Considering the advantages and disadvantages of biomaterials used for the production of 3D scaffolds for tissue engineering, new strategies for designing advanced functional biomimetic structures ...have been reviewed. We offer a comprehensive summary of recent trends in development of single- (metal, ceramics and polymers), composite-type and cell-laden scaffolds that in addition to mechanical support, promote simultaneous tissue growth, and deliver different molecules (growth factors, cytokines, bioactive ions, genes, drugs, antibiotics, etc.) or cells with therapeutic or facilitating regeneration effect. The paper briefly focuses on divers 3D bioprinting constructs and the challenges they face. Based on their application in hard and soft tissue engineering, in vitro and in vivo effects triggered by the structural and biological functionalized biomaterials are underlined. The authors discuss the future outlook for the development of bioactive scaffolds that could pave the way for their successful imposing in clinical therapy.
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•Recent trends in single-, composite-type and cell-laden scaffolds are discussed.•3D constructs dedicated for hard and soft tissue application are reviewed.•Scaffolds for delivering growth factors, cytokines, bioactive ions, genes, drugs, etc.•In vitro and in vivo effects triggered by the functionalized biomaterials are revealed.•Future outlook for the development of bioactive scaffolds is summarized.
Advanced therapeutic dressings that take active part in wound healing to achieve rapid and complete healing of chronic wounds is of current research interest. There is a desire for novel strategies ...to achieve expeditious wound healing because of the enormous financial burden worldwide. This paper reviews the current state of wound healing and wound management products, with emphasis on the demand for more advanced forms of wound therapy and some of the current challenges and driving forces behind this demand. The paper reviews information mainly from peer-reviewed literature and other publicly available sources such as the US FDA. A major focus is the treatment of chronic wounds including amputations, diabetic and leg ulcers, pressure sores, and surgical and traumatic wounds (e.g., accidents and burns) where patient immunity is low and the risk of infections and complications are high. The main dressings include medicated moist dressings, tissue-engineered substitutes, biomaterials-based biological dressings, biological and naturally derived dressings, medicated sutures, and various combinations of the above classes. Finally, the review briefly discusses possible prospects of advanced wound healing including some of the emerging physical approaches such as hyperbaric oxygen, negative pressure wound therapy and laser wound healing, in routine clinical care.
Charge-convertible polymers are a class of intelligent polymers that can convert their charges in response to a certain stimulus in their environment. This unique property endows charge-convertible ...polymer-based biomaterials with great advantages in the treatment of disease. Drug-loaded charge-convertible polymeric nanoparticles have the ability to target tumor cells by converting their surface charges from negative or neutral to positive at the tumor site. In addition, charge-convertible polymeric biomaterials can form complexes with negatively charged therapeutic agents and release them through charge conversion at the desired time and site. In this review, the properties of charge-convertible polymers and their applications in the treatment of cancer and stroke are covered. More importantly, the limitations and perspectives of charge-convertible polymeric biomaterials in future clinical applications are discussed.
This review focuses on the attachment of polymer brushes to polymeric biomaterial substrates by chemical surface modification methods for biomedical applications. In the first part of this paper, a ...general introduction to the synthesis of polymer brushes is given. Thereafter, a comprehensive overview of recent work on the chemical surface modification of polymeric biomaterials, with a focus on “grafting‐to,” “grafting‐from,” and “grafting‐through” strategies, is provided. Finally, some representative cutting‐edge biomedical applications of modified polymeric biomaterials, mainly including antifouling materials and biocompatible materials, are highlighted. On the basis of this literature study, a perspective on future trends in this field is provided.
A comprehensive overview of recent work on chemical surface modification of polymeric biomaterials, with a focus on grafting‐to, grafting‐from, and grafting‐through strategies, is provided. Furthermore, some representative cutting‐edge biomedical applications of modified polymeric biomaterials, mainly including antifouling materials and biocompatible materials, are highlighted.
Chronic wounds have been a global health threat over the past few decades, requiring urgent medical and research attention. The factors delaying the wound-healing process include obesity, stress, ...microbial infection, aging, edema, inadequate nutrition, poor oxygenation, diabetes, and implant complications. Biomaterials are being developed and fabricated to accelerate the healing of chronic wounds, including hydrogels, nanofibrous, composite, foam, spongy, bilayered, and trilayered scaffolds. Some recent advances in biomaterials development for healing both chronic and acute wounds are extensively compiled here. In addition, various properties of biomaterials for wound-healing applications and how they affect their performance are reviewed. Based on the recent literature, trilayered constructs appear to be a convincing candidate for the healing of chronic wounds and complete skin regeneration because they mimic the full thickness of skin: epidermis, dermis, and the hypodermis. This type of scaffold provides a dense superficial layer, a bioactive middle layer, and a porous lower layer to aid the wound-healing process. The hydrophilicity of scaffolds aids cell attachment, cell proliferation, and protein adhesion. Other scaffold characteristics such as porosity, biodegradability, mechanical properties, and gas permeability help with cell accommodation, proliferation, migration, differentiation, and the release of bioactive factors.
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The aim of this study was the synthesis and evaluation of entirely S-protected thiolated hydroxyethylcellulose (HEC) with low and high viscosity, as well as thiolated poly-L-lysine ...(poly-L-Lys) used as dual-acting ionic as well as thiol-disulfide exchange mediated cross-linking hydrogel.
