Hydrogel Implants Research Articles

Bioink Formulations for Bone Tissue Regeneration.

Unlike the conventional techniques used to construct a tissue scaffolding, three-dimensional (3D) bioprinting technology enables fabrication of a porous structure with complex and diverse geometries, which facilitate evenly distributed cells and orderly release of signal factors. To date, a range of cell-laden materials, such as natural or synthetic polymers, have been deployed by the 3D bioprinting technique to construct the scaffolding systems and regenerate substitutes for the natural extracellular matrix (ECM). Four-dimensional (4D) bioprinting technology has attracted much attention lately because it aims to accommodate the dynamic structural and functional transformations of scaffolds. However, there remain challenges to meet the technical requirements in terms of suitable processability of the bioink formulations, desired mechanical properties of the hydrogel implants, and cell-guided functionality of the biomaterials. Recent bioprinting techniques are reviewed in this article, discussing strategies for hydrogel-based bioinks to mimic native bone tissue-like extracellular matrix environment, including properties of bioink formulations required for bioprinting, structure requirements, and preparation of tough hydrogel scaffolds. Stimulus mechanisms that are commonly used to trigger the dynamic structural and functional transformations of the scaffold are analyzed. At the end, we highlighted the current challenges and possible future avenues of smart hydrogel-based bioink/scaffolds for bone tissue regeneration.

Simultaneous incorporation of PTH(1–34) and nano-hydroxyapatite into Chitosan/Alginate Hydrogels for efficient bone regeneration

Tissue regeneration based on the utilization of artificial soft materials is considered a promising treatment for bone-related diseases. Here, we report cranial bone regeneration promoted by hydrogels that contain parathyroid hormone (PTH) peptide PTH(1–34) and nano-hydroxyapatite (nHAP). A combination of the positively charged natural polymer chitosan (CS) and negatively charged sodium alginate led to the formation of hydrogels with porous structures, as shown by scanning electron microscopy. Rheological characterizations revealed that the mechanical properties of the hydrogels were almost maintained upon the addition of nHAP and PTH(1–34). In vitro experiments showed that the hydrogel containing nHAP and PTH(1–34) exhibited strong biocompatibility and facilitated osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) via the Notch signaling pathway, as shown by the upregulated expression of osteogenic-related proteins. We found that increasing the content of PTH(1–34) in the hydrogels resulted in enhanced osteogenic differentiation of BMSCs. Implantation of the complex hydrogel into a rat cranial defect model led to efficient bone regeneration compared to the rats treated with the hydrogel alone or with nHAP, indicating the simultaneous therapeutic effect of nHAP and PTH during the treatment process. Both the in vitro and in vivo results demonstrated that simultaneously incorporating nHAP and PTH into hydrogels shows promise for bone regeneration, suggesting a new strategy for tissue engineering and regeneration in the future.

Modified hyaluronic acid hydrogels with chemical groups that facilitate adhesion to host tissues enhance cartilage regeneration

Stable integration of hydrogel implants with host tissues is of critical importance to cartilage tissue engineering. Designing and fabricating hydrogels with high adhesive strength, stability and regeneration potential are major challenges to be overcome. This study fabricated injectable adhesive hyaluronic acid (HA) hydrogel modified by aldehyde groups and methacrylate (AHAMA) on the polysaccharide backbone with multiple anchoring mechanisms (amide bond through the dynamic Schiff base reaction, hydrogen bond and physical interpenetration). AHAMA hydrogel exhibited significantly improved durability and stability within a humid environment (at least 7 days), together with higher adhesive strength (43 KPa to skin and 52 KPa to glass), as compared to commercial fibrin glue (nearly 10 KPa) and HAMA hydrogel (nearly 20 KPa). The results showed that AHAMA hydrogel was biocompatible and could be easily and rapidly prepared in situ. In vitro cell culture experiments showed that AHAMA hydrogel could enhance proliferation (1.2-folds after 3 days) and migration (1.5-folds after 12 h) of bone marrow stem cells (BMSCs), as compared to cells cultured in a culture dish. Furthermore, in a rat osteochondral defect model, implanted AHAMA hydrogel significantly promoted integration between neo-cartilage and host tissues, and significantly improved cartilage regeneration (modified O'Driscoll histological scores of 16.0 ± 4.1 and 18.3 ± 4.6 after 4 and 12-weeks of post-implantation in AHAMA groups respectively, 12.0 ± 2.7 and 12.2 ± 2.8 respectively in HAMA groups, 9.8 ± 2.4 and 11.5 ± 2.1 respectively in untreated groups). Hence, AHAMA hydrogel is a promising adhesive biomaterial for clinical cartilage regeneration and other biomedical applications.

