FIGURE 7 - uploaded by Kristyna Kekulova
Content may be subject to copyright.
Representative images of the longitudinal sections of the spinal cord lesion in (A,E) control and at 8 weeks after subacute injection of (B,F) HA-PH-RGD, (C,G) HA-PH-RGD/F and (D,H) HA-PH-RGD/F hydrogel combined with hWJ-MSCs. Staining for (A-D) macrophages (ED1, green) and M2 macrophages (CD206, red), (E-H) oligodendrocytes (MOSP, red) and (A-H) DAPI (blue). The dotted lines in (A,E) outline the border of the tissue (T) and the lesion area (L). Other images are taken from the center of the lesion. Scale bar: 50 lm.
Source publication
Hydrogel scaffolds which bridge the lesion, together with stem cell therapy represent a promising approach for spinal cord injury (SCI) repair. In this study, a hydroxyphenyl derivative of hyaluronic acid (HA-PH) was modified with the integrin binding peptide RGD, and enzymatically crosslinked to obtain a soft injectable hydrogel. Moreover, additio...
Contexts in source publication
Context 1
... staining, specific for microglia/macrophages, combined with CD206 staining specific for M2 macrophages confirmed the migration of both M1 and M2 macrophages into the hydrogel treated lesion, however, no quantification was performed to detect the M1/M2 ratio [ Fig. 7(A-D)]. Oligodendrocytes were detected in the area of hydrogel treated lesions, but not in the control lesion [ Fig. ...
Context 2
... combined with CD206 staining specific for M2 macrophages confirmed the migration of both M1 and M2 macrophages into the hydrogel treated lesion, however, no quantification was performed to detect the M1/M2 ratio [ Fig. 7(A-D)]. Oligodendrocytes were detected in the area of hydrogel treated lesions, but not in the control lesion [ Fig. ...
Context 3
... effect of the hydrogel treatment on the locomotor functions, such as knee and ankle angles and hind limb retraction and protraction (distance on x-axis of metatarsophalangeal joint in relation to iliac crest), was measured using the TSE Motion 8.5.11. No statistical differences between the control and hydrogel treated animals was found at 2, 5 and 8 weeks (Supporting Information Fig. S7). ...
Similar publications
Introduction: Cartilage injury is the most common injury among orthopedic diseases. The predominant treatment for this condition is cartilage transplantation. Therefore, production of cartilage for treatment is an important strategy in regenerative medicine of cartilage to provide surgeons with an additional option for treatment of cartilage defect...
A challenge in regenerative medicine is governed by the need to have control over the fate of stem cells that is regulated by the physical and chemical microenvironment in vitro and in vivo. The differentiation of the stem cells into specific lineages is commonly guided by use of specific culture media. For the first time, we demonstrate that human...
The development of mechanically functional cartilage and bone tissue constructs of clinically relevant size, as well as their integration with native tissues, remain important challenges for regenerative medicine. The objective of this study was to assess adult human mesenchymal stem cells (MSC) in large, three dimensionally woven poly(epsilon-capr...
Additive manufacturing (AM) has shown promise in designing 3D scaffold for regenerative medicine. However, many synthetic biomaterials used for AM are bioinert. Here, we report synthesis of bioactive nanocomposites from a poly(ethylene oxide terephthalate) (PEOT)/poly(butylene terephthalate) (PBT) (PEOT/PBT) copolymer and 2D nanosilicates for fabri...
Citations
... Other studies use polymeric blends with hyaluronic acid to improve the gel's stability and slow its degradation, as reported using gelatin [106] and glycol chitosan [102]. Blending with hyaluronic acid was also used to promote cell adhesion, as reported for fbrinogen with hydroxyphenyl-modifed hyaluronic acid to obtain stem cell adhesion [107]. Adhesive properties were also obtained using gelatin blended with tyramine-modifed hyaluronic acid [105]. ...
