Injectable Hydrogels for Cardiac Tissue Engineering

In light of the limited efficacy of current treatments for cardiac regeneration, tissue engineering approaches have been explored for their potential to provide mechanical support to injured cardiac tissues, deliver cardio‐protective molecules, and improve cell‐based therapeutic techniques. Injectable hydrogels are a particularly appealing system as they hold promise as a minimally invasive therapeutic approach. Moreover, injectable acellular alginate‐based hydrogels have been tested clinically in patients with myocardial infarction (MI) and show preservation of the left ventricular (LV) indices and left ventricular ejection fraction (LVEF). This review provides an overview of recent developments that have occurred in the design and engineering of various injectable hydrogel systems for cardiac tissue engineering efforts, including a comparison of natural versus synthetic systems with emphasis on the ideal characteristics for biomimetic cardiac materials.     

骨组织工程支架材料研究进展*

骨在组织工程中得到了非常广泛、深入的研究.支架材料与许多可降解材料一起也在进行探索性研究.用于骨组织工程的生物材料可以是三维多孔的刚硬材料,也可以是可注射材料.本文从聚合物角度综述了骨组织工程对支架材料的基本要求,用于骨组织工程的可降解生物材料、支架材料的设计和制备技术以及支架材料的表面修饰等方面的研究进展.     

Cellulose-Based Composites as Scaffolds for Tissue Engineering: Recent Advances

Today, numerous studies have focused on the design of novel scaffolds for tissue engineering and regenerative medicine applications; however, several challenges still exist in terms of biocompatibility/cytocompatibility, degradability, cell attachment/proliferation, nutrient diffusion, large-scale production, and clinical translation studies. Greener and safer technologies can help to produce scaffolds with the benefits of cost-effectiveness, high biocompatibility, and biorenewability/sustainability, reducing their toxicity and possible side effects. However, some challenges persist regarding their degradability, purity, having enough porosity, and possible immunogenicity. In this context, naturally derived cellulose-based scaffolds with high biocompatibility, ease of production, availability, sustainability/renewability, and environmentally benign attributes can be applied for designing scaffolds. These cellulose-based scaffolds have shown unique mechanical properties, improved cell attachment/proliferation, multifunctionality, and enhanced biocompatibility/cytocompatibility, which make them promising candidates for tissue engineering applications. Herein, the salient developments pertaining to cellulose-based scaffolds for neural, bone, cardiovascular, and skin tissue engineering are deliberated, focusing on the challenges and opportunities.     

Novel Poly(amidoamine)-Based Hydrogels as Scaffolds for Tissue Engineering

Summary: Poly(amidoamine)s are biocompatible biodegradable polymers, which can be easily functionalized with a number of bioactive and biomimetic compounds. Co-polymerization of these polymers with 4-aminobutyl guanidine (agmatine) leads to an RGD mimicking structure. Hydrogels based on this structure showed an enhanced cell adhesion and could be chemically linked to a glass substrate to create a bioadhesive support for cell growth. Preliminary optimization and cell adhesion tests on Madin-Darby Canine Kidney cells were performed, both on functionalized and non-functionalized structures, with promising results.     

Glycosaminoglycan-Based Cryogels as Scaffolds for Cell Cultivation and Tissue Regeneration

Cryogels are a class of macroporous, interconnective hydrogels polymerized at sub-zero temperatures forming mechanically robust, elastic networks. In this review, latest advances of cryogels containing mainly glycosaminoglycans (GAGs) or composites of GAGs and other natural or synthetic polymers are presented. Cryogels produced in this way correspond to the native extracellular matrix (ECM) in terms of both composition and molecular structure. Due to their specific structural feature and in addition to an excellent biocompatibility, GAG-based cryogels have several advantages over traditional GAG-hydrogels. This includes macroporous, interconnective pore structure, robust, elastic, and shape-memory-like mechanical behavior, as well as injectability for many GAG-based cryogels. After addressing the cryogelation process, the fabrication of GAG-based cryogels and known principles of GAG monomer crosslinking are discussed. Finally, an overview of specific GAG-based cryogels in biomedicine, mainly as polymeric scaffold material in tissue regeneration and tissue engineering-related controlled release of bioactive molecules and cells, is provided.     

