Biological Scaffolds Research Articles

Novel Thermosensitive Hydrogel Promotes Spinal Cord Repair by Regulating Mitochondrial Function.

The repair of spinal cord injury (SCI) is still a tough clinical challenge and needs innovative therapies. Mitochondrial function is significantly compromised after SCI and has emerged as an important factor causing neuronal apoptosis and hindering functional recovery. In this study, umbilical cord mesenchymal stem cells (UCMSC), which are promising seed cells for nerve regeneration, and basic fibroblast growth factor (bFGF) that have been demonstrated to have a variety of effects on neural regeneration were jointly immobilized in extracellular matrix (ECM) and heparin-poloxamer (HP) to create a polymer bioactive system that brings more hope and possibility for the treatment of SCI. Our results in vitro and in vivo showed that the UCMSC-bFGF-ECM-HP thermosensitive hydrogel has good therapeutic effects, mainly in reducing apoptosis and improving the mitochondrial function. It showed promising utility for the functional recovery of impaired mitochondrial function by promoting mitochondrial fusion, reducing pathological mitochondrial fragmentation, increasing mitochondrial energy supply, and improving the metabolism of MDA, LDH, and ROS. In addition, we uncovered a distinct molecular mechanism underlying the protective effects associated with activating p21-activated kinase 1 (PAK1) and mitochondrial sirtuin 4 (SIRT4) by the UCMSC-bFGF-ECM-HP hydrogel. The expansion of new insights into the molecular relationships between PAK1 and SIRT4, which links the mitochondrial function in SCI, can lay the foundation for future applications and help to provide promising interventions of stem-cell-based biological scaffold therapies and potential therapeutic targets for the clinical formulation of SCI treatment strategies.

Diselenide as a Dual Functional Mechanophore Capable of Stress Self-Reporting and Self-Strengthening in Polyurethane Elastomers

Diselenide as a Dual Functional Mechanophore Capable of Stress Self-Reporting and Self-Strengthening in Polyurethane Elastomers

An aorta ECM extracted hydrogel as a biomaterial in vascular tissue engineering application.

Biological scaffolds have been undergoing significant growth in tissue engineering applications over the last years. Biopolymers extracted from ECM with various protein factors and other biological agents have been active in restoring damaged tissue. In the present study, bioactive scaffold is prepared from bovine aorta extracted natural polymeric hydrogel with advantages of availability and cost-effectiveness. The biological scaffolds were prepared through freeze-drying method to make a 3D sponge with appropriate structure, well-defined architecture and interconnected pores for vascular tissue engineering, and studied the effect of aorta hydrogel concentrations (1, 2, 3, and 4% w/v) on the scaffolds. The prepared biological scaffolds were analyzed by mechanical tests, FTIR, SEM, porosity and PBS absorption. Moreover, the morphology and proliferation of human umbilical vein cord cells on the 3D sponges were investigated. Histological analysis including, Masson trichrome (MT), hematoxylin and eosin (H&E), Verhoeff/Van Gieson (VVG) and alcian blue (AB) revealed that during this process the main components of aorta extracellular matrix containing collagen, elastin, and glycosaminoglycan were well preserved. The obtained results revealed that the scaffolds porosity were more than 90%. The Aorta-ECM4% enabled HUVECs to survive, proliferate and migrate better than 2% and 3% aorta-ECM.

Polysaccharides, as biological macromolecule-based scaffolding systems in heart valve tissue engineering: a review

Polysaccharides, as biological macromolecule-based scaffolding systems in heart valve tissue engineering: a review

3D printer nozzle modification to obtain scaffolds for use in regenerative medicine

Use biological or synthetic scaffolds to conduct cellular events of the regenerative process constitute one of the major strategies in regenerative medicine area. Customized scaffolds built by additive manufacturing prove to be a great solution to this problem. Two desired features that aid in scaffold’s biocompatibility are the surface roughness and the geometric characteristic of the topography, usually achieved by a chemical procedure performed after printing. This research presented a modification on a 3D printer nozzle for directly generating an external topography in the extruded filaments, eliminating the need for an additional post-processing step. Cell morphology and viability on supports printed by the proposed and conventional method were evaluated in in vitro experiments and the new nozzle proved to be efficient in generating printed filaments with a degree of cytocompatibility superior to those obtained by conventional filaments.

