Nanoparticles for the treatment of spinal cord injury

Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a slow process, partly due to the difficulty of delivering drugs effectively. Nanoparticles, with their targeted delivery capabilities, biocompatibility, and enhanced bioavailability over conventional drugs, are garnering attention for spinal cord injury treatment. This review explores the current mechanisms and shortcomings of existing treatments, highlighting the benefits and progress of nanoparticle-based approaches. We detail nanoparticle delivery methods for spinal cord injury, including local and intravenous injections, oral delivery, and biomaterial-assisted implantation, alongside strategies such as drug loading and surface modification. The discussion extends to how nanoparticles aid in reducing oxidative stress, dampening inflammation, fostering neural regeneration, and promoting angiogenesis. We summarize the use of various types of nanoparticles for treating spinal cord injuries, including metallic, polymeric, protein-based, inorganic non-metallic, and lipid nanoparticles. We also discuss the challenges faced, such as biosafety, effectiveness in humans, precise dosage control, standardization of production and characterization, immune responses, and targeted delivery in vivo. Additionally, we explore future directions, such as improving biosafety, standardizing manufacturing and characterization processes, and advancing human trials. Nanoparticles have shown considerable progress in targeted delivery and enhancing treatment efficacy for spinal cord injuries, presenting significant potential for clinical use and drug development.

Bone Remodeling, Biomaterials And Technological Applications: Revisiting Basic Concepts

Presently, several different graft materials are employed in regenerative or corrective bone surgery. However current misconceptions about these biomaterials, their use and risks may compromise their correct application and development. To unveil these misconceptions, this work briefly reviewed concepts about bone remodeling, grafts classification and manufacturing processes, with a special focus on calcium phosphate materials as an example of a current employed biomaterial. Thus a search on the last decade was performed in Medline, LILACS, Scielo and other scientific electronic libraries using as keywords biomaterials, bone remodeling, regeneration, biocompatible materials, hydroxyapatite and therapeutic risks. Our search showed not only an accelerated biotechnological development that brought significant advances to biomaterials use on bone remodeling treatments but also several therapeutic risks that should not be ignored. The biomaterials specificity and limitations to clinical application point to the current need for developing safer products with better interactions with the biological microenvironments.

Update on the use of 45S5 bioactive glass in the treatment of bone defects in regenerative medicine

Bone regeneration is a critical area in regenerative medicine,particularly in orthopedics,demanding effective biomedical materials for treating bone defects.45S5 bioactive glass(45S5 BG)is a promising material because of its osteoconductive and bioactive properties.As research in this field continues to advance,keeping up-to-date on the latest and most successful applications of this material is imperative.To achieve this,we conducted a comprehensive search on Pub-Med/MEDLINE,focusing on English articles published in the last decade.Our search used the keywords“bioglass 45S5 AND bone defect”in combination.We found 27 articles,and after applying the inclusion criteria,we selected 15 studies for detailed examination.Most of these studies compared 45S5 BG with other cement or scaffold materials.These comparisons demonstrate that the addition of various composites enhances cellular biocompatibility,as evidenced by the cells and their osteogenic potential.Moreover,the use of 45S5 BG is enhanced by its antimicrobial properties,opening avenues for additional investigations and applications of this biomaterial.

Effects of Taxotere on invasive potential and multidrug resistance phenotype in pancreatic carcinoma cell line SUIT-2

INTRODUCTIONDevelopment of drug-resistance to chemotherapyand subsequent metastasis of tumor are primarilyresponsible for treatment failure and the death fromcancer. There have been many previous studies onthe relationship between expression of multidrugresistance (MDR) phenotype P-glycoprotein (P-gp)and the malignant properties of tumors, but theresults are often conflicting[1-8]. The difference intumor types or MDR phenotype induced by specificagents might account for this discrepancy. Taxotere(TXT), a member of the family of taxanes, hasantitumor activity through its effect of promotingthe polymerization of tubulin[9,10].

