Hyaluronic Acid Scaffold Research Articles

Chemical Modifications in Hyaluronic Acid-Based Electrospun Scaffolds.

Hyaluronic acid (HA) is a natural, non-sulfated glycosaminoglycan (GAG) present in ECM. It is involved in different biological functions with appealing properties in cosmetics and pharmaceutical preparations as well as in tissue engineering. Generally, HA has been electrospun in blends with natural or synthetic polymers to produce fibers having diameters in the order of nano and micro-scale whose pores can host cells able to regenerate damaged tissues. In the last decade, a rich literature on electrospun HA-based materials arose. Chemical modifications were generally introduced in HA scaffolds to favour crosslinking or conjugation with bioactive molecules. Considering the high solubility of HA in water, HA-based electrospun scaffolds are cross-linked to increase the stability in biological fluids. Crosslinking is necessary also to avoid the release of HA from the hybrid scaffold when implanted in-vivo. Furthermore, to endow the HA based scaffolds with new chemical or biological properties, conjugation of bioactive molecules to HA was widely reported. Herein, we review the existing research classifying chemical modifications on HA and HA-based electrospun fibers into three categories: i) in-situ crosslinking of electrospun HA-based scaffolds ii) off-site crosslinking of electrospun HA-based scaffolds; iii) conjugation of biofunctional molecules to HA with focus on peptides.

Development of a Cissus quadrangularis-Doped Extracellular Matrix and a Hyaluronic Acid-Incorporated Scaffold for Periodontal Regeneration: An In Vitro Study.

The study aimed to analyze whether adding Cissus quadrangularis (CQ) extract and the extracellular matrix of ovine tendon (TENDON) increases the regenerative potential of mesenchymal stem cells produced in hyaluronic acid (HA) scaffolds for tenogenesis. Fifty grams of powdered CQ was mixed with 250 mL of ethanol to prepare the extract. Two grams of hyaluronic acid powder was added to 100 mL of distilled water to make the HA solution. The ovine tendon was decellularized using a mixture of 10% phosphate-buffered saline (PBS), sodium dodecyl sulfate (SDS), and Triton-X. The hydrogel samples were prepared by mixing the extracellular matrix of tendon, HA, and CQ, after which they were divided into study groups such as HA, HA + CQ, HA + TENDON, and HA + CQ + TENDON. Scanning electron microscopy (SEM) analysis, swelling analysis, differentiation analysis, compression test, compatibility assay, and tenogenesis assay were later conducted. The morphology of the samples was analyzed using SEM. Low levels of swelling of the hydrogels were observed. Cells were found to be viable and showed good differentiation and tenogenesis. Optimal compression levels were observed, and the properties of the prepared hydrogels were satisfactory. The results suggest that the addition of CQ considerably increases the tenogenic potential of the extracellular matrix/HA scaffold. Hence, it can be used as a regenerative material for periodontal tissue regeneration.

Initial IL-10 production dominates the therapy of mesenchymal stem cell scaffold in spinal cord injury.

Rationale: Spinal cord injury (SCI) is an acute damage to the central nervous system that results in severe morbidity and permanent disability. Locally implanted scaffold systems with immobilized mesenchymal stem cells (MSCs) have been widely proven to promote locomotor function recovery in SCI rats; however, the underlying mechanism remains elusive. Methods and Results: In this study, we constructed a hyaluronic acid scaffold system (HA-MSC) to accelerate the adhesive growth of human MSCs and prolong their survival time in SCI rat lesions. MSCs regulate local immune responses by upregulating the expression of anti-inflammatory cytokines. Interestingly, the dramatically increased, but transient expression of interleukin 10 (IL-10) is found to be secreted by MSCs in the first week. Blocking the function of the initially produced IL-10 by the antibody completely abolished the neurological and behavioral recovery of SCI rats, indicating a core role of IL-10 in SCI therapy with HA-MSC implantation. Transcriptome analyses indicated that IL-10 selectively promotes the migration and cytokine secretion-associated programs of MSCs, which in turn helps MSCs exert their anti-inflammatory therapeutic effects. Conclusion: Our findings highlight a novel role of IL-10 in regulating MSC migration and cytokine secretion-associated programs, and determine the vital role of IL-10 in the domination of MSC treatment for spinal cord repair.

