Tissue Scaffolds Research Articles

Antimicrobial Natural Hydrogels in Biomedicine: Properties, Applications, and Challenges-A Concise Review.

Natural hydrogels are widely used as biomedical materials in many areas, including drug delivery, tissue scaffolds, and particularly wound dressings, where they can act as an antimicrobial factor lowering the risk of microbial infections, which are serious health problems, especially with respect to wound healing. In this review article, a number of promising strategies in the development of hydrogels with biocidal properties, particularly those originating from natural polymers, are briefly summarized and concisely discussed. Common strategies to design and fabricate hydrogels with intrinsic or stimuli-triggered antibacterial activity are exemplified, and the mechanisms lying behind these properties are also discussed. Finally, practical antibacterial applications are also considered while discussing the current challenges and perspectives.

Fabrication and investigation of physicochemical and biological properties of3Dprinted sodium alginate‐chitosan blend polyelectrolyte complex scaffold for bone tissue engineering application

AbstractIn tissue engineering technique, a biological scaffold with appropriate composition and structure for promoting growth and differentiation of cells thereby regenerating damaged tissue, is a prime necessity. In this paper, 3D‐printed scaffolds comprising sodium alginate (SA) and chitosan (CH) biopolymers of natural origin are reported. Bioinks with varying ratios of SA and CH were prepared and scaffolds were fabricated by 3D printing. The fabricated scaffolds possess many desired properties that are vital for tissue regeneration purposes. The scaffolds possess open pore microstructures with interconnected pores and desired pore size as revealed by scanning electron microscopic image analysis. The polyelectrolyte complex formation (PEC) between SA and CH as revealed by Fourier‐transform‐infrared spectroscopic analysis is favorable as it offers a better surface for cell attachment and proliferation, and an ideal microenvironment for bone regeneration. Among the scaffolds, SA/CH with 60:40 showed controlled swelling and degradation behavior, with higher tensile strength of 0.387 ± 0.015 MPa. In vitro‐biomineralization showed superior apatite layer deposition ability over the SA/CH: 60/40 scaffold surface. The fabricated SA/CH scaffolds are hydrophilic and biocompatible as evident from the contact angle, protein adsorption, MTT assay, and cell attachment studies. However, SA/CH: 60/40 is shown to have superior biological properties compared with the other SA/CH compositions. Thus, it is concluded that 3Dv printed SA/CH: 60/40 scaffold having some superior properties and bioactivity can be used as a suitable matrix for future bone tissue regeneration applications.

A Novel, Image-Based Method for Characterization of the Porosity of Additively Manufactured Bone Scaffolds With Complex Microstructures

Abstract Bone tissue engineering has emerged as a promising strategy for the treatment of osseous fractures, defects, and ultimately diseases caused by, for example, bone tumor resection, accident trauma, and congenital malformation. Additive fabrication of stem cell-seeded, osteoconductive porous scaffolds has been an effective method in clinical practice for the treatment of bone pathologies (such as osteoporosis, osteoarthritis, and rheumatic diseases). Porosity is known to be one of the main morphological characteristics of bone tissues, which affects the functional performance of an implanted bone scaffold. Hence, in situ detection and quantification of scaffold porosity implemented to ensure functional integrity prior to implantation/surgery is an unavoidable need. The objective of this research work is to introduce a robust, image-based method for identification and subsequently characterization of the surface porosity and dimensional accuracy of additively manufactured bone tissue scaffolds, with a focus on pneumatic micro-extrusion (PME) process. It was observed that the presented method would be capable of detecting complex individual pores based on a micrograph. Using the proposed method, not only were scaffold pores detected, but also scaffold porosity was characterized on the basis of various defined quality metrics/traits (such as the relative standard deviation of distance to the nearest pore). The proposed method was validated by contrasting its performance in “surface pore detection” against that of a standard method, tested on a complex benchmark in four different simulated lighting environments. Besides, the performance of the method in terms of “pore filling” was compared to that of a standard method, tested on a real PME-fabricated bone scaffold. It was observed that the proposed method had a better performance in pore filling, detection, and consolidation. Overall, the outcomes of this work pave the way for high-resolution fabrication of patient-specific, structurally complex, and porous bone scaffolds with easily validatable, functional, and medical properties for the treatment of bone pathologies.