Biocompatibility of KLD-12 Peptide Hydrogel as a Scaffold in Tissue Engineering of Intervertebral Discs in Rabbits

KLD-12 peptide with a sequence of AcN-KLDLKLDLKLDL-CNH2 was synthesized and its biocompatibility was assessed in animals. Rabbit MSCs were cultured in the hydrogel for 2 weeks. Live cells were counted by using Calcein-AM/P1 fluorescence staining. MTT was employed to assess the viability of MSCs cultured in KLD-12 peptide solution of 0.01%, 0.03%, and 0.05%. Hemolysis test, skin irritation test and implantation test were conducted to evaluate its biocompatibility with host tissues. Our results demonstrated that the MSCs in hydrogel grew well and maintained round shape. Cell survival rate was 92.15% （mean： 92.15%±1.17%） at the 7th day and there was no difference in survival rate between day 7 and day 14. Cell proliferation test showed that the A value of the KLD-12 solutions was not significantly different from that of control groups （complete culture media） （P〉0.05） at the 24th and 48th h. The hemolysis rate of KLD-12 solution was 0.112%. Skin irritation test showed that the skin injected with KLD-12 solution remained normal and the score of skin irritation was 0. The histological examination with HE staining exhibited that the skin layers were clear and there was no infiltration with neutrophilic granulocytes and lymphocytes. It is concluded that KLD-12 peptide hydrogel bad a good biocompatibility with host rabbit and MSCs, and KLD-12 pep- tide hydrogel can provide an appropriate microenvironment for MSCs.

Surface Characterization and Tribology Behavior of PMMA Processed by Excimer Laser

Polyoxymethylene methacrylate (PMMA) is widely used in ophthalmic biomaterials. Misuse of PMMA in extreme environments is likely to damage the ocular surface and intraocular structures. The surface characterization and tribological behavior of PMMA processed using an excimer laser were investigated in this study by contrasting diferent lubrication conditions and friction cycles. The results show that the roughness of the material surface increases with laser processing, which changes its physical structure. Under lubrication, the laser-treated PMMA exhibits better hydrophilicity, especially during the use of eye drops. No obvious relationship exists between the laser-processing time and friction behavior. However, the laser treatment may contribute to the formation of friction and wear mechanisms of PMMA materials. Laser-treated PMMA in saline solution exhibits better abrasive resistance by showing a lower wear rate than that in eye drops, although it has a higher friction coefcient. In this study, the diferent friction stages in laser-treated PMMA were clarifed under two lubrication conditions. The wear rates of the laser-treated PMMA were found to decrease with the number of cycles, and the friction coefcient has a similar variation tendency. The wear behavior of the laser-treated PMMA is dominated by the main abrasive wear and secondary transferred flm formation. This study provides a theoretical basis for the development and application of ophthalmic biomaterials in complex environments by examining the material surface interface behavior and wear mechanism after laser processing using PMMA as the research matrix.

IMMOBILIZATION OF POTENTIALLY BIOACTIVE MOIETIES ONTO POLYETHER WITH POLY(ETHYLENE GLYCOL)-SULFONATE SPACER

A new reactive graft copolymer, poly(tetramethylene glycol)-graft-omega-propyl sodium sulfonate-poly(ethylene glycol) (PTMG-g-PEG-CH2CH2CH2SO3-Na+), was synthesized by the cationic polymerization of alpha-omega-bifunctional PEG macromonomer ((sic)CH2-PEG-CH2CH2CH2SO3Na) and THF. The obtained copolymer exhibits the expected structure as indicated by the result of characterization. Two amino acids (L-arginine, L-tyrosine) were covalently attached to the copolymer after converting the sulfonate group, to sulfonyl chloride. So the new reactive graft copolymer (PTMG-g-PEG-CH2CH2CH2SO3-Na+) is expected to be very useful in attachment of potentially bioactive moieties to polymer via a hydrophilic PEG spacer.