Non-neotissue constituents as underestimated confounders in the assessment of tissue engineered constructs by near-infrared spectroscopy

Non-destructive assessments are required for the quality control of tissue-engineered constructs and the optimization of the tissue culture process. Near-infrared (NIR) spectroscopy coupled with machine learning (ML) provides a promising approach for such assessment. However, due to its nonspecific nature, each spectrum incorporates information on both neotissue and non-neotissue constituents of the construct; the effect of these constituents on the NIR-based assessments of tissue-engineered constructs has been overlooked in previous studies. This study investigates the effect of scaffolds, growth factors, and buffers on NIR-based assessments of tissue-engineered constructs. To determine if these non-neotissue constituents have a measurable effect on the NIR spectra of the constructs that can introduce bias in their assessment, nine ML algorithms were evaluated in classifying the NIR spectra of engineered cartilage according to the scaffold used to prepare the constructs, the growth factors added to the culture media, and the buffers used for storing the constructs. The effect of controlling for these constituents was also evaluated using controlled and uncontrolled NIR-based ML models for predicting tissue maturity as an example of neotissue-related properties of interest. Samples used in this study were prepared using norbornene-modified hyaluronic acid scaffolds with or without the conjugation of an N-cadherin mimetic peptide. Selected samples were supplemented with transforming growth factor-beta1 or bone morphogenetic protein-9 growth factor. Some samples were frozen in cell lysis buffer, while the remaining samples were frozen in PBS until required for NIR analysis. The ML models for classifying the spectra of the constructs according to the four constituents exhibited high to fair performances, with F1 scores ranging from 0.9 to 0.52. Moreover, controlling for the four constituents significantly improved the performance of the models for predicting tissue maturity, with improvement in F1 scores ranging from 0.09 to 0.77. In conclusion, non-neotissue constituents have measurable effects on the NIR spectra of tissue-engineered constructs that can be detected by ML algorithms and introduce bias in the assessment of the constructs by NIR spectroscopy. Therefore, controlling for these constituents is necessary for reliable NIR-based assessments of tissue-engineered constructs.

Osteogenic Potential of Human Dental Pulp Stem Cells (hDPSCs) Growing on Poly L-Lactide-Co-Caprolactone and Hyaluronic Acid (HYAFF-11TM) Scaffolds

Bone tissue engineering using different scaffolds is a new therapeutic approach in regenerative medicine. This study explored the osteogenic potential of human dental pulp stem cells (hDPSCs) grown on a hydrolytically modified poly(L-lactide-co-caprolactone) (PLCL) electrospun scaffold and a non-woven hyaluronic acid (HYAFF-11™) mesh. The adhesion, immunophenotype, and osteogenic differentiation of hDPSCs seeded on PLCL and HYAFF-11™ scaffolds were analyzed. The results showed that PLCL and HYAFF-11™ scaffolds significantly supported hDPSCs adhesion; however, hDPSCs’ adhesion rate was significantly higher on PLCL than on HYAFF-11™. SEM analysis confirmed good adhesion of hDPSCs on both scaffolds before and after osteogenesis. Alizarin red S staining showed mineral deposits on both scaffolds after hDPSCs osteogenesis. The mRNA levels of runt-related transcription factor 2 (Runx2), collagen type I (Coll-I), osterix (Osx), osteocalcin (Ocn), osteopontin (Opn), bone sialoprotein (Bsp), and dentin sialophosphoprotein (Dspp) gene expression and their proteins were higher in hDPSCs after osteogenic differentiation on both scaffolds compared to undifferentiated hDPSCs on PLCL and HYAFF-11™. These results showed that PLCL scaffolds provide a better environment that supports hDPSCs attachment and osteogenic differentiation than HYAFF-11™. The high mRNA of early osteogenic gene expression and mineral deposits observed after hDPSCs osteogenesis on a PLCL mat indicated its better impact on hDPSCs’ osteogenic potential than that of HYAFF-11™, and hDPSC/PLCL constructs might be considered in the future as an innovative approach to bone defect repair.

