Advanced healthcare materials

Việc tăng tốc và điều trị triệt để các vết thương mãn tính vẫn đang là một nhu cầu y tế lớn chưa được đáp ứng do các triệu chứng phức tạp từ rối loạn chuyển hóa của vi môi trường vết thương. Mặc dù có nhiều chiến lược và các hydrogel sinh học được phát triển, một phương pháp điều trị vết thương mãn tính hiệu quả và phổ biến vẫn là một điểm nghẽn. Với mục tiêu đẩy nhanh quá trình chữa lành vết thương mãn tính, nhiều hydrogel băng gạc có chức năng chống oxy hóa đã xuất hiện và được chứng minh là có thể tăng tốc độ chữa lành vết thương, đặc biệt là trong việc sửa chữa vết thương mãn tính. Chiến lược mới trong điều trị vết thương mãn tính do hydrogel chống oxy hóa mang lại có ý nghĩa to lớn đối với sức khỏe con người. Ở đây, ứng dụng của hydrogel chống oxy hóa trong việc sửa chữa vết thương mãn tính được thảo luận một cách hệ thống, nhằm cung cấp một tài liệu tham khảo lý thuyết quan trọng cho những đột phá tiếp theo trong việc chữa lành vết thương mãn tính.

Regenerative medicine holds the promise of engineering functional tissues or organs to heal or replace abnormal and necrotic tissues/organs, offering hope for filling the gap between organ shortage and transplantation needs. Three‐dimensional (3D) bioprinting is evolving into an unparalleled biomanufacturing technology due to its high‐integration potential for patient‐specific designs, precise and rapid manufacturing capabilities with high resolution, and unprecedented versatility. It enables precise control over multiple compositions, spatial distributions, and architectural accuracy/complexity, therefore achieving effective recapitulation of microstructure, architecture, mechanical properties, and biological functions of target tissues and organs. Here we provide an overview of recent advances in 3D bioprinting technology, as well as design concepts of bioinks suitable for the bioprinting process. We focus on the applications of this technology for engineering living organs, focusing more specifically on vasculature, neural networks, the heart and liver. We conclude with current challenges and the technical perspective for further development of 3D organ bioprinting.

The universal increase in the number of patients with nonhealing skin wounds imposes a huge social and economic burden on the patients and healthcare systems. Although, the application of traditional wound dressings contributes to an effective wound healing outcome, yet, the complexity of the healing process remains a major health challenge. Recent advances in materials and fabrication technologies have led to the fabrication of dressings that provide proper conditions for effective wound healing. The 3D‐printed wound dressings, biomolecule‐loaded dressings, as well as smart and flexible bandages are among the recent alternatives that have been developed to accelerate wound healing. Additionally, the new generation of wound dressings contains a variety of microelectronic sensors for real‐time monitoring of the wound environment and is able to apply required actions to support the healing progress. Moreover, advances in manufacturing flexible microelectronic sensors enable the development of the next generation of wound dressing substrates, known as electronic skin, for real‐time monitoring of the whole physiochemical markers in the wound environment in a single platform. The current study reviews the importance of smart wound dressings as an emerging strategy for wound care management and highlights different types of smart dressings for promoting the wound healing process.

Biomaterial‐mediated inflammation and fibrosis remain a prominent challenge in designing materials to support tissue repair and regeneration. Despite the many biomaterial technologies that have been designed to evade or suppress inflammation (i.e., delivery of anti‐inflammatory drugs, hydrophobic coatings, etc.), many materials are still subject to a foreign body response, resulting in encapsulation of dense, scar‐like extracellular matrix. The primary cells involved in biomaterial‐mediated fibrosis are macrophages, which modulate inflammation, and fibroblasts, which primarily lay down new extracellular matrix. While macrophages and fibroblasts are implicated in driving biomaterial‐mediated fibrosis, the signaling pathways and spatiotemporal crosstalk between these cell types remain loosely defined. In this review, the role of M1 and M2 macrophages (and soluble cues) involved in the fibrous encapsulation of biomaterials in vivo is investigated, with additional focus on fibroblast and macrophage crosstalk in vitro along with in vitro models to study the foreign body response. Lastly, several strategies that have been used to specifically modulate macrophage and fibroblast behavior in vitro and in vivo to control biomaterial‐mediated fibrosis are highlighted.

The paucity of cellular and molecular signals essential for normal wound healing makes severe dermatological ulcers stubborn to heal. The novel strategies of skin regenerative treatments are focused on the development of biologically responsive scaffolds accompanied by cells and multiple biomolecules resembling structural and biochemical cues of the natural extracellular matrix (ECM). Electrospun nanofibrous scaffolds provide similar architecture to the ECM leading to enhancement of cell adhesion, proliferation, migration and neo tissue formation. This Review surveys the application of biocompatible natural, synthetic and composite polymers to fabricate electrospun scaffolds as skin substitutes and wound dressings. Furthermore, the application of biomolecules and therapeutic agents in the nanofibrous scaffolds viz growth factors, genes, antibiotics, silver nanoparticles, and natural medicines with the aim of ameliorating cellular behavior, wound healing, and skin regeneration are discussed.