Comparative Dimensional and Microscopic Analysis of the Strength and Hardness of Internal Fixation Plates

The fixation stability achieved with the use of plates and screws in oral and maxillofacial surgery is a decisive factor in treatment success. The mechanical and structural properties of the internal fixation materials have direct influence on the dimensional stability and resistance of a fixation system, thus influencing treatment outcomes. This study proposed to analyze the dimensional and resistance patterns of titanium plates used for obtaining stable fixation in orthognathic surgery and craniofacial trauma. For this study, 30 conventional 2.0 mm straight four hole plates with bridge from three brands commercialized in Brazil, were subjected to macroscopic, microscopic, strength and hardness analysis. The dimensional measurements were performed using a digital caliper. Energy-dispersive X-ray spectroscopy analysis was performed by scanning electron microscopy to analyze the chemical composition of the samples. The mechanical resistance tests were performed with a universal testing machine. The samples were then submitted to Vickers hardness analysis, complying with the standards of ASTM E92. The data collected from the dimensional study was submitted to statistical analysis of the coefficient of variation, while the values obtained during the mechanical tests were analyzed by variance (ANOVA) and Tukey’s test (p < 0.05). The sample groups presented different performances in resistance, hardness, size and surface, even though they were reported to be chemically similar compounds that allowed us to conclude the plates from Group 2 were more resistant than groups 1 and 3.

Tissue engineering approaches for dental pulp regeneration:The development of novel bioactive materials using pharmacological epigenetic inhibitors

The drive for minimally invasive endodontic treatment strategies has shifted focus from technically complex and destructive root canal treatments towards more conservative vital pulp treatment.However,novel approaches to maintaining dental pulp vitality after disease or trauma will require the development of innovative,biologicallydriven regenerative medicine strategies.For example,cell-homing and cell-based therapies have recently been developed in vitro and trialled in preclinical models to study dental pulp regeneration.These approaches utilise natural and synthetic scaffolds that can deliver a range of bioactive pharmacological epigenetic modulators(HDACis,DNMTis,and ncRNAs),which are cost-effective and easily applied to stimulate pulp tissue regrowth.Unfortunately,many biological factors hinder the clinical development of regenerative therapies,including a lack of blood supply and poor infection control in the necrotic root canal system.Additional challenges include a need for clinically relevant models and manufacturing challenges such as scalability,cost concerns,and regulatory issues.This review will describe the current state of bioactive-biomaterial/scaffold-based engineering strategies to stimulate dentine-pulp regeneration,explicitly focusing on epigenetic modulators and therapeutic pharmacological inhibition.It will highlight the components of dental pulp regenerative approaches,describe their current limitations,and offer suggestions for the effective translation of novel epigenetic-laden bioactive materials for innovative therapeutics.

Rationalizing the Development of Biomaterials with A New Way of Thinking

The history of biomaterials research is seriously surveyed. It is found that an immutable way of thinking for developing biomaterials is rooted deeply in Western medicine and biology. It is necessary to modify or change the current status of thinking. In this paper, the author presents an idea to research and develop biomaterials via a combined way of thinking, i.e., combining together the wisdom and knowledge of Western medicine, Chinese medicine, and other disciplines.

Novel three-dimensional nerve tissue engineering scaffolds and its biocompatibility with Schwann cells

Objective： To develop a novel scaffolding method for the copolymers poly lactide-co-glycolide acid （PLGA） to construct a three-dimensional （3-D） scaffold and explore its biocompatibility through culturing Schwann cells （SCs） on it. Methods： The 3-D scaffolds were made by means of melt spinning, extension and weaving. The queueing discipline of the micro-channels were observed under a scanning electronic microscope （SEM）.The sizes of the micropores and the factors of porosity were also measured. Sciatic nerves were harvested from 3-day-old Sprague Dawley （SD） rats for culture of SCs. SCs were separated, purified, and then implanted on PLGA scaffolds, gelatin sponge and poly-L-lysine （PLL）-coated tissue culture poly-styrene （TCPS） were used as biomaterial and cell-supportive controls, respectively. The effect of PLGA on the adherence, proliferation and apoptosis of SCs were examined in vitro in comparison with gelatin sponge and TCPS. Results： The micro-channels arrayed in parallel manners, and the pore sizes of the channels were uniform. No significant difference was found in the activity of Schwann cells cultured on PLGA and those on TCPS （P〉0.05）, and the DNA of PLGA scaffolds was not damaged. Conclusion： The 3-D scaffolds developed in this study have excellent structure and biocompatibility, which may be taken as a novel scaffold candidate for nerve-tissue engineering.