... Enzymatical crosslinking can also obtain injectable hyaluronic-based hydrogels by forming hydroxyphenylmodifed hyaluronic acid's enzymatically induced soft hydrogel when combined with fbrinogen [107]. Another study reported the enzymatic crosslinking of tyraminemodifed hyaluronic acid and gelatin as the resulting phenolic group reacted with the peroxidase enzyme to form the hydrogel [105]. ...
... In vivo evaluation of a partial defect in the spinal cord indicated the prospect of using this hydrogel system for tissue regeneration. Besides the capability to encapsulate stem cells, the hydrogel covers the injured cavity and promotes axonal sprouting and vascularization [107]. Te self-healing hydrogel of hyaluronic acid and methylcellulose polymers was developed and evaluated for spinal cord tissue repair; the produced hydrogel exhibited thixotropic rheological behavior, explaining its good injectability combined with the thermal gelation efect of methylcellulose that suggested the potential of its investigation for sustained delivery applications, besides that, the produced hydrogel system exhibited no cell adhesion, biodegradability, and biocompatibility inside the intrathecal space [54]. ...
The characteristics of injectable hydrogels make them a prime contender for various biomedical applications. Hyaluronic acid is an essential component of the matrix surrounding the cells; moreover, hyaluronic acid’s structural and biochemical characteristics entice researchers to develop injectable hydrogels for various applications. However, due to its poor mechanical properties, several strategies are used to produce injectable hyaluronic acid hydrogel. This review summarizes published studies on the production of injectable hydrogels based on hyaluronic acid polysaccharide polymers and the biomedical field’s applications for these hydrogel systems. Hyaluronic acid-based hydrogels are divided into two categories based on their injectability mechanisms: in situ-forming injectable hydrogels and shear-thinning injectable hydrogels. Many crosslinking methods are used to create injectable hydrogels; chemical crosslinking techniques are the most frequently investigated technique. Hybrid injectable hydrogel systems are widely investigated by blending hyaluronic acid with other polymers or nanoparticulate systems. Injectable hyaluronic acid hydrogels were thoroughly investigated and proven to demonstrate potential in various medical fields, including delivering drugs and cells, tissue repair, and wound dressings.
... Heparin hydrogel microwells have been developed for primary hepatocyte cultivation, testing various surface modifications to enhance hepatic phenotype maintenance, highlighting the benefits of all-heparin gel microwells for liver tissue engineering [116]. Injectable hyaluronic acid-derivative hydrogels, modified with RGD and combined with fibrinogen, have been tested in spinal cord injury repair, facilitating cell adhesion and proliferation for neural tissue engineering [117]. Lastly, interpenetrating network hydrogels of hyaluronic acid and fibrin, prepared in situ, enhance mechanical properties and cell proliferation, presenting a promising scaffold for extracellular matrix-based tissue regeneration [118]. ...
This manuscript covers the latest advancements and persisting challenges in the domain of tissue engineering, with a focus on the development and engineering of hydrogel scaffolds. It highlights the critical role of these scaffolds in emulating the native tissue environment, thereby providing a supportive matrix for cell growth, tissue integration, and reducing adverse reactions. Despite significant progress, this manuscript emphasizes the ongoing struggle to achieve an optimal balance between biocompatibility, biodegradability, and mechanical stability, crucial for clinical success. It also explores the integration of cutting-edge technologies like 3D bioprinting and biofabrication in constructing complex tissue structures, alongside innovative materials and techniques aimed at enhancing tissue growth and functionality. Through a detailed examination of these efforts, the manuscript sheds light on the potential of hydrogels in advancing regenerative medicine and the necessity for multidisciplinary collaboration to navigate the challenges ahead.
... Nevertheless, HA materials exhibit disadvantages such as poor cell adhesion 38 . To overcome these drawbacks, HA can be modified, such as with the integrin-binding peptide arginine-glycine-aspartic acid (RGD) 39 , to enhance cell adhesion and migration to implants. Moreover, 3D hydrogel scaffolds prepared by blending HA with gelatin are effective in promoting endogenous neural stem cell (NSC) migration and neurogenesis 40 . ...