Development of Channeled Nanofibrous Scaffolds for Oriented Tissue Engineering

A tissue‐engineering scaffold resembling the structure of the natural extracellular matrix can often facilitate tissue regeneration. Nerve and tendon are oriented micro‐scale tissue bundles. In this study, a method combining injection molding and thermally induced phase separation techniques is developed to create single‐ and multiple‐channeled nanofibrous poly(L ‐lactic acid) scaffolds. The overall shape, the number and spatial arrangement of channels, the channel wall matrix architecture, the porosity and mechanical properties of the scaffolds are all tunable. The porous NF channel wall matrix provides an excellent microenvironment for protein adsorption and the attachment of PC12 neuronal cells and tendon fibroblast cells, showing potential for neural and tendon tissue regeneration.

     

Functionalized Synthetic Biodegradable Polymer Scaffolds for Tissue Engineering

Scaffolds (artificial ECMs) play a pivotal role in the process of regenerating tissues in 3D. Biodegradable synthetic polymers are the most widely used scaffolding materials. However, synthetic polymers usually lack the biological cues found in the natural extracellular matrix. Significant efforts have been made to synthesize biodegradable polymers with functional groups that are used to couple bioactive agents. Presenting bioactive agents on scaffolding surfaces is the most efficient way to elicit desired cell/material interactions. This paper reviews recent advancements in the development of functionalized biodegradable polymer scaffolds for tissue engineering, emphasizing the syntheses of functional biodegradable polymers, and surface modification of polymeric scaffolds.

     

Characterization of Poly(vinyl alcohol)/Chitosan Hydrogels as Vascular Tissue Engineering Scaffolds

In this study, PVA/Chitosan hydrogels were fabricated by freeze/thaw cycles and further crosslinking with a KOH/Na₂SO₄ coagulation bath and the effect of freeze/thaw cycle number on cell behaviour was evaluated. The surface of the hydrogels were further modified with Collagen type I adsorption and seeded with bovine aortic vascular smooth muscle and endothelial cells. Increasing the number of freeze/thaw cycles resulted in a marked change in surface morphology, hydrophilicity and protein adsorption. Collagen coating caused an increase in initial attachment and proliferation. We concluded that hydrogels that have undergone 3 freeze/thaw cycles were optimum for cell attachment both in the presence and the absence of coating.     

Polydopamine-Coated Poly-Lactic Acid Aerogels as Scaffolds for Tissue Engineering Applications

Poly-L-lactic acid (PLLA) aerogel-based scaffolds were obtained from physical PLLA gels containing cyclopentanone (CPO) or methyl benzoate (BzOMe) molecules. An innovative single step method of solvent extraction, using supercritical CO₂, was used to achieve cylindrical monolithic aerogels. The pore distribution and size, analyzed by SEM microscopy, were found to be related to the crystalline forms present in the physical nodes that hold the gels together, the stable α’-form and the metastable co-crystalline ε-form, detected in the PLLA/BzOMe and PLLA/CPO aerogels, respectively. A higher mechanical compressive strength was found for the PLLA/CPO aerogels, which exhibit a more homogenous porosity. In vitro biocompatibility tests also indicated that monolithic PLLA/CPO aerogels exhibited greater cell viability than PLLA/BzOMe aerogels. An improved biocompatibility of PLLA/CPO monolithic aerogels was finally observed by coating the surface of the aerogels with polydopamine (PDA) obtained by the in situ polymerization of dopamine (DA). The synergistic effect of biodegradable polyester (PLLA) and the biomimetic interface (PDA) makes this new 3D porous scaffold, with porosity and mechanical properties that are tunable based on the solvent used in the preparation process, attractive for tissue engineering applications.     