Development of a bioactive silk fibroin bilayer scaffold for wound healing and scar inhibition

In cases of deep skin defects, spontaneous tissue regeneration and excessive collagen deposition lead to hyperplastic scars. Conventional remedial action after scar formation is limited with a high recurrence rate. In this study, we designed a new artificial skin bilayer using silk fibroin nanofibers films (SNF) as the epidermis, and silk fibroin (SF) / hyaluronic acid (HA) scaffold as the dermal layer. The regenerated SF film was used as a binder to form a functional SNF-SF-HA bilayer scaffold. The bilayer scaffold showed high porosity, hydrophilicity, and strength, and retained its shape over 30 days in PBS. In vitro, human umbilical vein endothelial cells were seeded into the bilayer scaffold and showed superior cell viability. In vivo analyses using the rabbit ear hypertrophic scar (HS) model indicated that the bilayer scaffold not only supported the reconstruction of new tissue, but also inhibited scar formation. The scaffold possibly achieved scar inhabitation by reducing wound contraction, weakening inflammatory reactions, and regulating collagen deposition and type conversion, which was partly observed through the downregulation of type I collagen, transforming growth factor-β, and α-smooth muscle actin. This study describes a new strategy to expand the application of silk-based biomaterials for the treatment of hyperplastic skin scars.

In-situ wound healing by SDF-1-mimic peptide-loaded click crosslinked hyaluronic acid scaffold

Endogenous stem cell-based in-situ tissue regeneration has recently gained considerable attention. In this study, we investigated the potential of a chemokine, SDF-1-mimic peptide (SMP), to promote endogenous stem cell-based in-situ wound healing. Our approach involved the development of a click crosslinked hyaluronic acid scaffold loaded with SMP (Cx-HA + SMP) to release SMP in a wound site. The Cx-HA scaffold maintained its structural integrity throughout the wound healing process and also captured endogenous stem cells. Gradual SMP release from the Cx-HA + SMP scaffold established a concentration gradient at the wound site. In animal wound experiments, Cx-HA + SMP exhibited faster wound contraction compared to Cx-HA + SDF-1. Additionally, Cx-HA + SMP resulted in approximately 1.2–1.6 times higher collagen formation compared to Cx-HA + SDF-1. SMP released from the Cx-HA + SMP scaffold promoted endogenous stem cell migration to the wound site 1.5 times more effectively than Cx-HA + SDF-1. Moreover, compared to Cx-HA + SDF-1, Cx-HA + SMP exhibited higher expression of CXCR4 and CD31, as well as the positive markers CD29 and CD44 for endogenous stem cells. The endogenous stem cells that migrated through Cx-HA + SMP regenerated into wound skin with minimal scar granule formation, similar to the normal tissue. In conclusion, SMP peptide offers greater convenience, while efficiently attracting migrating endogenous stem cells compared to the SDF protein. Our findings suggest that Cx-HA + SMP scaffolds hold promise as a strategy to enhance endogenous stem cell-based in-situ wound healing.

Rehabilitation of Soccer Players' Knee Injuries: Cartilage Reconstruction, Anterior Cruciate Ligament Surgery, and Intensive Recovery-A Pilot Study.

Knee injuries, particularly anterior cruciate ligament (ACL) damage and cartilage defects, are highly prevalent among athletes and affect their sports performance and long-term joint function. The purpose of this research was to evaluate the effectiveness of a comprehensive combination therapy approach for individuals with ACL and cartilage injuries. Twelve professional soccer players aged 18 to 30 years underwent bone-tendon-bone ACL reconstruction, microfracture cartilage repair surgery, and hyaluronic acid scaffold treatment. Early postoperative rehabilitation included immediate supervised physiotherapy and complete weight bearing. Follow-up assessments involved clinical evaluations, functional joint assessments, and magnetic resonance imaging (MRI) scans to measure cartilage defect repair and symptom alleviation. The results showed that patients resumed pain-free activities within 3-4 weeks and returned to their pre-injury level within 4.5 months. MRI demonstrated the absence of inflammatory reactions, repair of marrow edema, and the emergence of new cartilage. Six months and one year after surgery, the Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Short Form (36) Health Survey (SF-36) questionnaire results demonstrated considerable improvement in patients' health condition and quality of life. Overall, the study suggests that the combination of Hyalofast membranes, microfracture surgery, tissue adhesive, and intensive postoperative physical therapy may be a potential alternative to commonly used treatments for patients with ACL rupture, allowing them to recover efficiently and return to sports activities.

Hyaluronic acid/silicon nanoparticle scaffold induces proliferation and differentiation of mouse spermatogonial stem cells transplanted to epididymal adipose tissue.