Hydrogel-Tissue Adhesion Using Blood Coagulation Induced by Silica Nanoparticle Coatings.

The fixation of hydrogels to biological tissues is a major challenge conditioning the development of implants and surgical techniques. Here, coatings of procoagulant nanoparticles are devised which use the presence of blood to create adhesion between hydrogels and soft internal organs. Those nanostructured coatings are simply adsorbed at the hydrogel surfaces and can rapidly activate the formation of an interfacial blood clot acting as an adhesive joint. This concept is demonstrated on pig liver capsules with model poly(ethylene-glycol) membranes that are intrinsically poorly adhesive. In the absence of blood, ex vivo peeling tests show that coatings with aggregates of bare silica nanoparticles induce a 2- to 4-fold increase in adhesion energy as compared to the uncoated membrane (3 ± 2 J m-2). This effect is found to scale with the specific surface area of the coating. The highest adhesion energies produced by these nanoparticle-coated membranes (10 ± 5 J m-2) approach the value obtained with cyanoacrylate glue (33 ± 11 J m-2) for which tearing of the tissue is observed. Ex vivo pull-off tests show an adhesion strength of coated membranes around 5 ± 1 kPa, which is significantly reduced when operating in vivo (1.0 ± 0.5 kPa). Nevertheless, when blood is introduced at the interface, the in vivo adhesion strength can be improved remarkably with silica coatings, reaching 4 ± 2 kPa after 40 min contact. In addition, these silica-coated membranes can seal and stop the bleeding produced by liver biopsies very rapidly (<30 s). Such a combination of coagulation and particle bridging opens promising routes for better biointegrated hydrogel implants and improved surgical adhesives, hemostats, and sealants.

Efficacy of epicardial implantation of acellular chitosan hydrogels in ischemic and nonischemic heart failure: impact of the acetylation degree of chitosan

This work explores the epicardial implantation of acellular chitosan hydrogels in two murine models of cardiomyopathy, focusing on their potential to restore the functional capacity of the heart. Different chitosan hydrogels were generated using polymers of four degrees of acetylation, ranging from 2.5% to 38%, because the degree of acetylation affects their degradation and biological activity. The hydrogels were adjusted to a 3% final polymer concentration. After complete macromolecular characterization of the chitosans and study of the mechanical properties of the resulting hydrogels, they were sutured onto the surface of the myocardium, first in rat after four-weeks of coronary ligation (n=58) then in mice with cardiomyopathy induced by a cardiac-specific invalidation of serum response factor (n=20). The implantation of the hydrogels was associated with a reversion of cardiac function loss with maximal effects for the acetylation degree of 24%. The extent of fibrosis, the cardiomyocyte length-to-width ratio, as well as the genes involved in fibrosis and stress were repressed after implantation. Our study demonstrated the beneficial effects of chitosan hydrogels, particularly with polymers of high degrees of acetylation, on cardiac remodeling in two cardiomyopathy models. Our findings indicate they have great potential as a reliable therapeutic approach to heart failure.

Peptide Hydrogel Scaffold for Mesenchymal Precursor Cells Implanted to Injured Adult Rat Spinal Cord.