A collagen(Col)/nano-hydroxyapatite (nHA) biological composite bone scaffold with double multi-level interface reinforcement

Bone scaffold is expected to possess excellent mechanical and biological properties similar to natural bone tissues. In this study, we aimed to prepare a biomineralized Col and hydroxyapatite composite scaffold consisting of biomimetic bone components and multi-level bionic bone structure to strengthen its mechanical properties. We prepared a Col/nano-hydroxyapatite biological composite scaffold with multi-level structure (from nanofibers to micron bionic bone motif to bionc bone scaffold) of biomimetic bone tissue, and biomineralized the scaffold in simulated body fluid (SBF) preheated to 37 °C. X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and Scanning electron microscope, were used to characterize the biomineralized products. Morphological study confirmed in situ deposition of nHA in the multi-scale hierarchical structure of the biomineralized scaffold. We explored the biomineralization nucleation mechanism of the scaffolds at the atomic level based on the first principles and the mechanisms for growth of mineralized nHA crystal array in its multi-scale structure, and how the double multiscales structure strengthened the mechanical properties of the material. This synthetic bone scaffold, with bionic bone composition and double multi-level interface reinforcement, provides a new strategy for synthesizing bioactive bone scaffolds with enhanced biomechanical properties.

3D printed hydrogel for articular cartilage regeneration

Tissue engineering is a promising strategy for damaged cartilage tissue repair. Three-dimensional (3D) printed hydrogel exhibits great potential in cartilage tissue engineering for fabricating 3D cell culture scaffolds, owing to its similarity to the extracellular matrix (ECM). Numerous hydrogels have been tested for 3D printing in vitro articular cartilage tissues, including natural and synthetic hydrogels that mimic their in vivo counterparts. The advancement of materials science and 3D printing techniques enables a wide range of fabrication strategies that produce cartilage tissues with delicate structures and on multiple scales. Stimuli-responsive hydrogels, which rely on the external environment to transform to a desired structure or dimension, have likewise been widely studied in tissue engineering. This review summarizes the characteristics, functions, and research conducted on 3D printed hydrogels by categorizing cutting-edge hydrogel materials commonly used in cartilage tissue engineering and their complexes. The challenges and application prospects of hydrogels in cartilage tissue engineering are described. Novel composite hydrogels must be investigated to meet the requirements of native articular cartilage in the aspects of structure, scale, mechanical properties, among others. Combining stimuli-responsive hydrogels with biological scaffolds also shows great potential in various applications, including but not limited to articular cartilage, vascularization, and osteochondral repair.

Preparation of a robust silk fibroin scaffold with a reinforced concrete structure constructed with silk nanofibers as the skeleton based on a CaCl2-formic acid solution and freeze-drying method

Regenerated silk fibroin has been widely used in tissue engineering due to its tunable mechanical properties, biocompatibility and degradability, especially in biological scaffolds. In this paper, for the first time, a robust silk fibroin (SF) scaffold with a reinforced concrete structure constructed with silk nanofibers as the skeleton was prepared by combining a CaCl2-formic acid (FA-CaCl2) dissolving system with a freeze-drying method. This method consumes less time and greatly reduces the rate of silk loss, while formic acid can be collected and reused as a solvent during the lyophilization process. Moreover, the SF scaffolds prepared by this method retained the nanofibers of silk, thus preserving the mechanical toughness of the silk nanofibers. On this basis, a reinforced concrete structure with silk nanofibers as the skeleton and amorphous silk as the filler was constructed, which exhibited increased strength and toughness. Effects of preparation conditions (dissolution system, degumming time, silk content) on the mechanical properties and the relationship between structure and mechanical properties of the scaffolds were also studied. Among them, the strength of SF scaffold with degumming time of 10 min, silk content of 20 wt% and directional pores was the best, and its Young's modulus could reach 3.56 MPa. In addition, the scaffolds prepared by this method had good biocompatibility and biodegradability. This study provides a new strategy for manufacturing SF scaffolds and an alternative for the preparation of related silk fibroin materials, which have excellent potential in the field of tissue engineering.