Hydrogels based on natural polymers have bright application prospects in biomedical fields due to their outstanding biocompatibility and biodegradability. However, the poor mechanical performances of pure natural polymer‐based hydrogels greatly limit their application prospects. Recently, a variety of strategies has been applied to prepare natural polymer‐based hydrogels with enhanced mechanical properties, which generally exhibit stiffening, strengthening, and stretchable behaviors. This article summarizes the recent progress of natural polymer‐based hydrogels with enhanced mechanical properties. From a structure point of view, four kinds of hydrogel are reviewed; double network hydrogels, nanocomposite hydrogels, click chemistry‐based hydrogels, and supramolecular hydrogels. For each typical hydrogel, its preparation, structure, and mechanical performance are introduced in detail. At the end of this article, the current challenges and future prospects of hydrogels based on natural polymers are discussed and it is pointed out that 3D printing may offer a new platform for the development of natural polymer‐based hydrogels.

Silk/polyethylene glycol (PEG) hydrogels are studied as self‐standing bioinks for 3D printing for tissue engineering. The two components of the bioink, silk fibroin protein (silk) and PEG, are both Food and Drug Administration approved materials in drug and medical device products. Mixing PEG with silk induces silk β‐sheet structure formation and thus gelation and water insolubility due to physical crosslinking. A variety of constructs with high resolution, high shape fidelity, and homogeneous gel matrices are printed. When human bone marrow mesenchymal stem cells are premixed with the silk solution prior to printing and the constructs are cultured in this medium, the cell‐loaded constructs maintain their shape over at least 12 weeks. Interestingly, the cells grow faster in the higher silk concentration (10%, w/v) gel than in lower ones (7.5 and 5%, w/v), likely due to the difference in material stiffness and the amount of residual PEG remaining in the gel related to material hydrophobicity. Subcutaneous implantation of 7.5% (w/v) bioink gels with and without printed fibroblast cells in mice reveals that the cells survive and proliferate in the gel matrix for at least 6 week postimplantation. The results suggest that these silk/PEG bioink gels may provide suitable scaffold environments for cell printing and function.

Biodegradable polymers play a pivotal role in in situ tissue engineering. Utilizing various technologies, researchers have been able to fabricate 3D tissue engineering scaffolds using biodegradable polymers. They serve as temporary templates, providing physical and biochemical signals to the cells and determining the successful outcome of tissue remodeling. Furthermore, a biodegradable scaffold also presents the fourth dimension for tissue engineering, namely time. The properties of the biodegradable polymer change over time, presenting continuously changing features during the degradation process. These changes become more complicated when different materials are combined together to fabricate a composite or heterogeneous scaffold. This review undertakes a systematic analysis of the basic characteristics of biodegradable polymers and describe recent advances in making composite biodegradable scaffolds for in situ tissue engineering and regenerative medicine. The interaction between implanted biodegradable biomaterials and the in vivo environment are also discussed, including the properties and functional changes of the degradable scaffold, the local effect of degradation on the contiguous tissue and their evaluation using both in vitro and in vivo models.

As one of the most important natural materials, cortical bone is a composite material comprising assemblies of tropocollagen molecules and nanoscale hydroxyapatite mineral crystals, forming an extremely tough, yet lightweight, adaptive and multi‐functional material. Bone has evolved to provide structural support to organisms, and therefore its mechanical properties are vital physiologically. Like many mineralized tissues, bone can resist deformation and fracture from the nature of its hierarchical structure, which spans molecular to macroscopic length‐scales. In fact, bone derives its fracture resistance with a multitude of deformation and toughening mechanisms that are active at most of these dimensions. It is shown that bone's strength and ductility originate primarily at the scale of the nano to submicrometer structure of its mineralized collagen fibrils and fibers, whereas bone toughness is additionally generated at much larger, micro‐ to near‐millimeter, scales from crack‐tip shielding associated with interactions between the crack path and the microstructure. It is further shown how the effectiveness with which bone's structural features can resist fracture at small to large length‐scales can become degraded by biological factors such as aging and disease, which affect such features as the collagen cross‐linking environment, the homogeneity of mineralization, and the density of the osteonal structures.

Patients with extensive burns rely on the use of tissue engineered skin due to a lack of sufficient donor tissue, but it is a challenge to identify reliable and economical scaffold materials and donor cell sources for the generation of a functional skin substitute. The current review attempts to evaluate the performance of the wide range of biomaterials available for generating skin substitutes, including both natural biopolymers and synthetic polymers, in terms of tissue response and potential for use in the operating room. Natural biopolymers display an improved cell response, while synthetic polymers provide better control over chemical composition and mechanical properties. It is suggested that not one material meets all the requirements for a skin substitute. Rather, a composite scaffold fabricated from both natural and synthetic biomaterials may allow for the generation of skin substitutes that meet all clinical requirements including a tailored wound size and type, the degree of burn, the patient age, and the available preparation technique. This review aims to be a valuable directory for researchers in the field to find the optimal material or combination of materials based on their specific application.