As one of the most intractable neurological diseases, spinal cord injury (SCI) often leads to permanent neurological impairment in patients. Unfortunately, due to the complex pathological mechanisms and unique postinjury microenvironment, there is currently no way to completely repair the injured spinal cord. In recent years, with the rapid development of tissue engineering technology, the combination of biomaterials and medicine has provided a new idea for treating SCI. Here, we systematically summarize representative biomaterials, including natural, synthetic, nano, and hybrid materials, and their applications in SCI treatment. In addition, we describe several state-of-the-art fabrication techniques for tissue engineering. Importantly, we provide novel insights for the use of biomaterial-based therapeutic strategies to reduce secondary damage and promote repair. Finally, we discuss several biomaterial clinical studies. This review aims to provide a reference and new insights for the future exploration of spinal cord regeneration strategies.
... These are extensively hydrated polymer constructs, and their design and characteristics can be customized to meet specific requirements [7][8][9][10][11]. Prior research indicates that various hydrogels, such as polysaccharides [12][13][14], polyacids [15,16], polymethacrylates [17,18], fibrous hydrogels [19][20][21], and other self-assembled hydrogels [22][23][24], can be designed to mimic the structure of the absent extracellular matrix (ECM) in tissue injuries, thereby promoting internal cell growth and differentiation. Dynamic network hydrogels represent an advanced subset of these materials. ...
Osteoporosis and degenerative endocrine diseases are some of the major causes of disability in the elderly. The feedback loop in the endocrine system works to control the release of hormones and maintain the homeostasis of metabolism, thereby regulating the function of target organs. The breakdown of this feedback loop results in various endocrine and metabolic disorders, such as osteoporosis, type II diabetes, hyperlipidemia, etc. The direct regulation of redox homeostasis is one of the most attractive strategies to redress the imbalance of the feedback loop. The biophysical regulation of redox homeostasis can be achieved through engineered dynamic hydrogel niches, with which cellular mechanics and redox homeostasis are intrinsically connected. Mechanotransduction-dependent redox signaling is initiated by cell surface protein assemblies, cadherins for cell–cell junctions, and integrins for cell–ECM interactions. In this review, we focused on the biophysical regulation of redox homeostasis via the tunable cell–ECM interactions in the engineered dynamic hydrogel niches. We elucidate processes from the rational design of the hydrogel matrix to the mechano-signaling initiation and then to the redox response of the encapsulated cells. We also gave a comprehensive summary of the current biomedical applications of this strategy in several degenerative endocrine disease models.
... According to a behavioral and electrophysiological analysis, 3D-printed collagen/silk fibrin scaffolds carrying umbilical secretomes of MSCs improved hindlimb locomotor functionality [183]. Wharton's jelly-derived MSCs applied with integrin-binding peptide RGD bridged the lesion cavity, supported vascularization, upregulated related gene expressions and increased axonal sprouting into the lesion [184]. The transplantation of human umbilical cord MSCs seeded in collagen scaffolds also reduced scar formation and promoted functional recovery in chronic SCI [183,185]. ...