The highly absorbent polyurethane/polylactic acid blend electrospun tissue scaffold for dermal wound dressing

The highly absorbent polyurethane/polylactic acid blend electrospun tissue scaffold for dermal wound dressing

Elucidation of Structure–Function Relationships of Hyaluronic Acid-Based Polymers via Combinatorial Approaches

Hydrogels have been identified as biomaterials of significant interest owing to their unique properties─hydrophilic structures, high degree of structural flexibility, low toxicity, biocompatibility─that qualify them as ideal candidates in a wide range of biomedical and pharmaceutical applications from wound dressing surface coatings, to drug delivery composites, and tissue scaffolds. However, such desired properties of hydrogels simultaneously endow these materials with inherent shortcomings that have hindered their prolific implementation in even more industrial applications; specifically, hydrogels suffer from low mechanical stability and loss of native function upon exposure to industrial solvents. One proposed technique to overcome these challenges and thus functionalize hydrogels to increased their wider range of industrial applications is their chemical modification to elicit controllable changes in their structure and function to thus fulfill the user-defined end goal. The chemical modification strategy further drives the need for an in-depth understanding of the physical and chemical phenomena that control the assembly of modified biopolymers and thus determine their functionality. We hypothesize that a combinatorial approach employing both molecular dynamics (MD) simulations and analytical techniques could be used to probe the self-assembly of alkyl chain-modified hyaluronic acid (HYA)─model biopolymer chosen for its hydrophilicity, relative abundance, biocompatibility, and periodic carboxylate reactive group─and thus will allow us to control the assembly dynamics and its end structure properties when alkyl-chain-modified HYA networks are to be constructed, especially porosity, average pore aperture size, and accessible surface area. For this purpose, modified HYA chains were synthesized via (1)-ethyl-3-(3-dimethylaminopropyl) carbodiimide chloride (EDC)-mediated amine group attachment of dodecylamine to the periodic carboxylate group onto the HYA backbone. Material characterization including Fourier transform infrared spectroscopy, nuclear magnetic resonance, and thermogravimetric analysis was conducted to confirm the expected EDC reaction chemistry and further assess the water uptake capacity of the resulting modified hydrogels. MD simulations of both unmodified HYA and modified HYA chains─with varied lengths of attached alkyl groups as well as varied degrees of alkyl group substitution on the HYA backbone─were carried out to analyze the self-assembly dynamics of such chains and thus determine how differences in chemical modification eventuate the critical differences in the end structure properties of the resulting networks. Our findings demonstrate that targeted, atomic-level investigation and corroborated analytical analyses of the assembly of chemically modified hydrogels are necessary to develop the next generation of fully optimized biomaterials that have extended applicability in industrial settings.

Fabrication and Properties of a Hybrid Biocompatible Nanofiber Mesh Constituted of Polycaprolactone and Self-Assembly Peptide

Conventional therapeutic methods for organ and tissue deficiencies include surgical reconstruction, organ transplantation, medical devices treatment, synthetic prosthesis and so on, of which the application is limited when donors exhibit a low availability and impaired organs and tissues cannot well perform their functions. Tissue Engineering (TE) can harmonize with regional organs or tissues, ensure optimal degradation time for novel structure rebirth, facilitate cell adhesiveness, contribute to cell procreation and differentiation in tissue scaffolds, etc., making it an alternative option for treating pathological obstacles. Artificial polymers such as polycaprolactone (PCL) and nature materials such as peptides are adopted for the fabrication of nanofiber scaffolds. The study first engineered porous PCL scaffolds for examining the fiber morphology and the diameter alternations considering the change of single variable condition of the solution concentration, voltage and electrode distance, etc., thereby finding the basic conditions for producing nanofiber scaffolds with good formation. With the increase in solution concentration, the more obvious molecule entanglement can limit the jet stretching, thereby enlarging the fiber diameters. Voltage negatively impacts the fiber diameters, and elevated voltage can strengthen the electric intensity, thereby leading to a complete stretching of cone jets and making fiber diameters thinner. Besides, increased electrode distance is followed by expanded flight distance and decreased electrode intensity (constant voltage), as a result, fibers become narrower. Nanofiber substance exhibits the optimal performance under the condition of solution concentration: 6%, voltage: 50kV, and electrode distance: 150mm. Subsequently, nanofiber scaffolds were fabricated based on the respective preparation of PCL/P11-4 and PCL/P11-8 polymer solutions. Both P11-4 and P11-8 presented uneven distribution in PCL scaffolds, which involved various PCL nanofiber substances with abundant peptides. PCL nanofiber scaffolds saw the breakage of P11-4 and P11-8 fibers.