Modified-Hydroxyapatite-Chitosan Hybrid Composite Interfacial Coating on 3D Polymeric Scaffolds for Bone Tissue Engineering

Three dimensional (3D) scaffolds have huge limitations due to their low porosity, mechanical strength, and lack of direct cell-bioactive drug contact. Whereas bisphosphonate drug has the ability to stimulate osteogenesis in osteoblasts and bone marrow mesenchymal stem cells (hMSC) which attracted its therapeutic use. However it is hard administration low bioavailability, and lack of site-specificity, limiting its usage. The proposed scaffold architecture allows cells to access the bioactive surface at their apex by interacting at the scaffold's interfacial layer. The interface of 3D polycaprolactone (PCL) scaffolds has been coated with alendronate-modified hydroxyapatite (MALD) enclosed in a chitosan matrix, to mimic the native environment and stupulate the through interaction of cells to bioactive layer. Where the mechanical strength will be provided by the skeleton of PCL. In the MALD composite's hydroxyapatite (HAP) component will govern alendronate (ALD) release behavior, and HAP presence will drive the increase in local calcium ion concentration increases hMSC proliferation and differentiation. In results, MALD show release of 86.28 ± 0.22. XPS and SEM investigation of the scaffold structure, shows inspiring particle deposition with chitosan over the interface. All scaffolds enhanced cell adhesion, proliferation, and osteocyte differentiation for over a week without in vitro cell toxicity with 3.03 ± 0.2 kPa mechanical strength.     

Self‐Healing Supramolecular Hydrogels for Tissue Engineering Applications

Self‐healing supramolecular hydrogels have emerged as a novel class of biomaterials that combine hydrogels with supramolecular chemistry to develop highly functional biomaterials with advantages including native tissue mimicry, biocompatibility, and injectability. These properties are endowed by the reversibly cross‐linked polymer network of the hydrogel. These hydrogels have great potential for realizing yet to be clinically translated tissue engineering therapies. This review presents methods of self‐healing supramolecular hydrogel formation and their uses in tissue engineering as well as future perspectives.     

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.     

组织工程三维多孔支架的制备方法和技术进展

组织工程的关键技术之一在于将具有良好生物相容性和生物降解吸收性能的生物材料制备成具有特定形状和相连孔结构的三维多孔细胞支架（细胞外基质替代物）。本文着眼于多孔支架制备方法分别与多孔支架孔结构和外形的内在联系，从致孔和外形成型两个层次对组织工程多孔支架的制备方法和技术新近的研究进展进行了综述。     

Recent Strategies in Fabrication of Gradient Hydrogels for Tissue Engineering Applications

Hydrogels are widely used as scaffold in tissue engineering field because of their ability to mimic the cellular microenvironment. However, mimicking a completely natural cellular environment is complicated due to the differences in various physical and chemical properties of cellular environments. Recently, gradient hydrogels provide excellent heterogeneous environment to mimic the different cellular microenvironments. To create hydrogels with an anisotropic distribution, gradient hydrogels have been widely developed by adopting several gradient generation techniques. Herein, the various gradient hydrogel fabrication techniques, including dual syringe pump systems, microfluidic device, photolithography, diffusion, and bio‐printing are summarized. As the effects of gradient 3D hydrogels with stems have been reviewed elsewhere, this review focuses principally on gradient hydrogel fabrication for multi‐model tissue regeneration. This review provides new insights into the key points for fabrication of gradient hydrogels for multi‐model tissue regeneration.     

Multi-Material Scaffolds for Tissue Engineering

A trend in developing biocompatible scaffolds for tissue engineering has been to seek an ideal single material for which a given cell type will exhibit favorable behavior. While an ideal single material has proven elusive, scaffold manufacture using combinations of specialist materials can produce more versatile structures. By controlling the percentage and architecture of material components, mechanical properties, cell attachment, and proliferation may be optimized for a given function. Three specialist materials, poly-ϵ-caprolactone (PCL), fibrin, and alginate, were incorporated into multi-component scaffolds for a series of experiments testing each component with culture of fibroblasts. The rigid and formable PCL provided structure, the fibrin pore-filler allowed for cell attachment, and alginate thread provided a nutrient transfer pathway in lieu of a vascular system. The efficacy of these scaffolds was judged on fibroblast distribution and population after 7-12 days of culture.     

组织工程用水凝胶材料

综述了目前用于组织工程支架材料的水凝胶,包括胶原和明胶、透明质酸盐、海藻酸盐,琼脂糖和壳聚糖等天然水凝胶,聚丙烯酸及其衍生物、聚氧化乙烯及其衍生共聚物、聚乙烯醇、聚磷腈和合成多肽等合成水凝胶,并介绍了可注射性组织工程水凝胶。