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 applicati...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.展开更多
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 s...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.展开更多
Treatment of intracranial gliomas has increasingly favored minimally invasive surgery,with a growing focus on leveraging microrobots for efficient drug delivery while overcoming the impact of body fluids.Inspired by h...Treatment of intracranial gliomas has increasingly favored minimally invasive surgery,with a growing focus on leveraging microrobots for efficient drug delivery while overcoming the impact of body fluids.Inspired by honeybee stingers,this study proposed a novel microspike robot.This robot firmly adhered to the tissue surface,enabling direct drug delivery from a hydrogel on its back into the targeted tissue via microspikes.The drug delivery rate was influenced by temperature and could be controlled by an alternating magnetic field.Microrobots could be delivered rapidly through a clinical Ommaya reservoir into the postoperative cavity or ventricle of the skull.The microrobot could be actuated for adhesion and retrieval,with its motion posture and trajectory highly precisely controlled by external magnetic fields.Biological experiments confirmed the excellent biocompatibility and biosafety of the microspike robot and demonstrated its effectiveness in treating gliomas by loading unconventional therapeutic drugs.The proposed microspike robot has significant potential for long-term drug delivery to target gliomas and other future clinical applications.展开更多
Microneedles(MNs)are an innovative and viable option for drug delivery that offer the distinct advantages of minimal invasiveness,painlessness,stable drug loading,efficient drug permeation,and biocompatibility.MNs wer...Microneedles(MNs)are an innovative and viable option for drug delivery that offer the distinct advantages of minimal invasiveness,painlessness,stable drug loading,efficient drug permeation,and biocompatibility.MNs were first used to penetrate the skin surface and facilitate transcutaneous drug delivery with great success.Recent applications of MNs have extended to non-transdermal drug delivery,specifically,to various tissues and organs.This review captures the fabrication methods for MNs,discusses advanced design strategies for achieving controlled drug release,and summarizes current MN applications in delivering multiple therapeutic agents to the cardiovascular,digestive(e.g.,oral cavity),reproductive,and central nervous systems.The findings in this review would contribute toward the improved designs of MN systems that can be modified according to purpose,including material selection,structural design,choice of fabrication methods,and tissue considerations,to determine the optimal therapeutic regimen for the target treatment area.展开更多
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 relatio...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].展开更多
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...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.展开更多
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 an...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.展开更多
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-bifunc...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.展开更多
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...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.展开更多
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 material...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 fix<span style="font-family:Verdana;">ation in orthognathic surgery and craniofacial trauma. For this study, 30 conventional 2.0</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">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 <</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">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.</span>展开更多
Catalytic biomaterials are biocompatible materials with catalytic activity at the nano-,micro-,and macroscopic scales.These materials can trigger specific biochemical or chemical reactions in situ within a targeted ph...Catalytic biomaterials are biocompatible materials with catalytic activity at the nano-,micro-,and macroscopic scales.These materials can trigger specific biochemical or chemical reactions in situ within a targeted physiological environment,thereby enabling therapeutic functions.1 Compared to conventional biomaterials,catalytic biomaterials exert therapeutic effects through the intermediates or products of catalytic reactions.This eliminates the need for small-molecule drugs that often cause adverse side effects,ensuring inherently low toxicity.展开更多
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...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.展开更多
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 chan...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.展开更多
The rational design of molecules with the desired functionality presents a significant challenge in chemistry.Moreover,it is worth noting that making chemicals safe and sustainable is crucial to bringing them to the m...The rational design of molecules with the desired functionality presents a significant challenge in chemistry.Moreover,it is worth noting that making chemicals safe and sustainable is crucial to bringing them to the market.To address this,we propose a novel deep learning framework developed explicitly for inverse design of molecules with both functionality and biocompatibility.This innovative approach comprises two predictive models and one generative model,facilitating the targeted screening of novel molecules from created virtual chemical space.Our method’s versatility is highlighted in the inverse design process,where it successfully generates molecules with specified motifs or composition,discovers synthetically accessible molecules,and jointly targets functional and safe properties beyond the training regime.The utility of this method is demonstrated in its ability to design ionic liquids(ILs)with enhanced antibacterial properties and reduced cytotoxicity,addressing the issue of balancing functionality and biocompatibility in molecular design.展开更多