Bionic artificial penile Tunica albuginea

Bionic artificial penile Tunica albuginea

One-pot synthesis of injectable self-healing thermoresponsive halloysite nanotube-reinforced nanocomposite hydrogels for tissue engineering

Injectable hydrogels that can fill irregular defects through a minimally invasive approach are of particular interest to replace invasive surgeries in tissue scaffold implantation. However, the use of injectable hydrogels is often restricted by the drawback of having poor mechanical properties. In this work, a novel halloysite nanotube (Hal)-based hydrogel was developed using bacterial cellulose and gelatin, as well as acid-treated Hal to serve a dual purpose of providing structural support for tissue regeneration while offering possibilities for drug delivery at a local site. The fabricated hydrogels were then analyzed physically and morphologically for injectability, gelling ability, self-healing capability, as well as composition characterization, surface morphology, mechanical performance, and biodegradability. Analyses revealed that all the hydrogels could be injected as a liquid, with an in-situ sol-gel transition occurring after 10 min at 37 °C. Furthermore, the honeycomb-like structure of the hydrogel and the rougher surface where Hal dispersed over the surfaces could also provide sufficient space and anchorage sites to facilitate cell attachment. With the moisture content reaching up to 85–92%, the hydrogels could provide a moist recovery environment for the healing process. More importantly, the incorporation of Hal greatly improved the compressive strength and Young's modulus up to 60% and 40%, respectively. Furthermore, antibiotic-loaded hydrogels demonstrated effective antimicrobial activity against Staphylococcus epidermidis, methicillin-susceptible Staphylococcus aureus (MSSA), and methicillin-resistant S. aureus (MRSA). Collectively, such hydrogels with a minimally invasive delivery approach and the potential to aid in tissue regeneration can be applied in biomedical and tissue engineering applications, along with a combined local delivery of antimicrobial agents in the near future.

Electro-conductive silica nanoparticles-incorporated hydrogel based on alginate as a biomimetic scaffold for bone tissue engineering application

An innovative electrically conductive hydrogel was fabricated through the incorporation of silica nanoparticles (SiO2 NPs) and poly(aniline-co-dopamine) (PANI-co-PDA) into oxidized alginate (OAlg) as a biomimetic scaffold for bone tissue engineering application. The developed self-healing chemical hydrogel was characterized by FTIR, SEM, TEM, XRD, and TGA. The electrical conductivity and swelling ratio of the hydrogel were obtained as 1.7 × 10−3 S cm−1 and 130%, respectively. Cytocompatibility and cell proliferation potential of the developed scaffold were approved by MTT assay using MG-63 cells. FE-SEM imaging approved the potential of the fabricated scaffold for hydroxyapatite (HA) formation and bioactivity induction through immersing in SBF solution.