Progress in various crosslinking modification for acellular matrix

Objective To review the current crosslinking strategies for acelluar matrix scaffold,laying the foundation for subsequent experiment.Data sources Data were mainly obtained from recent papers published in PubMed or indexed by Web of Science,with keyword like crosslinking.Results Various crosslinking strategies,including chemical,physical and biological methods,have been introduced to facilitate the performance of fresh acellular matrix.Chemical crosslinking reagents,involved in synthetic and naturally derived agents,need to be eliminated before implantation in case of their potential biotoxicity,although several crosslinking agents with less toxicity and specific characteristics have been developed.Physical crosslinking methods present to be safe,additive-free and relatively controllable for rapid surface functionalization with no consideration of remaining radioactivity.Biological crosslinking strategies have attracted great interest,and have been demonstrated to enhance collagen-based crosslinking since their preparations do not need toxic or potentially biologically contaminated substances and can be carried out under physiological conditions.Conclusions Kinds of crosslinking methods with its potential advantages have been developed to modify raw acelluar matrix,of which the performance are promising after being crosslinked by several crosslinking treatments.Further preclinical and clinical evaluations should be taken to vertify their safety and efficacy for the tissues and organs substitutes in tissue and regenerative medicine.

听骨赝复物

随着耳显微外科的迅速发展，鼓室成形术逐渐推广，对听骨链重建材料的研究也逐步深入，现就国内外对听骨链重建材料的研究现状进行综述。

Biocompatibility and degradation comparisons of four biodegradable copolymeric osteosynthesis systems used in maxillofacial surgery: A goat model with four years follow-up

pplying biodegradable osteosyntheses avoids the disadvantages of titanium osteosyntheses. However, foreign-body reactions remain a major concern and evidence of complete resorption is lacking. This study compared the physico-chemical properties, histological response and radiographs of four copolymeric biodegradable osteo-synthesis systems in a goat model with 48-months follow-up. The systems were implanted subperiosteally in both tibia and radius of 12 Dutch White goats. The BioSorb FX [poly(70LLA-co-30DLLA)], Inion CPS [poly([70–78.5] LLA-co-[16–24]DLLA-co-4TMC)], SonicWeld Rx [poly(DLLA)], LactoSorb [poly(82LLA-co-18GA)] systems and a negative control were randomly implanted in each extremity. Samples were assessed at 6-, 12-, 18-, 24-, 36-, and 48-month follow-up. Surface topography was performed using scanning electron microscopy (SEM). Differential scanning calorimetry and gel permeation chromatography were performed on initial and explanted samples. Histological sections were systematically assessed by two blinded researchers using (polarized) light microscopy, SEM and energy-dispersive X-ray analysis. The SonicWeld Rx system was amorphous while the others were semi-crystalline. Foreign-body reactions were not observed during the complete follow-up. The SonicWeld Rx and LactoSorb systems reached bone percentages of negative controls after 18 months while the BioSorb Fx and Inion CPS systems reached these levels after 36 months. The SonicWeld Rx system showed the most predictable degradation profile. All the biodegradable systems were safe to use and well-tolerated (i.e., complete implant replacement by bone, no clinical or histological foreign body reactions, no [sterile] abscess formation, no re-interventions needed), but nanoscale residual polymeric fragments were observed at every system’s assessment.