Effective reconstruction of large bone defects,particularly in thickness,remains one of the major challenges in orthopedic and dental fields.We previously produced an Escherichia coli-based industrial-scale GMP-grade ...Effective reconstruction of large bone defects,particularly in thickness,remains one of the major challenges in orthopedic and dental fields.We previously produced an Escherichia coli-based industrial-scale GMP-grade recombinant human bone morphoge-netic protein-2(E-rhBMP-2)and showed that the combination of E-rhBMP-2 with beta-tricalcium phosphate(β-TCP/E-rhBMP-2)can effectively promote bone reconstruction.However,the lim-ited mechanical strength and poor morphology retention ofβ-TCP granules are key points that need optimization to obtain more effective grafts and further expand its clinical applications.Therefore,we combinedβ-TCP/E-rhBMP-2 with fibrin gel to enhance its mechanical properties and usability for vertical bone regeneration.We investigated the mechanical properties and vertical bone regeneration effects of the materials applied,with or with-out fibrin containing E-rhBMP-2,in a calvarial defect model in mice.Compression tests were conducted to assess the initial stability of the materials.Scanning electron microscopy and Fourier transform infrared spectroscopy were conducted to characterize the presence of fibrin on the scaffold.After 4 and 12 weeks of implantation,micro-computed tomography and histological and immunofluorescent analyses were performed to assess the morphology and volume of the newly formed bone.The fibrin-containing groups had signifi-cantly higher initial mechanical strength and higher ability to maintain their morphology in vivo compared to the counterparts without fibrin.However,fibrin gel alone suppressed the bone formation ability ofβ-TCP/E-rhBMP-2 whereas the presence of high doses of E-rhBMP-2 in fibrin gel resulted in material resorption and enhanced new bone formation.In conclusion,fibrin gel significantly improved the mechanical strength and surgical manageability of theβ-TCP/E-rhBMP-2 scaffold,and the addition of E-rhBMP-2 to the fibrin gel further enhanced the vertical bone regeneration and initial structural integrity of the scaffold.展开更多
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...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.展开更多
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 ind...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.展开更多
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 ...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.展开更多
基金We thank the Conselho Nacional de Desenvolvimento Cientifico e Tecnológico(CNPq)Coordenacao de Aperfeicoamento de Pessoal Docente(CAPES-Edital Nanobiotecnologia 2008) Fundacao de AmparoaPesquisa do Estado do Rio de Janeiro(FAPERJ)for the financial support and fellowships.
文摘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.
基金supported by the Key Research Projects of Universities of Henan Province,No.21A320064 (to XS)the National Key Research and Development Program of China,No.2021YFA1201504 (to LZ)+1 种基金the Strategic Priority Research Program of the Chinese Academy of Science,No.XDB36000000 (to CW)the National Natural Science Foundation of China,Nos.31971295,12374406 (both to LZ)。
文摘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.
基金supported by the National Key R&D Program of China(No.2023YFB4705600)the National Natural Science Foundation of China(Nos.U23A20342,62273331,61925307,and 61821005)+1 种基金the CAS Project for Young Scientists in Basic Research(No.YSBR-036)the CAS/SAFEA International Partnership Program for Creative Research Teams.
文摘Treatment of intracranial gliomas has increasingly favored minimally invasive surgery,with a growing focus on leveraging microrobots for efficient drug delivery while overcoming the impact of body fluids.Inspired by honeybee stingers,this study proposed a novel microspike robot.This robot firmly adhered to the tissue surface,enabling direct drug delivery from a hydrogel on its back into the targeted tissue via microspikes.The drug delivery rate was influenced by temperature and could be controlled by an alternating magnetic field.Microrobots could be delivered rapidly through a clinical Ommaya reservoir into the postoperative cavity or ventricle of the skull.The microrobot could be actuated for adhesion and retrieval,with its motion posture and trajectory highly precisely controlled by external magnetic fields.Biological experiments confirmed the excellent biocompatibility and biosafety of the microspike robot and demonstrated its effectiveness in treating gliomas by loading unconventional therapeutic drugs.The proposed microspike robot has significant potential for long-term drug delivery to target gliomas and other future clinical applications.
基金financial support from the Beijing Natural Science Foundation(No.L234020)the National Natural Science Foundation of China(Nos.12472325 and 12272032)the 111 Project(No.B13003).
文摘Microneedles(MNs)are an innovative and viable option for drug delivery that offer the distinct advantages of minimal invasiveness,painlessness,stable drug loading,efficient drug permeation,and biocompatibility.MNs were first used to penetrate the skin surface and facilitate transcutaneous drug delivery with great success.Recent applications of MNs have extended to non-transdermal drug delivery,specifically,to various tissues and organs.This review captures the fabrication methods for MNs,discusses advanced design strategies for achieving controlled drug release,and summarizes current MN applications in delivering multiple therapeutic agents to the cardiovascular,digestive(e.g.,oral cavity),reproductive,and central nervous systems.The findings in this review would contribute toward the improved designs of MN systems that can be modified according to purpose,including material selection,structural design,choice of fabrication methods,and tissue considerations,to determine the optimal therapeutic regimen for the target treatment area.
基金Supported in part by phone-Poulenc Rorer Pharmaceuticals INC
文摘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].
基金supported by a grant from the National High Technology Research and Development Program of China (Program 863) (No. 2006AA02A124)
文摘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.