Additive manufacturing technologies with emphasis on stereolithography 3D printing in pharmaceutical and medical applications: A review

Three-dimensional (3D) printing or Additive Manufacturing (AM) technology is an innovative tool with great potential and diverse applications in various fields. As 3D printing has been burgeoning in recent times, a tremendous transformation can be envisaged in medical care, especially the manufacturing procedures leading to personalized medicine. Stereolithography (SLA), a vat-photopolymerization technique, that uses a laser beam, is known for its ability to fabricate complex 3D structures ranging from micron-size needles to life-size organs, because of its high resolution, precision, accuracy, and speed. This review presents a glimpse of varied 3D printing techniques, mainly expounding SLA in terms of the materials used, the orientation of printing, and the working mechanisms. The previous works that focused on developing pharmaceutical dosage forms, drug-eluting devices, and tissue scaffolds are presented in this paper, followed by the challenges associated with SLA from an industrial and regulatory perspective. Due to its excellent advantages, this technology could transform the conventional “one dose fits all” concept to bring digitalized patient-centric medication into reality.

Automated Cell Viability Analysis in Tissue Scaffolds

Image processing techniques are frequently used for extracting quantitative information (cell area, cell size, cell counting, etc.) from different types of microscopic images. Image analysis of cell biology and tissue engineering is time consuming and requires personal expertise. In addition, evaluation of the results may be subjective. Therefore, computer-based learning applications have been rapidly developed in recent years. In this study, Confocal Laser Scanning Microscope (CLSM) images of the viable pre-osteoblastic mouse MC3T3-E1 cells in 3D bioprinted tissue scaffolds, captured from a bone tissue regeneration study, were analyzed by using image processing techniques. The goal of this study is to develop a reliable and fast algorithm for semi-automatic analysis of CLSM images. Percentages of live and dead cell areas in the scaffolds were determined with image correlation, and then, total cell viabilities were calculated. The other goal of this study is to determine the depth profile of viable cells in 3D tissue scaffold. Manual measurements of four different analysts were obtained. The measurement variations of analysts, also known as the coefficient of variation, were determined from 13.18% to 98.34% for live cell images and from 9.75% to 126.02% for dead cell images. To overcome this subjectivity, a semi-automatic algorithm was developed. Consequently, cross-sectional image sets of three different types of tissue scaffolds were analyzed. As a result, maximum cell viabilities were obtained at intervals of 63 µm and 90 µm from the scaffold surface.

Study of Thermal, Phase Morphological and Mechanical Properties of Poly(L-lactide)-b-Poly(ethylene glycol)-b-Poly(L-lactide)/Poly(ethylene glycol) Blend Bioplastics

A poly(L-lactide)-b-poly(ethylene glycol)-b-poly(L-lactide)(PLLA-PEG-PLLA) block copolymer has great potential for use as a flexible bioplastic. Highly flexible bioplastics are required for flexible packaging applications. In this work, a PEG was incorporated into block copolymer as a plasticizer by solvent casting. PLLA-PEG-PLLA/ PEG blends with different blend ratios were prepared, and the plasticizing effect and miscibility of PEG in block copolymer were intensively investigated compared to PLLA/PEG blends. The results indicated that the PEG was an effective plasticizer for the block copolymer. The blending of PEG decreased glass-transition temperature and accelerated the crystallization of both the PLLA and PLLA-PEG-PLLA matrices. The PEG was completely miscible when blended with block copolymer and it improved thermal stability of the block copolymer matrix but not of the PLLA matrix. Film extensibility of PLLA-PEG-PLLA/PEG blends steadily increased as the PEG ratio increased. These non-toxic and highly flexible PLLA-PEG-PLLA/PEG bioplastics are promising candidates for several applications such as biomedical devices, tissue scaffolds and packaging materials.

The Novel Use of Cryopreserved Human Allograft in Extensive Hurley Stage III Hidradenitis Suppurativa

Introduction. HS is a debilitating dermatologic condition in which apocrine sweat glands become occluded, leading to severe inflammation. Treatment usually ranges from conservative management to surgical intervention with the goal of treating existing lesions while reducing the rate of recurrence, progression, and scarring. Depending on the surface area involved, autologous skin grafting may be difficult when donor sites are limited due to the extent of disease, previous surgery, or scarring. This case report examines the efficacy of cryopreserved human allograft as a surgical treatment of extensive HS. Case Report. A 37-year-old man presented with severe, refractory Hurley stage III HS in which cryopreserved human allograft was used to aid in wound contracture and granulation tissue formation. In addition, its use improved contour deformities and served as a bridge to autologous skin grafting, minimizing donor site size and morbidity. Conclusions. While autologous skin grafting is necessary for final wound closure, the use of cryopreserved human allograft provides biologic wound management that aids as a bridge to autologous skin grafting. As such, the authors advocate its use as a tissue scaffold in the management of severe, extensive HS and other dermatologic conditions requiring skin excision.