A unique, biomimetic self-assembling peptide (SAP) hydrogel, Fmoc-DIKVAV, has been shown to be a suitable cell and drug delivery system in the injured brain. In this study, we assessed its utility in adult Fischer 344 (F344) rats as a stabilizing scaffold and vehicle for grafted cells after mild thoracic (thoracic level 10 [T10]) contusion spinal cord injury (SCI). Treatments were as follows: Fmoc-DIKVAV alone, Fmoc-DIKVAV containing viable or nonviable rat mesenchymal precursor cells (rMPCs), and rMPCs alone. The majority of post-SCI treatments were administered at 11-15 days (mean 13.5 days) and the results then compared to SCI-only control (no treatment) rats. Postinjury behavior was quantified using open field locomotion (BBB) and LadderWalk analysis. After perfusion at 8 weeks, longitudinal spinal cord sections were immunostained with a panel of antibodies. Qualitatively, in the SAP-only treatment group, implanted gels contained regenerate axons as well as astrocytic, immune cell, and extracellular matrix (ECM) component profiles. Grafts of Fmoc-DIKVAV plus viable or nonviable rMPCs also contained numerous macrophages/microglia and ECM components, but astrocytes were generally confined to implant margins, and axons were rare. Quantitative analysis showed that, while average cyst size was reduced in all experimental groups, the decrease compared to SCI-only controls was only significant in the SAP and rMPC treatment groups. There was gradual improvement in functionality after SCI, but a consistent trend was only seen between the rMPC treatment group and SCI-only controls. In summary, after contusion SCI, implantation of Fmoc-DIKVAV hydrogel provided a favorable microenvironment for cellular infiltration and axonal regrowth, a supportive role that unexpectedly appeared to be compromised by prior inclusion of rMPCs into the gel matrix. Impact statement The self-assembling peptide hydrogel, Fmoc-DIKVAV, is a biomimetic scaffold that is an effective cell and drug delivery system in the injured brain. We examined whether this hydrogel, alone or combined with mesenchymal precursor cells, was also able to stabilise spinal cord tissue after thoracic contusion injury and improve morphological and behavioral outcomes. While improved functionality was not consistently seen, there was reduced cyst size and increased tissue sparing in some groups. There was regenerative axonal growth into hydrogels, but only in initially cell-free implants. This type of polymer is a suitable candidate for further testing in spinal cord injury models.

Evolution of hydrogels for cartilage tissue engineering of the knee: A systematic review and meta-analysis of clinical studies.

In recent years, studies have boosted our knowledge about the biology and disorders of articular cartilage. In this regard, the design of hydrogel-based scaffolds has advanced to improve cartilage repair. However, the efficacy of knee cartilage repair using hydrogels remains unclear. The aim of systematic review and meta-analysis was to scrutinize the efficiency of hydrogel-based therapy in correcting cartilage defects of knee (femoral condyle, patella, tibia plateau and trochlea). The search was conducted in PubMed to gather articles published from 2004/1/1 to 2019/10/01, addressing the effects of implant of hydrogel on knee joint cartilage regeneration. The Cochrane Collaboration's tool for estimating the risk of bias was applied to check the quality of articles. The clinical data for meta-analysis was recorded using the visual analog scale (VAS), Lysholm score, WOMAC, and IKDC. The guidelines of Cochrane Handbook for Systematic Reviews of Interventions were utilized to conduct the review and meta-analysis in the RevMan 5.3 software. The search resulted in 50 clinical trials that included 2846 patients, 986 of whom received cell-based hydrogel implants while 1860 patients used hydrogel without cell. There were significant differences comparing the pain scores based on the VAS (MD: -2.97; 95% CI: -3.15 to -2.79, P<0.00001) and WOMAC (MD: -25.22; 95% CI: -31.22 to -19.22, P<0.00001) between pre- and post-treatment with hydrogels. Furthermore, there were significant improvements in the functional scores based on the IKDC total score (MD: 30.67; P<0.00001) and the Lysholm knee scale (MD: 29.26; 95% CI: 26.74 to 31.78, P<0.00001). According to the Lysholm and IKDC score and after cumulative functional analysis, there was a significant improvement in this parameter (MD: 29.25; 95% CI: 27.26 to 31.25, P<0.00001). This meta-analysis indicated clinically and statistically significant improvements in the pain score (VAS and WOMAC) and the functional score (IKDC and Lysholm) after the administration of hydrogel compared to pretreatment status. So, the current evidence shows the efficiency of hydrogel-based therapy in correcting and repairing knee cartilage defects.