Spermatogonia stem cells (SSCs) are a unique cell population maintaining male spermatogenesis during life, through their potential for proliferation and differentiation. The application of silicon nanoparticles (SNs) and hyaluronic acid (HA) to induce the differentiation of SSCs seems promising. Herein, we investigate the effect of SN and HA scaffolds on the progression of SSCs spermatogenesis in mice. Initially SSCs were isolated from healthy immature mice and cultured on prepared scaffolds (HA, SN, and HA/SN) in a 3D culture system. Then viability of SSCs cultured on scaffolds was examined using MTT assay and Acridine Orange staining. Then SSCs cultured on scaffolds were transplanted into epididymal adipose tissue (EAT) in mature mice and the result was studied by H&E and IHC staining 8weeks after transplantation. MTT and Acridine Orange analysis revealed that among three different scaffolds HA/SN based scaffold causes considerable toxicity on SSCs (P < 0.05) while H&E staining showed that culture of SSCs on HA, SN, and HA/SN scaffolds has a positive effect on the progression of SSCs spermatogenesis after transplantation into EAT. IHC staining identified TP1, TEKT1, and PLZF as crucial biomarkers in the spermatogenesis development of SSCs transplanted to EAT. According to the presence of these biomarkers in different experimental groups, we found the most spermatogenesis development in SSCs cultured on HA/SN scaffold (PLZF, P < 0.01) (TEKT1, P < 0.01) (TP1, P < 0.001). Our study showed that, although the cytotoxic effect of the HA/SN scaffold decreases the viability rate of SSCs; however, SSCs that survive on HA/SN scaffold showed more ability to progress in spermatogenesis after transplantation into EAT.

Retrograde "Sandwich" Technique and Implantation of Minced Cartilage in a Hyaluronic Acid Scaffold for Deep Osteochondral Knee Lesions

The management of deep osteochondral lesions is a subject of great controversy. Despite multiple studies and research efforts, it has not been possible to establish an ideal technique for their treatment. The main goal of all available treatments is to avoid the progress toward early osteoarthritis. Hence, this article will present a one-step technique for the handling of osteochondral lesions with a depth equal to or greater than 5 mm, with retrograde subchondral bone grafting to reconstruct the subchondral bone, seeking the greatest possible preservation of the subchondral plate, and implantation of autologous minced cartilage plus a hyaluronic acid–based scaffold (HyaloFast; Anika Therapeutics) under arthroscopic surgery.

Use of 3D-printed Polycaprolactone + Hyaluronic Acid-Based Scaffold in Orthopedic Practice: Report of Two Cases

3D-printed (3DP) polycaprolactone (PCL)-based scaffolds have gained popularity in the past decade. Despite the wide utility of autografts for bone regeneration in orthopedics practice, 3DP PCL scaffolds may replace this general application. Here we present a 42-year-old patient who had glenohumeral arthritis due to rheumatoid arthritis accompanied by a Walch 3 glenoid defect, and a 19-year-old patient with neglected Galeazzi fracture–dislocation accompanied by a radius non-union. In both patients, a 3DP PCL + hyaluronic acid-based scaffold was used for bone regeneration purposes. The preliminary results showed that the 3DP PCL + hyaluronic acid scaffold provided bone regeneration and may be a promising alternative to autografting for bone regeneration in orthopedic practice.

The Manufacture and Characterization of Biomimetic, Biomaterial‐Based Scaffolds for Studying Physicochemical Interactions of Neural Cells in 3D Environments

A particular challenge to the field of neuroscience involves translating findings from 2D in vitro systems to 3D in vivo environments. Standardized cell culture environments that adequately reflect the properties of the central nervous system (CNS) such as the stiffness, protein composition, and microarchitecture in which to study 3D cell-cell and cell-matrix interactions are generally lacking for in vitro culture systems. In particular, there remains an unmet need for reproducible, low-cost, high-throughput, and physiologically relevant environments comprised of tissue-native matrix proteins for the study of CNS microenvironments in 3D. Advances in the field of biofabrication over the past number of years have facilitated the production and characterization of biomaterial-based scaffolds. Typically developed for tissue engineering applications, they also provide sophisticated environments in which to study cell-cell and cell-matrix interactions and have been used for 3D modeling for a range of tissues. Here, we describe a simple and scalable protocol for the production of biomimetic, highly porous freeze-dried hyaluronic acid scaffolds with tunable microarchitecture, stiffness, and protein composition. Furthermore, we describe several different approaches that can be used to characterize a range of physicochemical properties and how to employ the scaffolds for the 3D culture of sensitive CNS cells in vitro. Finally, we detail several approaches for the study of key cell responses within the 3D scaffold environments. Overall, this protocol describes the manufacture and testing of a biomimetic and tunable macroporous scaffold system for neuronal cell culture applications. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Scaffold manufacture Basic Protocol 2: Scaffold characterization Basic Protocol 3: Cell culture and analysis of neurons in scaffolds.