Optimization of Fluorapatite/Bioactive Glass Nanocomposite Foams as Bone Tissue Scaffold: An in Vivo Study.

The present study investigated the suitability of nanocomposite foams of fluorapatite and bioactive glass (FA /BG) in different weight ratios as scaffolds for bone tissue in rat tibia regeneration to determine the optimal composition. FA and BG nano powders with a weight ratio of 25% FA/75% BG (compound 1) and 75% FA/25% BG (compound 2) were used as precursors for gel casting to produce nanocomposite foams. Thirty rats were randomly divided into two equal groups. Disk-shaped samples of each compound were implanted into the tibias of 15 rats. After 15, 30, or 60 days, five rats from each group were sacrificed and subjected to radiological, histopathological, and histomorphometrical examination. Data were analyzed using SPSS software. No foreign body reaction was observed in either group at all intervals, and the bone-biomaterial junction was direct. Overall, the inflammation rate, and the number of blood vessels, osteoblasts, and osteoclasts decreased over time in both groups. However, the number of osteocytes, trabecular bone thickness, and the percentage of new bone formation increased, in contrast to the remaining biomaterial percentage. Most of the changes in the group implanted with compound 2 were significantly more significant and faster than in the other group. Although the composite with the higher percentage of FA was superior to the composite with the higher percentage of BG, considering the results of our previous similar studies, the composite with the same percentage of FA and BG is more favorable to be used as a substitute for bone tissue in the body.

Methylcellulose/agarose hydrogel loaded with short electrospun PLLA/laminin fibers as an injectable scaffold for tissue engineering/3D cell culture model for tumour therapies

This research aimed at designing and fabricating a smart thermosensitive injectable methylcellulose/agarose hydrogel system loaded with short electrospun bioactive PLLA/laminin fibers as a scaffold for tissue engineering applications or 3D cell culture models. Considering ECM-mimicking morphology and chemical composition, such a scaffold is capable of ensuring a hospitable environment for cell adhesion, proliferation, and differentiation. Its viscoelastic properties are beneficial from the practical perspective of minimally invasive materials that are introduced to the body via injection. Viscosity studies showed the shear-thinning character of MC/AGR hydrogels enabling the potential injection ability of highly viscous materials. Injectability tests showed that by tuning the injection rate, even a high amount of short fibers loaded inside of hydrogel could be efficiently injected into the tissue. Biological studies showed the non-toxic character of composite material with excellent viability, attachment, spreading, and proliferation of fibroblasts and glioma cells. These findings indicate that MC/AGR hydrogel loaded with short PLLA/laminin fibers is a promising biomaterial for both tissue engineering applications and 3D tumor culture models.

Evaluation of photochemically cross-linked collagen/gold nanoparticle composites as potential skin tissue scaffolds.

Collagen type I is the main structural unit in skin tissue and is therefore used preferentially in skin tissue scaffolds. However, collagen-based 3D scaffolds have weak aqueous stability and degradation profiles in their uncross-linked states and chemical cross-linking reagents arise toxicity concerns, which generally restrict the spectrum of their biomedical applicability. Here, the research goal is to photochemically cross-link collagen type I with rose bengal (RB) when subjected to green laser light and to investigate the effect of silk sericin-capped gold nanoparticles (S-AuNP) when incorporated into scaffolds on the cross-linking process and thus on the scaffold properties. All the collagen scaffolds, that is plain collagen (C), collagen/S-AuNP (C-Au), cross-linked collagen (C-RBL), and cross-linked collagen/S-AuNP (C-AuRBL) were characterized for their potential as skin tissue scaffolds. C-AuRBL group had the best thermal stability, resistance to enzymatic degradation, and more uniform pore size distribution. None of the groups had cytotoxicity (cell viability > 70%) regarding the microscopic observations and MTT cell viability assays for L929 fibroblasts. L929 fibroblasts and primary adult human epidermal keratinocytes (HEKa) were also separately seeded on C-AuRBL scaffolds and according to microscopy results, they could support the stimulation of adhesion, morphological changes, and spreading of both cells, thereby encouraging the usage of this fabrication strategy for prospective skin tissue scaffolds.