A porous collagen-based hydrogel and implantation method for corneal stromal regeneration and sustained local drug delivery

Biomaterials designed to replace the diseased cornea could be used to treat corneal blindness where human donor tissue is in short supply, but challenges are the integration of biomaterials with host tissue and cells, avoiding a rapid material degradation and maintaining corneal transparency. Additionally, implantation surgery often triggers an aggressive wound healing response that can lead to corneal thinning and opacity. Here, we report a collagen-based hydrogel with transparency and mechanical properties suitable for replacing a substantial portion of a damaged or diseased corneal stroma. The porous hydrogel permitted migration and population by host cells while maintaining transparency and thickness six months after surgical implantation in an in vivo model of human corneal surgery. With a novel hybrid surgical implantation technique inspired by LASIK refractive surgery, rapid wound healing occurred around implants to maintain biomaterial integrity, transparency and function. Host stromal cell repopulation and regeneration of host epithelium and nerves were observed, as necessary steps towards corneal regeneration. Finally, as a proof-of-principle, the hydrogel loaded with a neuroregenerative drug achieved sustained slow-release drug delivery in vitro. The proposed hydrogel and novel implantation technique together represent a therapeutic approach with translational potential for replacing and regenerating diseased corneal stromal tissue.

Patient Outcomes Following Polyvinyl Alcohol Hydrogel Implant of the Lesser Metatarsals

Category:Lesser Toes; OtherIntroduction/Purpose:Lesser toe metatarsal phalangeal (MTP) joint pathology presents a challenge for surgical treatment. Recently, synthetic cartilage implants have been shown to be safe and efficacious in treating hallux ridigus, offering pain relief while preserving motion at the MTP joint. At our institution, metatarsophalangeal joint arthroplasty using a polyvinyl alcohol (PVA) hydrogel implant has been utilized in the 2nd and 3rd MTP joints for advanced arthritis, failed management of Freiberg’s infraction, and osteochondral defects. We present a case series describing the clinical outcomes of 12 patients following PVA implantation of the 2nd or 3rd MTP.Methods:We retrospectively identified 12 consecutive patients (13 joints) who underwent PVA hydrogel implantation of the 2nd (n=12) or 3rd (n=1) metatarsal head between 2017 and 2019. PVA implant was indicated for advanced arthritis in 6 patients (7 joints), Freiberg’s infraction in 4 patients, and osteochondral defect in 2 patients. Average age was 51 years (range, 20-67), with 100% females. Patient-reported outcomes measurement information system (PROMIS) scores were collected preoperatively and at latest follow-up, with an average follow-up of 20.4 months (range, 8.3 to 29.2). Retrospective chart review was performed to evaluate postoperative complications, including need for revision, implant removal, and persistent pain.Results:Overall, patients demonstrated mean improvement in all PROMIS domains, with a significant improvement in Pain Intensity of 11.9 points (p=0.03) postoperatively. A total of 4 postoperative complications occurred in the 12 patients: one case of AVN at 2 years postoperatively, one revision with removal of the implant and bone grafting of the second metatarsal head at 1 year postoperatively, one periprosthetic fracture at 9 months postoperatively, and one recurrence of pain requiring ultrasound- guided injection at 7 months postoperatively. Three additional patients reported persistent pain postoperatively.Conclusion:This study represents the largest case series to date evaluating the use of PVA hydrogel implant in the surgical correction of lesser toe MTP joint pathology. While the PVA implant presents a viable option in the setting of advanced arthritis, Freiberg’s infraction, and certain osteochondral defects, it is not without complications. The specific indications for use of the PVA implant should be carefully considered before implantation.