Effect of increasing hyaluronic acid content in collagen scaffolds on the maintenance of chondrogenic phenotype in chondrocytes and mesenchymal stem cells

IntroductionIn articular cartilage, hyaluronic acid (HA) has been shown to increase adhesion, differentiation, and proliferation of cartilage cells, and its addition to three-dimensional (3D) scaffolds has been shown to improve chondrocyte phenotype in vitro. ObjectivesThe purpose of this study was to determine (1) whether increasing the HA levels in collagen scaffolds leads to better maintenance of the chondrogenic phenotype in chondrocytes in a dose-dependent manner and (2) whether collagen scaffolds infused with HA promote the differentiation of mesenchymal stem cells (MSCs) into chondrocytes within 3D collagen/HA scaffolds. MethodsBovine chondrocytes and rat MSCs were seeded onto 2% or 6% collagen/HA scaffolds, or no scaffold for controls. Cells were harvested at days 6, 12 and 18. Real-time polymerase chain reaction was used to measure expression of Type I and Type II collagen, SOX-9, and aggrecan. ResultsExpression of Type I and II collagen was increased at day 18 in the chondrocytes of both groups. For the MSCs, at day 18 there was increased expression of Type I collagen and increased expression of aggrecan in both the 2 and 6% scaffold groups, plus increased SOX-9 expression in the 2% HA group. ConclusionsThough there was no significant dose-dependent change between the HA groups in their effects on Type II collagen production, both HA scaffold groups showed significantly increased expression of Type II collagen as compared to monolayer controls at 18 days. Future experiments should extend timepoints to elucidate these effects and human chondrocytes and MSCs should be used to determine biological applicability.

Satisfactory clinical outcomes with autologous matrix-induced chondrogenesis in the treatment of grade IV chondral injuries of the knee

ObjectiveThe research aims to evaluate short- and medium-term outcomes of patients treated using autologous matrix-induced chondrogenesis (AMIC) with a hyaluronic acid scaffold (Hyalofast, Anika Therapeutics, MA, USA) in grade IV chondral lesions according to the Outerbridge classification in the knee. MethodsThis is a multicentre, non-randomized, retrospective study conducted between 2017 and 2022. To determine the clinical outcome of the patients, the follow-up was done with the subjective International Knee Documentation Committee (IKDC) score, pre-surgery, and with a follow-up at 12, 24, and 32 months. ResultsFifty patients (28 female) with a mean age of 45.9 ± 12.7 years were recruited. The mean size of the lesion was 3.5 cm2, and the injuries located in the patella (30%) and trochlear groove (24%) were the most frequent. The total IKDC clinical score significantly increased from baseline to the 32 months of follow-up with a mean difference of 36.4 (95% CI, 29.1–43.7, p < 0.001). Besides, there was a statistically significant improvement in all categories of the IKDC (symptoms, sports activities, function, and activity of daily living) compared between pre-surgery and 24 and 32 months of follow-up. The patients younger than 45 years presented better clinical outcomes than older ones with a difference between medians of 10.40 (95% CI, 1.10–11.50, p = 0.0247), and a negative correlation was found between the 32-month IKDC score and the age. In addition, no statistically significant difference was found when comparing the last results of the IKDC between patients with and without associated surgical procedures or between patients with single and several lesions, neither nor between men and women. The level of satisfaction with the procedure of all the patients, on a score of 1–10, was on average 8 ± 1.5. ConclusionResults of this study indicate that patients who underwent the AMIC procedure with hyaluronic acid scaffold for the treatment of grade IV chondral lesions in the knee presented satisfactory results throughout the follow-up. Level of evidenceLevel IV

Adipose Autologous Micrograft and Its Derived Mesenchymal Stem Cells in a Bio Cross-Linked Hyaluronic Acid Scaffold for Correction Deep Wrinkles, Facial Depressions, Scars, Face Dermis and Its Regenerations: A Pilot Study and Cases Report.