Spinal cord injury (SCI) is a catastrophic condition associated with significant neurological deficit and social and financial burdens. It is currently being managed symptomatically, with no real therapeutic strategies available. In recent years, a number of innovative regenerative strategies have emerged and have been continuously investigated in preclinical research and clinical trials. In the near future, several more are expected to come down the translational pipeline. Among ongoing and completed trials are those reporting the use of biomaterial scaffolds. The advancements in biomaterial technology, combined with stem cell therapy or other regenerative therapy, can now accelerate the progress of promising novel therapeutic strategies from bench to bedside. Various types of approaches to regeneration therapy for SCI have been combined with the use of supportive biomaterial scaffolds as a drug and cell delivery system to facilitate favorable cell–material interactions and the supportive effect of neuroprotection. In this review, we summarize some of the most recent insights of preclinical and clinical studies using biomaterial scaffolds in regenerative therapy for SCI and summarized the biomaterial strategies for treatment with simplified results data. One hundred and sixty-eight articles were selected in the present review, in which we focused on biomaterial scaffolds. We conducted our search of articles using PubMed and Medline, a medical database. We used a combination of “Spinal cord injury” and [“Biomaterial”, or “Scaffold”] as search terms and searched articles published up until 30 April 2022. Successful future therapies will require these biomaterial scaffolds and other synergistic approaches to address the persistent barriers to regeneration, including glial scarring, the loss of a structural framework, and biocompatibility. This database could serve as a benchmark to progress in future clinical trials for SCI using biomaterial scaffolds.
... Natural-derived biomaterials provide structures similar to the natural ECM, which may favor the integration of the implanted scaffold with the host tissue [283]. Natural biomaterials such as collagen [284], hyaluronic acid [285], agarose [286], alginate [287], and gellan gum [288,289] have been showing some promising results for SCI repair. ...
Spinal cord injury (SCI) is a disabling condition that disrupts motor, sensory, and autonomic functions. Despite extensive research in the last decades, SCI continues to be a global health priority affecting thousands of individuals every year. The lack of effective therapeutic strategies for patients with SCI reflects its complex pathophysiology that leads to the point of no return in its function repair and regeneration capacity. Recently, however, several studies started to uncover the intricate network of mechanisms involved in SCI leading to the development of new therapeutic approaches. In this work, we present a detailed description of the physiology and anatomy of the spinal cord and the pathophysiology of SCI. Additionally, we provide an overview of different molecular strategies that demonstrate promising potential in the modulation of the secondary injury events that promote neuroprotection or neuroregeneration. We also briefly discuss other emerging therapies, including cell-based therapies, biomaterials, and epidural electric stimulation. A successful therapy might target different pathologic events to control the progression of secondary damage of SCI and promote regeneration leading to functional recovery.
... Secondly, it can form in situ gelling system. Reports have already demonstrated the in situ hydrogel forming ability of HA (Zaviskova et al., 2018). HA-SH has been utilized to prepare hydrogels with other chemicals through chemical reactions between the functional groups. ...
Suitable bone grafts are commonly required to achieve successful bone regeneration, wherein much effort has been spent to optimize their osteogenesis. Increasing evidence has demonstrated that reducing the levels of TNF-α can enhance bone regeneration at the injury site. Notoginsenoside R1 (NGR1) has been extensively studied in the field of anti-inflammation and regenerative medicine. Nanosized hydroxyapatite (nHAp) possesses excellent biocompatibility and osteoconductivity. In this study, we fabricated a thermoresponsive, injectable hyaluronic acid/nHAp (HA/nHAp) composite hydrogel incorporated with NGR1 to promote bone regeneration. Furthermore, NGR1-HA/nHAp hydrogel could enhance bone regeneration than those of HA and HA/nHAp hydrogels, profited by the underlying osteoblastic mechanism that NGR1 could facilitate activation of the MAPK/ERK signaling pathway and down-regulate the expression of TNF-α, ultimately upregulated expression of osteogenic genes. In summary, the NGR1-HA/nHAp composite hydrogel with controlled inflammation, and excellent osteogenic effect, will have great potential for use in bone regeneration applications.
... Natural HA does not affect cell adhesion or gel formation. Hence, it is necessary to chemically alter the functional groups of HA, adjusting their physical, chemical, or biological properties according to special requirements of specific applications (Zaviskova et al., 2018). In the absence of chemical cross-linking agents, hydrogels are formed by Schiff bases between the amino group of ethylene glycol-chitosan and the aldehyde group of oxidized hyaluronate. ...