Early Outcomes of a Synthetic Cartilage Implant for Treatment of Hallux Rigidus: A Series of 87 Patients

Category:Midfoot/Forefoot; BunionIntroduction/Purpose:Arthritis of the first metatarsophalangeal joint (MTPJ), or hallux rigidus, is the most common arthritic condition of the foot, affecting 1 in 40 people over 50 years of age. One surgical option is the implantation of a synthetic polyvinyl alcohol hydrogel implant that has water content, tensile strength, and biomechanical properties similar to those of healthy human cartilage. This implant is supported by positive outcomes in a Level 1 clinical trial out to over 5 years follow-up. The objective of this case series was to determine if the positive results seen in the pivotal trial could be recreated in a ‘real world’ setting.Methods:All patients implanted with a synthetic cartilage implant by a single surgeon between September 2016 and December 2018 were retrospectively reviewed. Consecutive adult patients diagnosed with hallux rigidus that failed nonoperative treatment were included in the analysis. Patient demographics, complications, Foot and Ankle Ability Measures (FAAM), and a 10-point visual analog score (VAS) were collected from the chart review.Results:A total of 87 patients were available for review during the time interval of interest with a mean length of follow-up of 38.7 weeks (range, 2-125). The average patient age was 56.6 years (range, 21-80). Two (2.3%) patients were converted to fusion. The first at 71 weeks and the second at 73 weeks following the initial surgery. Six (6.9%) patients experienced some complications: 3 cases of synovitis treated with corticosteroid injection; 1 case of sesamoiditis; 1 case of neuritis; and 1 insufficiency fracture at the plantar aspect of the MTPJ with implant subsidence. Patients had mean FAAM ADL and VAS scores of 81.2 (range 21-100) and 0.6 (range, 0-3), respectively, at final follow-up.Conclusion:This retrospective review is one of the first presentations of outcomes for a synthetic cartilage implant in a ‘real world’ setting. Patients experienced excellent pain relief, good functional outcomes, and a satisfactory survival rate. This case series confirms the positive results seen in the original pivotal trial for this device.

Scaffold-Mediated Gene Delivery for Osteochondral Repair.

Osteochondral defects involve both the articular cartilage and the underlying subchondral bone. If left untreated, they may lead to osteoarthritis. Advanced biomaterial-guided delivery of gene vectors has recently emerged as an attractive therapeutic concept for osteochondral repair. The goal of this review is to provide an overview of the variety of biomaterials employed as nonviral or viral gene carriers for osteochondral repair approaches both in vitro and in vivo, including hydrogels, solid scaffolds, and hybrid materials. The data show that a site-specific delivery of therapeutic gene vectors in the context of acellular or cellular strategies allows for a spatial and temporal control of osteochondral neotissue composition in vitro. In vivo, implantation of acellular hydrogels loaded with nonviral or viral vectors has been reported to significantly improve osteochondral repair in translational defect models. These advances support the concept of scaffold-mediated gene delivery for osteochondral repair.

Enzyme-mediated one-pot synthesis of hydrogel with the polyphenol cross-linker for skin regeneration.

Polyphenols can trigger immunity that activates intracellular anti-inflammatory signaling and prevents external infections. In this study, we report the fabrication of chitosan-based hydrogels with epigallocatechin gallate (EGCG) using enzyme-mediated one-pot synthesis. The tyrosinase-mediated oxidative reaction of the phenolic rings of EGCG with the primary amines on chitosan results in stable EGCG-chitosan hydrogels. The EGCG concentrations contributed to the cross-linking density and physical properties of EGCG-chitosan hydrogels. Furthermore, EGCG-chitosan hydrogels maintained intrinsic properties such as antibacterial and antioxidant effects. When endotoxin-activated RAW 264.7 macrophage cells were cultured with EGCG-chitosan hydrogels, the hydrogels reduced the inflammatory response of the RAW 264.7 cells. Furthermore, subcutaneous implantation of EGCG-chitosan hydrogels reduced endogenous macrophage and monocyte activation. When the EGCG-chitosan hydrogels were applied to a full-skin defect wound, they facilitated skin regeneration. Our study demonstrates that the one-pot synthesized EGCG-chitosan hydrogels can be applied in broad tissue regeneration applications that require immune modulation.