L’implantation de fragments méniscaux autologues enveloppés par du fascia induit la régénération du fibrocartilage en cas de pertes de substance méniscales sévères chez le mouton : étude histologique et biomécanique

IntroductionCurrently, various studies have been reported to regenerate the meniscus tissue in a large defect after partial meniscectomy using biological or synthetic scaffolds with or without fibrochondrocytes. However, the clinical utility of those treatments has not been established as of yet. HypothesisPurposes of this study were to develop a sheep model to evaluate feasibility of this new surgical strategy to treat the irreparable meniscus injury, and to test the hypothesis that implantation of autogenous meniscal fragments wrapped with a fascia sheath may significantly induce fibrocartilage regeneration in a large meniscal defect in the sheep model. Methods and methodsTwenty Suffolk sheep were used. In each animal, an anterior 10-mm width of the right medial meniscus was resected. Then, the animals were divided into the following 2 groups. In Group I, the defect was enveloped with a fascia from the left thigh. In Group II, the resected meniscus fragmented into small pieces was grafted into the defect. Then the defect was enveloped with a fascia. In each group, 5 of 10 sheep were used for histological and biomechanical evaluations, respectively, at 12 weeks after surgery. ResultsIn Group I, the defect was incompletely filled with thin fibrous tissues, while fibrocartilage tissues rarely regenerated in the tissue. In Group II, all defects were completely filled with thick fibrocartilage tissues, which were richly stained with the safranin O staining. Both the gross and histological observation score of Group II was significantly (p=0.0005, p=0.0005) greater than that of Group I. Concerning the cross-sectional area of the regenerated tissue, Group II was significantly (p=0.0002) greater than Group I. In the biomechanical evaluation, the maximal load and the linear stiffness of the meniscus-tibia complex were significantly (p=0.0015, p=0.0283) greater in Group II than in Group I. DiscussionsImplantation of autogenous meniscal fragments wrapped with a fascia sheath significantly induces fibrocartilage regeneration into a large meniscal defect in the sheep model. Level of evidencenot applicable; Controlled Laboratory Study, Experimental in vivo study.

3D Bioprinting for Spinal Cord Injury Repair.

Spinal cord injury (SCI) is considered to be one of the most challenging central nervous system injuries. The poor regeneration of nerve cells and the formation of scar tissue after injury make it difficult to recover the function of the nervous system. With the development of tissue engineering, three-dimensional (3D) bioprinting has attracted extensive attention because it can accurately print complex structures. At the same time, the technology of blending and printing cells and related cytokines has gradually been matured. Using this technology, complex biological scaffolds with accurate cell localization can be manufactured. Therefore, this technology has a certain potential in the repair of the nervous system, especially the spinal cord. So far, this review focuses on the progress of tissue engineering of the spinal cord, landmark 3D bioprinting methods, and landmark 3D bioprinting applications of the spinal cord in recent years.

Pullulan-Collagen hydrogel wound dressing promotes dermal remodelling and wound healing compared to commercially available collagen dressings.

Biological scaffolds such as hydrogels provide an ideal, physio‐mimetic of native extracellular matrix (ECM) that can improve wound healing outcomes after cutaneous injury. While most studies have focused on the benefits of hydrogels in accelerating wound healing, there are minimal data directly comparing different hydrogel material compositions. In this study, we utilized a splinted excisional wound model that recapitulates human‐like wound healing in mice and treated wounds with three different collagen hydrogel dressings. We assessed the feasibility of applying each dressing and performed histologic and histopathologic analysis on the explanted scar tissues to assess variations in collagen architecture and alignment, as well as the tissue response. Our data indicate that the material properties of hydrogel dressings can significantly influence healing time, cellular response, and resulting architecture of healed scars. Specifically, our pullulan‐collagen hydrogel dressing accelerated wound closure and promoted healed tissue with less dense, more randomly aligned, and shorter collagen fibres. Further understanding of how hydrogel properties affect the healing and resulting scar architecture of wounds may lead to novel insights and further optimization of the material properties of wound dressings.

Production Protocol Standardisation, Macroscopic and Histological Evaluation, and Growth Factor Quantification of Canine Leukocyte-and Platelet-Rich Fibrin Membranes.