The aim of this clinical study was to demonstrate that through a micrograft of viable adipose tissue cells microfiltered at 50 microns to exclude fibrous shoots and cell debris in a suspension of cross-linked hyaluronic acid, we were able to improve visible imperfections of the dermis and to improve clinically observable wrinkles, with a beneficial effect also in the extracellular matrix (ECM). Background and Objectives: With the passage of time, the aging process begins, resulting in a progressive impairment of tissue homeostasis. The main reason for the formation of wrinkles is the involution of the papillary dermis, as well as the loss of stem cell niches with compromise of the extra-cytoplasmic matrix (ECM), and the loss of hyaluronic acid, which helps to maintain the shape and resistance and that is contained in the connective tissue. Materials and Methods: This study involved 14 female patients who underwent dermal wrinkle correction and bio-regeneration over the entire facial area through a suspension containing 1.0 mL of viable micrografts from adipose tissue in a 1.0 mL cross-linked hyaluronic acid. To verify the improvement of the anatomical area concerned over time, the various degrees of correction obtained for wrinkles, and in general for texture, were objectively evaluated by using a Numeric Rating scale (NRS) 10-0, a modified Vancouver scale and a Berardesca scale. Results: The Berardesca, NRS and Modified Vancouver scales showed that with this technique it was possible to obtain excellent results both when the suspension was injected into wrinkles with the linear retrograde technique, and when it was injected with the micropomphs technique to correct furrows, with the intent to revitalize the tissue through progenitors with adult stemness markers. Conclusions: The combination of microfragmented and microfiltered adipose tissue and cross-linked hyaluronic acid at 50 microns is safe new method to treat soft tissue defects such as deep wrinkles.

Gelatin/Hyaluronic Acid Scaffold Coupled to CpG and MAGE-A5 as a Treatment against Murine Melanoma.

The half-time of cells and molecules used in immunotherapy is limited. Scaffolds-based immunotherapy against cancer may increase the half-life of the molecules and also support the migration and activation of leukocytes in situ. For this purpose, the use of gelatin (Ge)/hyaluronic acid (HA) scaffolds coupled to CpG and the tumor antigen MAGE-A5 is proposed. Ge and HA are components of the extracellular matrix that stimulate cell adhesion and activation of leucocytes; CpG can promote dendritic cell maturation, and MAGE-A5 a specific antitumor response. C57BL/6 mice were treated with Ge/HA/scaffolds coupled to MAGE-A5 and/or CpG and then challenged with the B16-F10 melanoma cell line. Survival, tumor growth rate and the immune response induced by the scaffolds were analyzed. Ge/HA/CpG and Ge/HA/MAGE-A5 mediated dendritic cell maturation and macrophage activation, increased survival, and decreased the tumor growth rate and a tumor parenchyma with abundant cell death areas and abundant tumor cells with melanin granules. Only the scaffolds coupled to MAGE-A5 induced the activation of CD8 T cells. In conclusion, Ge/HA scaffolds coupled to CpG or MAGE-A5, but not the mixture, can induce a successful immune response capable of promoting tumor cell clearance and increased survival.

Hyaluronic Acid Scaffolds for Loco-Regional Therapy in Nervous System Related Disorders.

Hyaluronic acid (HA) is a Glycosaminoglycan made of disaccharide units containing N-acetyl-D-glucosamine and glucuronic acid. Its molecular mass can reach 10 MDa and its physiological properties depend on its polymeric property, polyelectrolyte feature and viscous nature. HA is a ubiquitous compound found in almost all biological tissues and fluids. So far, HA grades are produced by biotechnology processes, while in the human organism it is a major component of the extracellular matrix (ECM) in brain tissue, synovial fluid, vitreous humor, cartilage and skin. Indeed, HA is capable of forming hydrogels, polymer crosslinked networks that are very hygroscopic. Based on these considerations, we propose an overview of HA-based scaffolds developed for brain cancer treatment, central and peripheral nervous systems, discuss their relevance and identify the most successful developed systems.