Enzyme-Cross-linked Gelatin Hydrogel Enriched with an Articular Cartilage Extracellular Matrix and Human Adipose-Derived Stem Cells for Hyaline Cartilage Regeneration of Rabbits.

Hyaline cartilage regeneration remains clinically challenging. In this study, microbial transglutaminase was used to cross-link gelatin. The articular cartilage extracellular matrix (cECM), mainly comprising collagen type II and glycosaminoglycans (GAGs), which can support chondrogenesis, was enclosed in this enzyme-catalyzed hydrogel. After human adipose-derived stem cells (hASCs) were encapsulated in the hydrogel enriched with the cECM, the results demonstrated that the enzymatic cross-linking reaction is of low cytotoxicity. Moreover, the stem cells showed great proliferation and chondrogenic differentiation potential in the hydrogel. Most importantly, we assessed the therapeutic effects of applying a hydrogel enriched with the cECM and hASCs to repair a full-thickness osteochondral defect. At 8 weeks after surgery, the GCC group (hydrogel encapsulating cells and the cECM) exhibited a smooth articular surface with transparent new hyaline-like tissue macroscopically. According to histological analysis, inflammatory responses were hardly observed, and sound chondrocytes were aligned in the newly formed chondral layer. In addition, the GCC group exhibited significant improvement in the GAG content between weeks 4 and 8. In summary, the implantation of a gelatin hydrogel enriched with the cECM and hASCs could facilitate the hyaline cartilage regeneration significantly in rabbit knee joint models.

The Prevalence of Self-Reported Health Complaints and Health-Related Quality of Life in Women With Breast Implants

BackgroundSome of the millions of women with silicone breast implants (SBIs) report a pattern of systemic complaints, known as ASIA syndrome. However, the association between these complaints and breast implants remains uncertain.ObjectivesThis study aimed to evaluate the prevalence of complaints in women with breast implants and healthy controls, and to compare their health-related quality of life.MethodsFour groups of subjects were requested to fill in a general and a diagnostic questionnaire, and the Short Form 36. Group 1 was recruited from the Dutch foundation for breast implant illness (BII). Two groups were recruited from Dutch hospitals, where they had been augmented or reconstructed with SBIs (group 2) or saline-filled and hydrogel implants (group 3). A control group without breast implants was recruited from friends of subjects from group 2.ResultsIn total, 238 women completed the questionnaires. ASIA manifestations appeared in the majority of the respondents (72.3%-98.8%), with a latency period of 0 to 35 years. Adjusted for age, smoking, and comorbidities, typical symptoms only occurred significantly more frequently in group 1. The presence of a chronic disease was an independent predictor for ASIA syndrome. The health-related quality of life was lower in women with SBIs than in women without breast implants.ConclusionsThe adjusted prevalence of BII manifestations is not significantly higher in women with SBIs than in women without implants. The findings of this study suggest that results on BII are subject to selection bias. Further studies are needed to prove an association between self-reported complaints and SBIs.Level of Evidence: 2

Outcomes of Polyvinyl Alcohol Hydrogel Implant of the Lesser Metatarsals.