Bis(mercaptosuccinic acid) was covalently attached to low and high viscous HECs via Fisher esterification, obtaining S-protected polymers. Poly-L-Lys-cysteine was synthesized via amidation of poly-L-Lys-HBr with cysteine (Cys). Thiolated polymers were examined in terms of cytotoxicity and rheological behavior of hydrogels containing these thiomers was evaluated with a cone-plate rheometer.
Thiomers showed less cytotoxicity compared to the corresponding unmodified polymers. Rheological studies showed that cross-linking occurred between the two polymers via thiol-disulfide exchange reactions facilitated by the complementary charges. Employing poly-L-Lys-Cys in a concentration of either 0.5 or 5% (m/v) resulted in a 34.5-fold or 17.3-fold as well as a 53.6-fold or 29.6-fold improvement in dynamic viscosity within 5 min at 37 °C on S-protected thiolated low and high viscous HEC, compared to the corresponding unmodified HECs, respectively.
By the combination of anionic S-protected thiolated polymers with a cationic thiolated polymer, dual-acting hydrogels exhibiting a time dependent increase in viscosity can be designed.
Engineered scaffolds produced by electrospinning of biodegradable polymers offer a 3D, nanofibrous environment with controllable structural, chemical, and mechanical properties that mimic the ...extracellular matrix of native tissues and have shown promise for a number of tissue engineering applications. The microscale mechanical interactions between cells and electrospun matrices drive cell behaviors including migration and differentiation that are critical to promote tissue regeneration. Recent developments in understanding these mechanical interactions in electrospun environments are reviewed, with emphasis on how fiber geometry and polymer structure impact on the local mechanical properties of scaffolds, how altering the micromechanics cues cell behaviors, and how, in turn, cellular and extrinsic forces exerted on the matrix mechanically remodel an electrospun scaffold throughout tissue development. Techniques used to measure and visualize these mechanical interactions are described. We provide a critical outlook on technological gaps that must be overcome to advance the ability to design, assess, and manipulate the mechanical environment in electrospun scaffolds toward constructs that may be successfully applied in tissue engineering and regenerative medicine.
Tissue engineering requires design of scaffolds that interact with cells to promote tissue development. Electrospinning is a promising technique for fabricating fibrous, biomimetic scaffolds. Effects of electrospun matrix microstructure and biochemical properties on cell behavior have been extensively reviewed previously; here, we consider cell-matrix interaction from a mechanical perspective. Micromechanical properties as a driver of cell behavior has been well established in planar substrates, but more recently, many studies have provided new insights into mechanical interaction in fibrillar, electrospun environments. This review provides readers with an overview of how electrospun scaffold mechanics and cell behavior work in a dynamic feedback loop to drive tissue development, and discusses opportunities for improved design of mechanical environments that are conducive to tissue development.
Cells respond to the mechanical signals from their surroundings and integrate physiochemical signals to initiate intricate mechanochemical processes. While many studies indicate that topological ...features of biomaterials impact cellular behaviors profoundly, little research has focused on the nuclear response to a mechanical force generated by a topological surface. Here, we fabricated a polymeric micropillar array with an appropriate dimension to induce a severe self-deformation of cell nuclei and investigated how the nuclear shape changed over time. Intriguingly, the nuclei of mesenchymal stem cells (MSCs) on the poly(lactide-co-glycolide) (PLGA) micropillars exhibited a significant initial deformation followed by a partial recovery, which led to an “overshoot” phenomenon. The treatment of cytochalasin D suppressed the recovery of nuclei, which indicated the involvement of actin cytoskeleton in regulating the recovery at the second stage of nuclear deformation. Additionally, we found that MSCs exhibited different overshoot extents from their differentiated lineage, osteoblasts. These findings enrich the understanding of the role of the cell nucleus in mechanotransduction. As the first quantitative report on nonmonotonic kinetic process of self-deformation of a cell organelle on biomaterials with unique topological surfaces, this study sheds new insight into cell–biomaterial interactions.
Porosity and pore size of biomaterial scaffolds play a critical role in bone formation in vitro and in vivo. This review explores the state of knowledge regarding the relationship between porosity ...and pore size of biomaterials used for bone regeneration. The effect of these morphological features on osteogenesis in vitro and in vivo, as well as relationships to mechanical properties of the scaffolds, are addressed. In vitro, lower porosity stimulates osteogenesis by suppressing cell proliferation and forcing cell aggregation. In contrast, in vivo, higher porosity and pore size result in greater bone ingrowth, a conclusion that is supported by the absence of reports that show enhanced osteogenic outcomes for scaffolds with low void volumes. However, this trend results in diminished mechanical properties, thereby setting an upper functional limit for pore size and porosity. Thus, a balance must be reached depending on the repair, rate of remodeling and rate of degradation of the scaffold material. Based on early studies, the minimum requirement for pore size is considered to be ∼100
μm due to cell size, migration requirements and transport. However, pore sizes >300
μm are recommended, due to enhanced new bone formation and the formation of capillaries. Because of vasculariziation, pore size has been shown to affect the progression of osteogenesis. Small pores favored hypoxic conditions and induced osteochondral formation before osteogenesis, while large pores, that are well-vascularized, lead to direct osteogenesis (without preceding cartilage formation). Gradients in pore sizes are recommended for future studies focused on the formation of multiple tissues and tissue interfaces. New fabrication techniques, such as solid-free form fabrication, can potentially be used to generate scaffolds with morphological and mechanical properties more selectively designed to meet the specificity of bone-repair needs.
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