Personalized 3D printed bone scaffolds: A review.

3D printed bone scaffolds have the potential to replace autografts and allografts because of advantages such as unlimited supply and the ability to tailor the scaffolds' biochemical, biological and biophysical properties. Significant progress has been made over the past decade in additive manufacturing techniques to 3D print bone grafts, but challenges remain in the lack of manufacturing techniques that can recapitulate both mechanical and biological functions of native bones. The purpose of this review is to outline the recent progress and challenges of engineering an ideal synthetic bone scaffold and to provide suggestions for overcoming these challenges through bioinspiration, high-resolution 3D printing, and advanced modeling techniques. The article provides a short overview of the progress in developing the 3D printed scaffolds for the repair and regeneration of critical size bone defects. STATEMENT OF SIGNIFICANCE: Treatment of critical size bone defects is still a tremendous clinical challenge. To address this challenge, diverse sets of advanced manufacturing approaches and materials have been developed for bone tissue scaffolds. 3D printing has sparked much interest because it provides a close control over the scaffold's internal architecture and in turn its mechanical and biological properties. This article provides a critical overview of the relationships between material compositions, printing techniques, and properties of the scaffolds and discusses the current technical challenges facing their successful translation to the clinic. Bioinspiration, high-resolution printing, and advanced modeling techniques are discussed as future directions to address the current challenges.

Advances in hydrogels for the treatment of periodontitis.

Periodontitis is the second most prevalent oral disease and can cause serious harm to human health. Hydrogels are excellent biomaterials that can be used for periodontitis as drug delivery platforms to achieve inflammation control through high drug delivery efficiency and sustained drug release and as tissue scaffolds to achieve tissue remodelling through encapsulated cell wrapping and effective mass transfer. In this review, we summarize the latest advances in the treatment of periodontitis with hydrogels. The pathogenic mechanisms of periodontitis are introduced first, followed by the recent progress of hydrogels in controlling inflammation and tissue reconstruction, in which the specific performance of hydrogels is discussed in detail. Finally, the challenges and limitations of hydrogels for clinical applications in periodontitis are discussed and possible directions for development are proposed. This review aims to provide a reference for the design and fabrication of hydrogels for the treatment of periodontitis.

Computational fluid dynamics analysis of the fluid environment of 3D printed tissue scaffolds within a perfusion bioreactor: the effect of pore shape

Computational fluid dynamics analysis of the fluid environment of 3D printed tissue scaffolds within a perfusion bioreactor: the effect of pore shape

Application of silk fibroin composite scaffold in bone tissue engineering

As a natural protein, silk protein has superior biocompatibility, biodegradability and mechanical properties, and can be used in different forms for bone tissue repair in bone tissue engineering as a good biomaterial. The treatment of bone defect has always been a serious challenge for orthopedic surgeons. However, the traditional treatment of bone defect is autologous bone and bone allograft, with limited source and secondary injury with sampling site; the allograft faces ethical problems, rejection, and viral transmission risk. Tissue engineering is an important means to solve tissue and organ defects. It establishes a three-dimensional space complex composed of cells and biological materials and fills the defects, so as to repair the effect Bone tissue scaffold with filim protein plays a huge role in orthopedics, and is expected to bring good news to more patients with bone diseases in the future. In this paper, we review the structural characteristics, biological properties and applications of filamentous proteins in bone tissue engineering.