Leukocyte-Platelet-Rich Fibrin (L-PRF) is a second generation of platelet concentrates; it was widely used, as an autologous platelet-based wound sealant and hemostatic agent in surgical wound healing. L-PRF clot or membrane is a solid fibrin-based biomaterial, with a specific 3D distribution of the leukocytes and platelet aggregates. This biological scaffold releases growth factors (i.e., TGF- β1, PDGF-AB, VEGF) and matrix proteins (fibronectin, vitronectin and thrombospondin-1) during the healing process after the application. To the Authors' knowledge both in human and veterinary medicine a single standardised protocol was not reported. This prospective study aimed to apply Crisci's L-PRF protocol (which is characterised by 30” of acceleration, 2' at 2,700 rpm, 4' at 2,400 rpm, 3' at 3,000 rpm, and 36” of deceleration and arrest) sin canine species, evaluate macroscopically and histologically the L-PRF membranes obtained by using Wound Box to standardise the L-PRF protocol in dogs and to evaluate the clinical feasibility of using L-PRF membranes by quantitative in vitro analysis of growth factors over 7 days. One hundred twenty-eight dogs in good general condition with no history of recent NSAIDs intake (15 days of washout) and/or any medication or disease related to coagulation process met inclusion criteria and therefore were enrolled. We obtained 172 membrane L-PRF membranes by 86 dogs: half of them underwent macroscopic and histological analysis, the other 86 underwent ELISA analysis. The Wound Box gave a membrane of mean (±SD) length (cm), width (cm) and weight (g) of 1.97 (±0.89), 0.95 (±0.36), 0.46 (±0.20) respectively. Histology analysis confirmed a well-defined histoarchitecture with five layers reproducing density and distribution of blood cells in this biomaterial. Finally, the ELISA assay performed with 22 L-PRF membranes showed a peak in growth factors at 6 h after membrane production, followed by a decrease in release at 24 and 72 h and a second peak in release at 168 h after production. Statistical analysis of demographic variables (age, sex, and body condition score BCS) and the average of growth factors determined by the ELISA assay did not reveal statistical significance, except for the BCS factor compared with the production of VEGF. Our data confirm the effectiveness of this protocol and of Wound Box to produce L-PRF membranes in dogs.

Tailorable and predictable mechanical responses of additive manufactured TPMS lattices with graded structures

In this study, graded Gyroid-type TPMS graded lattice structures were designed and manufactured by laser powder bed fusion, showing tailorable and predictable mechanical responses, such as Young's modulus, yield strength, and multi-platform stress-strain curves. The strong regularity of the mechanical response makes it possible to predict, while the difference in gradient degree makes the prediction difficult. Revised mathematical equations were modelled to accurately predict the mechanical responses of graded lattice structures. Insights and equation models can be used as guidance for the design of graded lightweight structures and biological bone scaffolds.

Functional biomaterials for tendon/ligament repair and regeneration.

With an increase in life expectancy and the popularity of high-intensity exercise, the frequency of tendon and ligament injuries has also increased. Owing to the specificity of its tissue, the rapid restoration of injured tendons and ligaments is challenging for treatment. This review summarizes the latest progress in cells, biomaterials, active molecules and construction technology in treating tendon/ligament injuries. The characteristics of supports made of different materials and the development and application of different manufacturing methods are discussed. The development of natural polymers, synthetic polymers and composite materials has boosted the use of scaffolds. In addition, the development of electrospinning and hydrogel technology has diversified the production and treatment of materials. First, this article briefly introduces the structure, function and biological characteristics of tendons/ligaments. Then, it summarizes the advantages and disadvantages of different materials, such as natural polymer scaffolds, synthetic polymer scaffolds, composite scaffolds and extracellular matrix (ECM)-derived biological scaffolds, in the application of tendon/ligament regeneration. We then discuss the latest applications of electrospun fiber scaffolds and hydrogels in regeneration engineering. Finally, we discuss the current problems and future directions in the development of biomaterials for restoring damaged tendons and ligaments.

A biomimetic and bioactive scaffold with intelligently pulsatile teriparatide delivery for local and systemic osteoporosis regeneration.