Lesser toe metatarsophalangeal (MTP) joint pathology presents a challenge for surgical treatment. At our institution, arthroplasty using a polyvinyl alcohol (PVA) hydrogel implant has been utilized in the second and third MTP joints for advanced arthritis, failed management of Freiberg's infraction, and osteochondral defects. We present a case series describing the clinical outcomes of 13 patients following PVA implantation of the second or third MTP. We retrospectively identified 13 patients (14 joints) who underwent PVA hydrogel implantation of the second (n = 12) or third (n = 2) metatarsal between 2017 and 2019. The average age was 49 (range, 20-67) years, with 100% females. Patient-Reported Outcomes Measurement Information System (PROMIS) scores were collected preoperatively and at an average of 21.1 (range, 8.3-29.2) months postoperatively. Clinical outcomes were also evaluated. The average time to clinical follow-up was 24.7 (range, 7-35.8) months. On average, patients demonstrated pre- to postoperative improvement in all PROMIS domains, with significant improvements in Pain Intensity (P = .01) and Pain Interference (P = .01). Five postoperative complications were observed: 1 case of persistent avascular necrosis, 1 revision with implant removal and bone grafting, 1 periprosthetic fracture, and 2 recurrences of pain requiring ultrasound-guided injection. This study represents the largest case series to date evaluating the use of PVA implant in the surgical correction of lesser toe MTP joint pathology. While the PVA implant presents a viable option in the setting of advanced arthritis, Freiberg's infraction, and certain osteochondral defects, it is not without complications. The specific indications for use of the PVA implant should be carefully considered. Level IV, case series.

In vitro Evaluation of ASCs and HUVECs Co-cultures in 3D Biodegradable Hydrogels on Neurite Outgrowth and Vascular Organization.

Vascular disruption following spinal cord injury (SCI) decisively contributes to the poor functional recovery prognosis facing patients with the condition. Using a previously developed gellan gum hydrogel to which the adhesion motif GRGDS was grafted (GG-GRGDS), this work aimed to understand the ability of adipose-derived stem cells (ASCs) to impact vascular organization of human umbilical vein endothelial cells (HUVECs), and how this in turn affects neurite outgrowth of dorsal root ganglia (DRG) explants. Our data shows that culturing these cells together lead to a synergistic effect as showed by increased stimulation of neuritogenesis on DRG. Importantly, HUVECs were only able to assemble into vascular-like structures when cultured in the presence of ASCs, which shows the capacity of these cells in reorganizing the vascular milieu. Analysis of selected neuroregulatory molecules showed that the co-culture upregulated the secretion of several neurotrophic factors. On the other hand, ASCs, and ASCs + HUVECs presented a similar profile regarding the presence of angiotrophic molecules herein analyzed. Finally, the implantation of GG-GRGDS hydrogels encapsulating ASCs in the chick chorioallantoic membrane (CAM) lead to increases in vascular recruitment toward the hydrogels in comparison to GG-GRGDS alone. This indicates that the combination of ASCs with GG-GRGDS hydrogels could promote re-vascularization in trauma-related injuries in the central nervous system and thus control disease progression and induce functional recovery.

Regenerative histogenesis in a skeletal muscle defect with local implantation of gene-activated hydrogel based on hyaluronic acid in the experiment

Optimization of the reparative regeneration of striated skeletal muscle tissue is actual for clinical practice. Volumetric muscle loss usually heals through the fibrous scar formation. Herein, there are numerous of methods under developed focused on reparative myogenesis induction. One of the promising approaches in this area is formed by gene-activated materials, particularly, in the hydrogel form. We developed a gene-activated hydrogel based on hyaluronic acid and plasmid DNA with the gene of vascular endothelial growth factor A (VEGF-A). Firstly, we showed a biocompatibility of the product in the subcutaneous test in mice. Using marker plasmid DNA carrying the luciferase gene, prolonged delivery of gene constructs to cells in vivo with a peak in transgene expression at day 7 was confirmed, while the same plasmid DNA in an aqueous solution provided a maximum level of delivery at day 1. Being implanted into a volumetric defect of the anterior tibial muscle in rats the gene-activated hydrogel activated angiogenesis in 2 weeks after surgery and induced MYH7B+-muscle fibers formation in the central zone of the defect at average number 50,0±16,1 and 21,8±10,5 in 2 and 4 weeks, respectively, whereas a hydrogel without plasmid DNA did not have any myogenic effects. Thus, plasmid DNA with VEGFA in the sodium alginate-based hydrogel induced angiogenesis in the volumetric muscle loss model and stimulated reparative myogenesis that could be used for further development of products effective for treatment of patients with muscle pathology.