To fabricate artificial nerves with tissue engineering methods

Objective: To fabricate artificial nerves with tissue engineering methods in vitro. Methods: Schwann cells (SCs) were cultured and seeded on polyglactin 910 fibers wrapped by biomembrane coated with rat tail glue and laminin for 2 weeks. The absorbability on the scaffolds, growth and migration of SCs were assessed with a light microscope, a scanning electron microscope and a transmission electron microscope. Results: SCs could migrate and proliferate on polyglactin 910 fibers. They were well distributed between scaffolds and absorbed on surface of scaffolds and formed a bungner band, on which SCs produced more matrices. SCs seeded on the biomembrane could also grow well. Axon regeneration in the distal nerve stump was observed at 8 weeks. Conclusions: Adult SCs can be expanded on coated fibers and biomembrane. Three dimensional scaffold of SCs has the basic characteristics of artificial nerves. These findings offer a novel method to fabricate artificial nerves with tissue engineering methods for repairing defected long nerves.

Calcium citrate： a new biomaterial that can enhance bone formation in situ

Objective： To investigate the effect of a new biomaterial combining calcium citrate and recombinant human bone morphogenetic protein-2 （rhBMP-2） on bone regeneration in a bone defect rabbit model. Methods： Totally 30 male New Zealand white rabbits were randomly and equally divided into calcium citraterhBMP-2 （CC-rhBMP-2） group and rhBMP-2 only group. Two 10 ram-long and 5 ram-deep bone defects were respectively created in the left and right femoral condyles of the rabbits. Subsequently 5 pellets of calcium citrate （10 mg） combined with rhBMP-2 （2 rag） or rhBMP-2 alone were implanted into the bone defects and compressed with cotton swab. Bone granules were obtained at 2, 4 and 6 weeks after procedure and received histological analysis. LSD t-test and a subsequent t-test were adopted for statistical analysis. Results： Histomorphometric analysis revealed newlyformed bones, and calcium citrate has been absorbed in the treatment group. The percent of newly formed bone area in femoral condyle in control group and CC-rhBMP-2 group was respectively 31.73%±1.26% vs 48.21%±2.37% at 2 weeks; 43.40%±1.65% vs 57.32%±1.47% at 4 weeks, and 51.32%±7.80% vs 66.74%±4.05% at 6 weeks （P〈0.05 for all）. At 2 weeks, mature cancellous bone was observed to be already formed in the treatment group. Conclusion： From this study, it can be concluded that calcium citrate combined with rhBMP-2 signifcantly enhances bone regeneration in bone defects. This synthetic gelatin matrix stimulates formation of new bone and bone marrow in the defect areas by releasing calcium ions.

Role of precoating in artificial vessel endothelialization

As the progress of vascular surgery, artificial vessels have become the substitute for large and middle diameter vessels but have not for small diameter ones owing to thrombogenesis and occlusion within a short period of time after being applied. Artificial vessel endothelialization is one of the ideal methods to resolve such issue and has been improved continuously since Herring in 1978 put forward this term in the first time and utilized vascular endothelial cells (ECs) harvested from living animals to perform the test of artificial vessel endothelialization. However, human endothelial cells show little adhesion to the currently available vascular graft materials and some expanded polytetrafluoroethylene (ePTFE) grafts have shown only 10%+/-7% endothelial cell attachment rate (ECA, ie, attachment of ECs when incubated in vitro). Moreover, when the graft is exposed to pulsatile blood flow, a high proportion of cells are washed off from the lumen. Maximum cell loss occurs in the first 30-45 min after exposure to pulsatile flow, with up to 70% of cells lost. After that, a slower exponential loss occurs over the next 24 h. The lack of retention of cells could be partly overcome by sodding, but other techniques, involving engineering the lumen to improve ECA and endothelial cell retention rate (ECR, ie, retention of ECs when the grafts are exposed to pulsatile flow) have been developed. These include shear stress preconditioning, electrostatic charging and, above all, most successfully to date, precoating with EC specific adhesive glues that are mostly found in the extracellular basement membrane of blood vessels. The commonest are chemical coatings, preclotting, chemical bonding, and surface modifications.