Osteoporosis is one of the most disabling consequences of aging, osteoporotic fractures and higher risk of the subsequent fractures leading to substantial disability and deaths, indicating both local fractures healing and the early anti-osteoporosis therapy are of great significance. Teriparatide is strong bone formation promoter effective in treating osteoporosis, while side effects limit clinical applications. Traditional drug delivery is lack of sensitive and short-term release, finding a new non-invasive and easily controllable drug delivery to not only repair the local fractures but also improve total bone mass has remained a great challenge. Thus, bioinspired by the natural bone components, we develop appropriate interactions between inorganic biological scaffolds and organic drug molecules, achieving both loaded with the teriparatide in the scaffold and capable of releasing on demand. Herein, biomimetic bone microstructure of mesoporous bioglass, a near-infrared ray triggered switch, thermosensitive liposomes based on a valve, and polydopamine coated as a heater is developed rationally for osteoporotic bone regeneration. Teriparatide is pulsatile released from intelligent delivery, not only rejuvenating osteoporotic bone defect, but also presenting strong systemic anti-osteoporosis therapy. This biomimetic bone carrying novel drug delivery platform is well worth expecting to be a new promising strategy and clinically commercialized to help patients survive from the osteoporotic fracture.

Ultrafast Collective Excited-State Dynamics of a Virus-Supported Fluorophore Antenna.

Radiation brightening was recently observed in a multifluorophore-conjugated brome mosaic virus (BMV) particle at room temperature under pulsed excitation. On the basis of its nonlinear dependence on the number of chromophores, the origins of the phenomenon were attributed to a collective relaxation. However, the mechanism remains unknown. We present ultrafast transient absorption and fluorescence spectroscopic studies which shed new light on the collective nature of the relaxation dynamics in such radiation-brightened, multifluorophore particles. Our findings indicate that the emission dynamics is consistent with a superradiance mechanism. The ratio between the rates of competing radiative and nonradiative relaxation pathways depends on the number of chromophores per virus. The findings suggest that small icosahedral virus shells provide a unique biological scaffold for developing nonclassical, deep subwavelength light sources and may open new avenues for the development of photonic probes for medical imaging applications.

Somethings About Biological Prostheses

Finite element models of the female biofidel were developed using a specific combination of segmentation with computed tomography and solid modeling tools capable of representing bone physiology and structural behavior. This biofidel finite element (FEM) model is used to evaluate the change in the physiological distribution of stress in the femoral prosthesis and to evaluate the new design criteria for biopsy. Biomimetics, biomechanics, and tissue engineering are three multidisciplinary fields that have been considered in this research to achieve the goal of improving the reliability of prosthetic implants. The authors took these studies to gather the untapped potential of such advanced materials and design technologies by developing finite models of Biofidel elements capable of correctly mimicking the biomechanical behavior of the femur. The new remodeling of the tetrahedral elements was performed in 3Matic looking for the congruence of the node at the bone-implant interfaces, where the material was defined for the new configuration of the finite elements. The evaluation of the mechanical properties was made taking into account the mechanical characteristics of the cortical and trabecular bone. For biomechanical integration of the implant, a custom material with an improved combination of strength and rigidity that matches the bone should be used. This greater biomechanical compatibility will avoid weakening the implant and increase lifespan, avoiding additional surgery for revision and allowing good biological integration (bone growth). Innovative biomimetic materials for tissue engineering based on hydrophilic polymers were developed by our research group and presented attractive physical, biological, and mechanical properties for biomedical applications. For use with metal prostheses, the authors have developed a hybrid biocompatible material, extremely biocompatible, based on hydrophilic chemicals and hydroxy-ethyl-methacrylate type. The structural metal composition of the new prostheses will be made of titanium alloys using additive technology based on melting thin layers of titanium powder (about 50 microns) on each other until the desired component is obtained (sandwich method). Then, the biomaterial and osteoconductive nanostructured material developed in our previous studies can cover the titanium structural prosthetic skeleton. These hybrid biological prostheses, which are made using synthetic materials capable of inducing the growth of biological networks and structural steel scaffolding, may favor the emergence of new classes of orthopedic hybrids in the medical field. The new hybrid bio-prosthesis could drastically reduce protection against stress while providing an advantageous improvement in the life of the prosthesis compared to traditional solutions. Recovering optimal joint functionality will improve the patient's quality of life, which perceives a significant reduction in the risk of the new surgery. The requirement to predict potential structural changes that could be induced by improper use of biologically compatible prostheses in bone structure and morphology has forced our studies to evaluate fictitious models that could be considered for efficient bone distribution and orthotropic behavior.

