells, etc., within the hydrogel structure, extends their use as bioactive agent delivery platforms and acts in favor of their further directed development. The aim of this review is to bring the reader closer to the fascinating subject of hydrogel scaffolds and present the potential of these materials, applied in bone and cartilage tissue engineering and regeneration.     

Biomineralized polymer matrix composites for bone tissue repair: a review

Bone defects caused by trauma, infection or bone tumor resection, are highly prevalent. A small number(5%–10%) of these injuries fail to heal due to non-union and require surgical intervention. Currently, the principal treatment options for these defects are autografts, allografts, xenografts or synthetic grafts. The main problems associated with these therapies include pain,infection and donor site morbidity. Bone tissue engineering is a diverse field that focuses on the regeneration of bone by combining cells, scaffolds, growth factors and dynamic forces. There have been many recent studies utilizing biomineralized polymer matrix composites which mimic the natural structure of bone. The principal focus of this review is on recent advances in the synthesis of various types of biomineralized polymer matrix composite. Examples of the biomineralization of naturallyderived and synthetic polymers widely used for bone engineering are also summarized.     

Medical applications of organic-inorganic hybrid materials within the field of silica-based bioceramics

Research on bioceramics has evolved from the use of inert materials for mere substitution of living tissues towards the development of third-generation bioceramics aimed at inducing bone tissue regeneration. Within this context hybrid bioceramics have remarkable features resulting from the synergistic combination of both inorganic and organic components that make them suitable for a wide range of medical applications. Certain bioceramics, such as ordered mesoporous silicas, can exhibit different kind of interaction with organic molecules to develop different functions. The weak interaction of these host matrixes with drug molecules confined in the mesoporous channels allows these hybrid systems to be used as controlled delivery devices. Moreover, mesoporous silicas can be used to fabricate three (3D)-dimensional scaffolds for bone tissue engineering. In this last case, different osteoinductive agents (peptides, hormones and growth factors) can be strongly grafted to the bioceramic matrix to act as attracting signals for bone cells to promote bone regeneration process. Finally, recent research examples of organic-inorganic hybrid bioceramics, such as stimuli-responsive drug delivery systems and nanosystems for targeting of cancer cells and gene transfection, are also tackled in this tutorial review (64 references).     

Progress in Articular Cartilage Tissue Engineering: A Review on Therapeutic Cells and Macromolecular Scaffolds

Repair and regeneration of articular cartilage lesions have always been a major challenge in the medical field due to its peculiar structure (e.g., sparsely distributed chondrocytes, no blood supply, no nerves). Articular cartilage tissue engineering is considered as one promising strategy to achieve reconstruction of cartilage. With this perspective, the articular cartilage tissue engineering has been widely studied. Here, the recent progress of articular cartilage tissue engineering is reviewed. The ad hoc therapeutic cells and growth factors for cartilage regeneration are summarized and discussed. Various types of bio/macromolecular scaffolds together with their pros and cons are also reviewed and elaborated.     

生物材料表面性能调控骨髓间充质干细胞分化

结合细胞和生物可降解支架的组织工程和再生医学技术为组织、器官的修复和再生提供了一种新途径。骨髓间充质干细胞(BMSCs)具有多向分化潜能,因其取材简单、来源广泛、增殖能力强,无伦理争议,免疫排斥反应小而备受关注。BMSCs在特定区域定向分化成为靶细胞是干细胞治疗的一个重要前提,尤其受到生物材料表面正负电荷、亲疏水和不同的拓扑结构的影响。材料表面涂层蛋白或接枝多肽能够促进BMSCs的分化能力,而生物材料不同的机械性能、几何形状也会影响BMSCs的分化方向。本文综述了近期生物材料调控BMSCs分化的研究结果,为基于BMSCs的组织工程和再生医学材料的设计提供借鉴和指导。     

In situ tissue regeneration through host stem cell recruitment

The field of tissue engineering has made steady progress in translating various tissue applications. Although the classical tissue engineering strategy, which involves the use of culture-expanded cells and scaffolds to produce a tissue construct for implantation, has been validated, this approach involves extensive cell expansion steps, requiring a lot of time and laborious effort before implantation. To bypass this ex vivo process, a new approach has been introduced. In situ tissue regeneration utilizes the body''s own regenerating capacity by mobilizing host endogenous stem cells or tissue-specific progenitor cells to the site of injury. This approach relies on development of a target-specific biomaterial scaffolding system that can effectively control the host microenvironment and mobilize host stem/progenitor cells to target tissues. An appropriate microenvironment provided by implanted scaffolds would facilitate recruitment of host cells that can be guided to regenerating structural and functional tissues.     