The rapid development of tissue engineering makes it an effective strategy for repairing cartilage defects. The significant advantages of injectable hydrogels for cartilage injury include the properties of natural extracellular matrix (ECM), good biocompatibility, and strong plasticity to adapt to irregular cartilage defect surfaces. These inherent properties make injectable hydrogels a promising tool for cartilage tissue engineering. This paper reviews the research progress on advanced injectable hydrogels. The cross-linking method and structure of injectable hydrogels are thoroughly discussed. Furthermore, polymers, cells, and stimulators commonly used in the preparation of injectable hydrogels are thoroughly reviewed. Finally, we summarize the research progress of the latest advanced hydrogels for cartilage repair and the future challenges for injectable hydrogels.
... MSCs encapsulated in RGD-hydrogel could expedite wound healing via enhancing angiogenesis and suppressing local proinflammatory cytokines [18]. Furthermore, a subacute injection of RGD-hydrogel combined with MSCs could further promote axonal ingrowth into the lesion of spinal cord injury [19]. For the treatment of respiratory diseases, the intratracheal administration of hydrogel combined with fibroblast growth factor and interleukin-10 (IL-10) could alleviate monocutarine-induced pulmonary hypertension and bleomycin-induced pulmonary fibrosis, respectively [20,21]. ...
Mesenchymal stem cells (MSCs) have promising potential in the treatment of various diseases, such as the therapeutic effect of bone marrow-derived MSCs for phosgene-induced acute lung injury (P-ALI). However, MSC-related therapeutics are limited due to poor cell survival, requiring appropriate MSC delivery systems to maximise therapeutic capacity. Biomaterial RGD-hydrogel is a potential cell delivery vehicle as it can mimic the natural extracellular matrix and provide cell adhesion support. The application of RGD-hydrogel in the MSC treatment of respiratory diseases is scarce. This study reports that RGD-hydrogel has good biocompatibility and can increase the secretion of Angiopoietin-1, hepatocyte growth factor, epidermal growth factor, vascular endothelial cell growth factor, and interleukin-10 in vitro MSCs. The hydrogel-encapsulated MSCs could further alleviate P-ALI and show better cell survival in vivo. Overall, RGD-hydrogel could improve the MSC treatment of P-ALI by modulating cell survival and reparative activities. It is exciting to see more and more ways to unlock the therapeutic potential of MSCs.
... IKVAV-HA implants inserted into brain defects were invaded by blood vessels, glial cells and axons to promote new tissue formation by 6 weeks of implantation. Integrin binding RGD peptide attached to hydroxyphenyl-modified HA has also improved cell-binding properties and has been applied in spinal cord repair [72]. ...
The aim of this study was to illustrate recent developments in neural repair utilizing hyaluronan as a carrier of olfactory bulb stem cells and in new bioscaffolds to promote neural repair. Hyaluronan interacts with brain hyalectan proteoglycans in protective structures around neurons in perineuronal nets, which also have roles in the synaptic plasticity and development of neuronal cognitive properties. Specialist stem cell niches termed fractones located in the sub-ventricular and sub-granular regions of the dentate gyrus of the hippocampus migrate to the olfactory bulb, which acts as a reserve of neuroprogenitor cells in the adult brain. The extracellular matrix associated with the fractone stem cell niche contains hyaluronan, perlecan and laminin α5, which regulate the quiescent recycling of stem cells and also provide a means of escaping to undergo the proliferation and differentiation to a pluripotent migratory progenitor cell type that can participate in repair processes in neural tissues. Significant improvement in the repair of spinal cord injury and brain trauma has been reported using this approach. FGF-2 sequestered by perlecan in the neuroprogenitor niche environment aids in these processes. Therapeutic procedures have been developed using olfactory ensheathing stem cells and hyaluronan as a carrier to promote neural repair processes. Now that recombinant perlecan domain I and domain V are available, strategies may also be expected in the near future using these to further promote neural repair strategies.