Динаміка депонування та дифузії лікарських препаратів (хлоргексидин, 5 фторурацил і доксорубіцин) при використанні гідрогелевих імплантатів з різною щільністю

Динаміка депонування та дифузії лікарських препаратів (хлоргексидин, 5 фторурацил і доксорубіцин) при використанні гідрогелевих імплантатів з різною щільністю

Local Serpin Treatment via Chitosan-Collagen Hydrogel after Spinal Cord Injury Reduces Tissue Damage and Improves Neurologic Function.

Spinal cord injury (SCI) results in massive secondary damage characterized by a prolonged inflammation with phagocytic macrophage invasion and tissue destruction. In prior work, sustained subdural infusion of anti-inflammatory compounds reduced neurological deficits and reduced pro-inflammatory cell invasion at the site of injury leading to improved outcomes. We hypothesized that implantation of a hydrogel loaded with an immune modulating biologic drug, Serp-1, for sustained delivery after crush-induced SCI would have an effective anti-inflammatory and neuroprotective effect. Rats with dorsal column SCI crush injury, implanted with physical chitosan-collagen hydrogels (CCH) had severe granulomatous infiltration at the site of the dorsal column injury, which accumulated excess edema at 28 days post-surgery. More pronounced neuroprotective changes were observed with high dose (100 µg/50 µL) Serp-1 CCH implanted rats, but not with low dose (10 µg/50 µL) Serp-1 CCH. Rats treated with Serp-1 CCH implants also had improved motor function up to 20 days with recovery of neurological deficits attributed to inhibition of inflammation-associated tissue damage. In contrast, prolonged low dose Serp-1 infusion with chitosan did not improve recovery. Intralesional implantation of hydrogel for sustained delivery of the Serp-1 immune modulating biologic offers a neuroprotective treatment of acute SCI.

Proposed Hydrogel-Implant Quality Score and a Matched-Pair Study for Prostate Radiation Therapy

PurposeSpaceOAR hydrogel has been Food and Drug Administration approved to reduce rectal toxicity in prostate radiation therapy. Training and certification for this procedure is performed by the manufacturer, without independent quality measures. We propose a Hydrogel-Implant Quality Score (HIQS) as a surrogate to quantify hydrogel placement accuracy, to assist clinicians in tracking their implant proficiency, and to support quality improvement. A matched-pair study was designed to investigate the benefit of SpaceOAR in rectal dose reduction for low-dose-rate brachytherapy and to validate the principle of the proposed HIQS. MethodsEighty-one prostate patients were retrospectively selected for this study. Each patient had SpaceOAR implantation under manufacturer supervision. Postprocedure computed tomography and T2-weighted magnetic resonance imaging were acquired for radiation planning. A HIQS system was proposed to evaluate the hydrogel placement quality. Hydrogel implantation was performed immediately after LDR seed placement. For each LDR patient, a non-SpaceOAR patient was matched based upon intraoperative rectal dose and prostate coverage. Intraoperative and postoperative rectal dose reduction was compared between SpaceOAR and non-SpaceOAR groups. ResultsThe average HIQS was 77 ± 10.8 (range, 49-97). Rectal anatomic distortions were seen in 17 cases. Significant rectal dose reductions between intraoperative and postoperative plans were found for SpaceOAR patients compared with non-SpaceOAR patients (25.1 Gy vs −5.0 Gy for ΔD2cc and 65.7 Gy vs 13.0 for ΔD0.1cc). Additional rectal dose reductions (8.4 Gy for ΔD2cc and 12.7 Gy for ΔD0.1cc) were found for patients without rectal distortion when SpaceOAR was used. ConclusionsThe proposed HIQS system measured the hydrogel placement quality and provided insights into clinician learning and DVH outcome. SpaceOAR was shown to be effective in reducing rectal dose for LDR patients.