Ordered mesoporous materials in the context of drug delivery systems and bone tissue engineering

Chemistry, materials science and medicine are research areas that converge in the field of drug delivery systems and tissue engineering. This paper tries to introduce an example of such an interaction, aimed at solving health issues within the world of biomaterials. Ordered mesoporous materials can be loaded with different organic molecules that would be released afterwards, in a controlled fashion, inside a living body. These materials can also react with the body fluids giving rise to carbonated nanoapatite particles as the products of such a chemical interaction; these particles, equivalent to biological apatites, enable the regeneration of bone tissue.     

Smart Porous Multi-Stimulus Polysaccharide-Based Biomaterials for Tissue Engineering

Recently, tissue engineering and regenerative medicine studies have evaluated smart biomaterials as implantable scaffolds and their interaction with cells for biomedical applications. Porous materials have been used in tissue engineering as synthetic extracellular matrices, promoting the attachment and migration of host cells to induce the in vitro regeneration of different tissues. Biomimetic 3D scaffold systems allow control over biophysical and biochemical cues, modulating the extracellular environment through mechanical, electrical, and biochemical stimulation of cells, driving their molecular reprogramming. In this review, first we outline the main advantages of using polysaccharides as raw materials for porous scaffolds, as well as the most common processing pathways to obtain the adequate textural properties, allowing the integration and attachment of cells. The second approach focuses on the tunable characteristics of the synthetic matrix, emphasizing the effect of their mechanical properties and the modification with conducting polymers in the cell response. The use and influence of polysaccharide-based porous materials as drug delivery systems for biochemical stimulation of cells is also described. Overall, engineered biomaterials are proposed as an effective strategy to improve in vitro tissue regeneration and future research directions of modified polysaccharide-based materials in the biomedical field are suggested.     

Synthesising injectable molecular self-curing polymer from monomer derived from lignocellulosic oil palm empty fruit bunch biomass: A review on treating Osteoarthritis

Osteoarthritis (OA) is a chronic and irreversible degenerative joint disease that most commonly affects individuals in their forties and fifties worldwide due to the continuously increasing life expectancy. Although joint replacement is an effective remedy for severe end-stage OA, the functional outcomes could be unsatisfactory, while the implants might have a limited lifespan. Due to the drawbacks and limitations of the joint replacement approach, bone Tissue Engineering (TE) is one of the promising bone tissue regeneration technologies that aid in cartilage repair and regeneration and has attracted the attention of experts. The advanced development of biopolymers, in particular biopolymer derived from Oil Palm Empty Fruit Bunch (OPEFB), has been utilised in the fabrication of scaffolds that serve as a crucial component in bone TE. The abundant supply of OPEFB biomass and the increasing trend of converting waste into wealth for environmental sustainability have also provided the opportunity and interest to fully apply biopolymer-derived materials for bone scaffolding and other applications. Therefore, this paper aimed to provide a review of the biopolymers derived from OPEFB for the treatment of OA and other related applications. A brief overview of the biomass sources in Malaysia was presented, followed by a discussion on the chemical compositions and pre-treatment methods of OPEFB by using organosolv pre-treatment and enzymatic hydrolysis for maximum glucose recovery, monomer derived from cellulose OPEFB and synthesizing self-curing polymer scaffold. Additionally, a detailed review of the polymeric biomaterials in bone TE for the fabrication of scaffolds were included in this review. Most importantly, the paper described the potential use of injectable polymeric biomaterials that provide a significant benefit in orthopaedic applications. Overall, this paper provides a perspective on the potential of OPEFB-derived injectable scaffolds as an alternative OA treatment and future bone TE applications.     

电活性导电聚合物在生物医学中的应用

以聚吡咯、聚噻吩和聚苯胺为代表的电活性导电聚合物(electroactive conducting polymers,ECP)已成为生物材料、组织工程及临床医学领域关注的焦点.目前研究主要集中在生物相容性、细胞及组织工程、蛋白质分离、DNA吸附修复、可控药物释放、生物传感器、神经探针等方面.ECP在神经细胞、脑细胞、心肌干细胞再生和功能调节,定向诱导组织器官的再生修复方面具有潜在的应用前景.本文主要综述了聚吡咯(PPy)和聚苯胺(PANi)在生物医学领域的研究进展,和电刺激对细胞生长和干细胞分化的影响,并建议了一些前景可观的相关研究方向.     