Lateral collagen meniscus implant (CMI): techniques and outcomes-a narrative review.

The menisci increase the stability of the tibio-femoral joint, distribute axial load, absorb shock, and provide nutrition and lubrification to the knee articular cartilage. Therefore, is it clear the importance of the meniscus on the overall knee function and the need to preserve it during arthroscopic surgery. However, according to many registry databases, meniscectomy is still the most performed meniscus surgery. In a percentage of patients, knee pain and swelling, as well as bone edema on the tibial plateau, could follow meniscus resection; this constellation of symptoms is known as "post-meniscectomy syndrome". If this syndrome is not promptly managed, a rapid worsening of the symptoms and develop of knee osteoarthritis could be expected. While dealing with such condition, the clinician must perform first an accurate clinical examination and a full radiological evaluation. If the patient is candidate for surgery, the replacement of the resected tissue should be performed: a meniscus allograft should be implanted in case of previous total meniscectomy or a meniscus scaffold if the patients has an history of a previous partial resection. The present article represents a comprehensive review of the literature and aims to discuss basic science, preoperative planning and evaluation, indication, surgical technique, and outcomes of the lateral collagen meniscus implant (CMI), a biologic scaffold aimed at replacing partial meniscal defects.

Natural Scaffolds Used for Liver Regeneration: A Narrative Update.

Annually chronic liver diseases cause two million death worldwide. Although liver transplantation (LT) is still considered the best therapeutic option, the limited number of donated livers and lifelong side effects of LT has led researchers to seek alternative therapies. Tissue engineering (TE) as a promising method is considered for liver repair and regeneration. TE uses natural or synthetic scaffolds, functional somatic cells, multipotent stem cells, and growth factors to develop new organs. Biological scaffolds are notable in TE because of their capacity to mimic extracellular matrices, biodegradability, and biocompatibility. Moreover, natural scaffolds are classified based on their source and function in three separate groups. Hemostat-based scaffolds as the first group were reviewed for their application in coagulation in liver injury or surgery. Furthermore, recent studies showed improvement in the function of biological hydrogels in liver regeneration and vascularity. In addition, different applications of natural scaffolds were discussed and compared with synthetic scaffolds. Finally, we focused on the efforts to improve the performance of decellularized extracellular matrixes for liver implantation.

Osteogenic differentiation of human dental pulp stem cells in decellularised adipose tissue solid foams.

3D cell culture systems based on biological scaffold materials obtainable from both animal and human tissues constitute very interesting tools for cell therapy and personalised medicine applications. The white adipose tissue (AT) extracellular matrix (ECM) is a very promising biomaterial for tissue engineering due to its easy accessibility, malleability and proven biological activity. In the present study, human dental pulp stem cells (hDPSCs) were combined in vitro with ECM scaffolds from porcine and human decellularised adipose tissues (pDAT, hDAT) processed as 3D solid foams, to investigate their effects on the osteogenic differentiation capacity and bone matrix production of hDPSCs, compared to single-protein-based 3D solid foams of collagen type I and conventional 2D tissue-culture-treated polystyrene plates. pDAT solid foams supported the osteogenic differentiation of hDPSCs to similar levels to collagen type I, as assessed by alkaline phosphatase and alizarin red stainings, reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and osteocalcin/bone gamma-carboxyglutamate protein (BGLAP) immunostaining. Interestingly, hDAT solid foams showed a markedly lower capacity to sustain hDPSC osteogenic differentiation and matrix calcification and a higher capacity to support adipogenesis, as assessed by RT-qPCR and oil red O staining. White ATs from both human and porcine origins are relatively abundant and available sources of raw material to obtain high quality ECM-derived biomedical products. These biomaterials could have promising applications in tissue engineering and personalised clinical therapy for the healing and regeneration of lesions involving not only a loss of calcified bone but also its associated soft non-calcified tissues.