Golden Connection Between Stem Cells and Orthopedic Services

Utilization of stem cells in orthopedics has increased dramatically. Consequently, stem cells were discovered to have many roles. Some researchers have used them for regenerative medicine, while some have discovered them as a natural source of immune modulators. Currently, there are several research teams studying the translational potential of stem cells, while clinicians have begun treating patients with orthopedic problems (1).Over the past fifteen years, orthopedic surgeons have prioritized Mesenchymal Stem Cell (MCSs) treatment. Several animal experiments have had favorable results, and there is rising concern over their use in human trials. In these clinical studies, stem cell operations were intended to promote fracture healing and cure nonunion, regenerate articular cartilage in degenerated joints, repair ligament or tendon injuries, and replace degenerative spinal disks (1,2).In past research, stem cells have been used for bone tissue regeneration. Bone tissue engineering presents an alternative treatment that may produce a micromilieu with osteogenic, osteoinductive, and osteoconductive properties. In recent studies, researchers have devised methods for combining MSCs with three-dimensional biodegradable polymeric scaffolds. In addition, Udehiya et al. found that the use of hydroxyapatite scaffolds in conjunction with Bone Marrow-MSCs (BM-MSC) accelerates and enhances the healing of bone segmental defects in a rabbit model compared to the use of hydroxyapatite scaffolds alone. Muwan Chen and colleagues discovered that human BM-MSC combined with hyaluronic acid and b-Tri calcium phosphate-coated polymeric scaffold stimulated osteogenic differentiation, cellular proliferation, and reorganization of the cellular matrix in vitro (1–3).Since 2010, stem cells have undergone a paradigm shift where previously stem cells can differentiate and heal injured organs. This stem cell misunderstanding has led some practitioners in the United States and around the world to advertise the availability of stem cell treatments, e.g., MSC can heal blindness, make paralyzed people walk, and makes old tissue young again. In further studies, it was found that at the site of disease, MSCs rarely or never differentiated into tissue at that location, but they do secrete bioactive factors such as growth factors and their therapeutic effects can be analyzed as a site-specific clinical outcome parameter (2–4).

Application of Injectable, Crosslinked, Fibrin-Containing Hyaluronic Acid Scaffolds for In Vivo Remodeling.

The present research aimed to characterize soft tissue implants that were prepared with the use of crosslinked hyaluronic acid (HA) using two different crosslinkers and multiple reagent concentrations, alone or in combination with fibrin. The effect of the implants was evaluated in an in vivo mouse model, after 4 weeks in one group and after 12 weeks in the other. The explants were compared using analytical methods, evaluating microscopic images, and a histology analysis. The kinetics of the degradation and remodeling of explants were found to be greatly dependent on the concentration and type of crosslinker; generally, divinyl sulfone (DVS) resists degradation more effectively compared to butanediol diglycidyl ether (BDDE). The presence of fibrin enhances the formation of blood vessels, and the infiltration of cells and extracellular matrix. In summary, if the aim is to create a soft tissue implant with easier degradation of the HA content, then the use of 2–5% BDDE is found to be optimal. For a longer degradation time, 5% DVS is the more suitable crosslinker. The use of fibrin was found to support the biological process of remodeling, while keeping the advances of HA in void filling, enabling the parallel degradation and remodeling processes.

Mussel-inspired collagen-hyaluronic acid composite scaffold with excellent antioxidant properties and sustained release of a growth factor for enhancing diabetic wound healing.

Long-term non-healing diabetic wounds are always a serious challenge and a global healthcare burden that needs to be resolved urgently in the clinic. Prolonged inflammation and impaired angiogenesis are the main direct causes of diabetic wounds. With the development of polymer biomaterials, various wound dressings have been created, but a few of them have been applied to the clinical management of diabetic wounds. Here, we developed a mussel-inspired bioactive scaffold consisting mainly of collagen and hyaluronic acid, which are natural biopolymer materials contained in human tissues. First, we fabricated different polydopamine modified lyophilized collagen hyaluronic acid scaffolds under different concentrations of dopamine alkaline solutions, 0.5, 1, 2 ​mg/mL, so named CHS-PDA-0.5, CHS-PDA-1, CHS-PDA-2. After testing their physical and chemical properties, antioxidant effect, inflammation regulation, as well as drug loading and release capabilities, we obtained a bioactive endothelial growth factor (EGF)-loaded wound dressing, CHS-PDA-2@EGF, which can resist reactive oxygen species (ROS) and promote the regeneration of chronic wounds in diabetic rats by reducing inflammation. In addition, the scaffold showed excellent swelling ability, a certain coagulation effect and reasonable degradation. Therefore, the scaffold has great potential to be used in clinical diabetic wound treatment as a low-cost and easily available wound dressing to accelerate chronic wound healing.