Bacterial Nanocellulose in Dentistry: Perspectives and Challenges

Bacterial cellulose (BC) is a natural polymer that has fascinating attributes, such as biocompatibility, low cost, and ease of processing, being considered a very interesting biomaterial due to its options for moldability and combination. Thus, BC-based compounds (for example, BC/collagen, BC/gelatin, BC/fibroin, BC/chitosan, etc.) have improved properties and/or functionality, allowing for various biomedical applications, such as artificial blood vessels and microvessels, artificial skin, and wounds dressing among others. Despite the wide applicability in biomedicine and tissue engineering, there is a lack of updated scientific reports on applications related to dentistry, since BC has great potential for this. It has been used mainly in the regeneration of periodontal tissue, surgical dressings, intraoral wounds, and also in the regeneration of pulp tissue. This review describes the properties and advantages of some BC studies focused on dental and oral applications, including the design of implants, scaffolds, and wound-dressing materials, as well as carriers for drug delivery in dentistry. Aligned to the current trends and biotechnology evolutions, BC-based nanocomposites offer a great field to be explored and other novel features can be expected in relation to oral and bone tissue repair in the near future.     

Clinical Application of Resorbable Polymers in Guided Bone Regeneration

Summary : Guided bone regeneration was shown to be successful in vitro and in vivo using resorbable or nonresorbable materials. Resorbable material has the advantage of progressive substitution by bone. Resorbable polymers of ∝-hydroxy acids like polylactide or polyglycolide are commonly used for tissue engineering and in guided bone regeneration. In clinical studies, guided bone regeneration was successful in non-weight bearing bone, e.g. in dental surgery and craniofacial surgery. This paper reports the preliminary result of using resorbable poly(L/DL-lactide) 80/20% scaffolds in weight bearing bone with infected large segmental defects as well as in small bony defects of hand due to benign tumour, bone graft donor sites and as an adjunct for joint fusion. Resorbable polylactide implants were used in the form of membranes, large 3-D sponges, chips or as injectable paste. Implants were impregnated with marrow blood to add an osteoinductive component. Long-term follow up revealed that these implants are promising candidates for bone graft substitutes.     

Synthesis and applications of graphene oxide aerogels in bone tissue regeneration: a review

Development of biocompatible porous supports is a promising strategy in the field of tissue engineering for the repair and regeneration of bone tissues with severe damage. Graphene oxide aerogels (GOAs) are excellent candidates for the manufacture of these systems due to their porosity, ability to imitate bone structure, and mechanical resistance, and according to their surface chemical reactivity, they can facilitate osseointegration, osteogenesis, osteoinduction and osteoconduction. In this review, synthesis of GOAs from the most primary source is described, and recent studies on the use of these functionalized carbonaceous foams as scaffolding for bone tissue regeneration are presented.     

Enhanced Bone Defect Repair by Polymeric Substitute Fillers of MultiArm Polyethylene Glycol‐Crosslinked Hyaluronic Acid Hydrogels

Bone regeneration is still one of the greatest challenges for the treatment of bone defects since no current clinical approach has been proven effective. To develop an alternative biodegradable bone graft material, multiarm polyethylene glycol (PEG) crosslinked hyaluronic acid (HA) hydrogels are synthesized and applied to promote osteogenesis of mesenchymal stem cells (MSCs) with the ultimate goal for bone defect repair. The multiarm PEG‐HA hydrogels provide a significant improvement of alkaline phosphatase (ALP) activity and calcium mineralization of the in vitro encapsulated MSCs under osteogenic condition after 3, 7, and 28 days. In addition, the multiarm PEG‐HA hydrogels also facilitate healing of the cranial bone defects more effectively in a Sprague Dawley rat model after 10 weeks of implantation based on histological evaluations and microcomputed tomography analysis. These promising results set the stage for the development of innovative biodegradable hydrogels to provide a more effective and versatile treatment option for bone regeneration.     

Silk Fibroin Combined with Electrospinning as a Promising Strategy for Tissue Regeneration

The development of tissue engineering scaffolds is of great significance for the repair and regeneration of damaged tissues and organs. Silk fibroin (SF) is a natural protein polymer with good biocompatibility, biodegradability, excellent physical and mechanical properties and processability, making it an ideal universal tissue engineering scaffold material. Nanofibers prepared by electrospinning have attracted extensive attention in the field of tissue engineering due to their excellent mechanical properties, high specific surface area, and similar morphology as to extracellular matrix (ECM). The combination of silk fibroin and electrospinning is a promising strategy for the preparation of tissue engineering scaffolds. In this review, the research progress of electrospun silk fibroin nanofibers in the regeneration of skin, vascular, bone, neural, tendons, cardiac, periodontal, ocular and other tissues is discussed in detail.     

Xylan hemicellulose improves chitosan hydrogel for bone tissue regeneration

The hemicellulose xylan, which has immunomodulatory effects, has been combined with chitosan to form a composite hydrogel to improve the healing of bone fractures. This thermally responsive and injectable hydrogel, which is liquid at room temperature and gels at physiological temperature, improves the response of animal host tissue compared with similar pure chitosan hydrogels in tissue engineering models. The composite hydrogel was placed in a subcutaneous model where the composite hydrogel is replaced by host tissue within 1 week, much earlier than chitosan hydrogels. A tibia fracture model in mice showed that the composite encourages major remodeling of the fracture callus in less than 4 weeks. A non‐union fracture model in rat femurs was used to demonstrate that the composite hydrogel allows bone regeneration and healing of defects that with no treatment are unhealed after 6 weeks. These results suggest that the xylan/chitosan composite hydrogel is a suitable bone graft substitute able to aid in the repair of large bone defects. Copyright © 2016 John Wiley & Sons, Ltd.     

An Effective Osteogenesis Porous CaP/Collagen Interface Compatible with Various Substrates Fabricated by Controlled Mineralization in a Delicately Adjustable Organic Matrix

Increasing bone formation on the surfaces of implants such as screws, plates, or shims holds great significance for clinical medicine. However, osteogenesis implant coatings that mimic natural bone in terms of both their components and structural features are still lacking. Here we report the biomimetic interface of calcium phosphate (CaP) in a collagen matrix fabricated by controlled mineralization that presents biomimetic porous features. The porous CaP/collagen interface, with a thickness of about 1 μm, significantly enhances osteogenesis, as verified at both the gene and protein levels as well as by in vivo experiments. Taking advantage of the generality of the method, the biomimetic interface was prepared on a variety of substrates, including conductive substrates, 3D metal meshes, plastic or elastic substrates, and even on filter papers. The adjustability and generality of the method have enabled new characterization tests to be developed during experiments on cells and thus should greatly facilitate clinical medicine and tissue engineering.     

Tofu as excellent scaffolds for potential bone regeneration

Biomimetic scaffolds present the promising potential for bone regeneration. As a natural gel-like traditional food, tofu with porous architecture and proved biological safety indicated a good potential to be a natural scaffold and easy to be improved by surface modification. Hereon, we fabricated the tofu-based scaffolds and systematically explored the potential for bone tissue engineering. In addition, the collagen has been introduced by simple coating to further enhance the surface compatibility of the tofu-based scaffold in bone regeneration. The results showed that the tofu-based scaffolds possessed good porous structure and cytocompatibility. Notably, the tofu-based scaffolds could improve the expression of osteogenesis-related genes and proteins, leading to better bone regeneration after 2 months of implantation. All the results indicated that tofu would become an outstanding sustainable natural porous scaffold for bone regeneration with excellent bioactivities.     

Tofu as excellent scaffolds for potential bone regeneration

Biomimetic scaffolds present the promising potential for bone regeneration. As a natural gel-like traditional food, tofu with porous architecture and proved biological safety indicated a good potential to be a natural scaffold and easy to be improved by surface modification. Hereon, we fabricated the tofubased scaffolds and systematically explored the potential for bone tissue engineering. In addition, the collagen has been introduced by simple coating to further enhance the surface compatibility of the tofubased scaffold in bone regeneration. The results showed that the tofu-based scaffolds possessed good porous structure and cytocompatibility. Notably, the tofu-based scaffolds could improve the expression of osteogenesis-related genes and proteins, leading to better bone regeneration after 2 months of implantation. All the results indicated that tofu would become an outstanding sustainable natural porous scaffold for bone regeneration with excellent bioactivities.     

Oxygen‐Sensing Methods in Biomedicine from the Macroscale to the Microscale

Oxygen monitoring has been a topic of exhaustive study given its central role in the biochemistry of life. The ability to quantify the physiological distribution and real‐time dynamics of oxygen from sub‐cellular to macroscopic levels is required to fully understand the mechanisms associated with both normal physiology and disease states. This Review will present the most significant recent advances in the development of oxygen‐sensing materials and techniques, including polarographic, nuclear medicine, magnetic resonance, and optical approaches, that can be applied specifically for the real‐time monitoring of oxygen dynamics in cellular and tissue environments. As some of the most exciting recent advances in synthetic methods and biomedical applications have been in the field of optical oxygen sensors, a major focus will be on the development of these toolkits.