基金Supported by the Chengdu Municipal Medical Research Project(Grant Nos.2019005 and 2022014)Sichuan Provincial Cadres Health Research Project(Grant No.ChuanGanYan(2013-104)).
文摘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.
基金Supported by the National Natural Science Foundation of China and Huoyindong Education Foundation
文摘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.
文摘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.
文摘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 fix<span style="font-family:Verdana;">ation in orthognathic surgery and craniofacial trauma. For this study, 30 conventional 2.0</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">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 <</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">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.</span>
基金the financial support from the National Natural Science Foundation of China(Grant Nos.52102350)The Chenguang Program of the Shanghai Education Development Foundation and Shanghai Municipal Education Commissionthe Wenzhou Basic Scientific Research Project(Grant No.Y20230135).
文摘Catalytic biomaterials are biocompatible materials with catalytic activity at the nano-,micro-,and macroscopic scales.These materials can trigger specific biochemical or chemical reactions in situ within a targeted physiological environment,thereby enabling therapeutic functions.1 Compared to conventional biomaterials,catalytic biomaterials exert therapeutic effects through the intermediates or products of catalytic reactions.This eliminates the need for small-molecule drugs that often cause adverse side effects,ensuring inherently low toxicity.
基金supported by Trinity College Dublin(Trinity Research Doctorate Award).All figures were created with BioR ender.com.
文摘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.
基金Supported by the Natural Science Foundation of Fujian Province of China(No.2010J01291)
文摘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.
基金supported by the National Natural Science Foundation of China(22106025,22036002)the Introduced Innovative R&D Team Project under the“The Pearl River Talent Recruitment Program”of Guangdong Province(2019ZT08L387)+1 种基金the Basic and Applied Basic Research Foundation of Guangzhou,China(202201010541)the Guangdong Basic and Applied Basic Research Foundation(2022A1515111082).
文摘The rational design of molecules with the desired functionality presents a significant challenge in chemistry.Moreover,it is worth noting that making chemicals safe and sustainable is crucial to bringing them to the market.To address this,we propose a novel deep learning framework developed explicitly for inverse design of molecules with both functionality and biocompatibility.This innovative approach comprises two predictive models and one generative model,facilitating the targeted screening of novel molecules from created virtual chemical space.Our method’s versatility is highlighted in the inverse design process,where it successfully generates molecules with specified motifs or composition,discovers synthetically accessible molecules,and jointly targets functional and safe properties beyond the training regime.The utility of this method is demonstrated in its ability to design ionic liquids(ILs)with enhanced antibacterial properties and reduced cytotoxicity,addressing the issue of balancing functionality and biocompatibility in molecular design.
基金funded by Japan Society for the Promotion of Science KAKENHI(Grant Numbers JP24K21302,JP22K19625,JP23K24538,JP19K09649 and JP24K02626)by Japan Science and Technology Agency CREST(Grant Number JPMJCR22L5).
文摘Effective reconstruction of large bone defects,particularly in thickness,remains one of the major challenges in orthopedic and dental fields.We previously produced an Escherichia coli-based industrial-scale GMP-grade recombinant human bone morphoge-netic protein-2(E-rhBMP-2)and showed that the combination of E-rhBMP-2 with beta-tricalcium phosphate(β-TCP/E-rhBMP-2)can effectively promote bone reconstruction.However,the lim-ited mechanical strength and poor morphology retention ofβ-TCP granules are key points that need optimization to obtain more effective grafts and further expand its clinical applications.Therefore,we combinedβ-TCP/E-rhBMP-2 with fibrin gel to enhance its mechanical properties and usability for vertical bone regeneration.We investigated the mechanical properties and vertical bone regeneration effects of the materials applied,with or with-out fibrin containing E-rhBMP-2,in a calvarial defect model in mice.Compression tests were conducted to assess the initial stability of the materials.Scanning electron microscopy and Fourier transform infrared spectroscopy were conducted to characterize the presence of fibrin on the scaffold.After 4 and 12 weeks of implantation,micro-computed tomography and histological and immunofluorescent analyses were performed to assess the morphology and volume of the newly formed bone.The fibrin-containing groups had signifi-cantly higher initial mechanical strength and higher ability to maintain their morphology in vivo compared to the counterparts without fibrin.However,fibrin gel alone suppressed the bone formation ability ofβ-TCP/E-rhBMP-2 whereas the presence of high doses of E-rhBMP-2 in fibrin gel resulted in material resorption and enhanced new bone formation.In conclusion,fibrin gel significantly improved the mechanical strength and surgical manageability of theβ-TCP/E-rhBMP-2 scaffold,and the addition of E-rhBMP-2 to the fibrin gel further enhanced the vertical bone regeneration and initial structural integrity of the scaffold.
文摘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.
基金This work was supported by a grant from the National Natural Science Foundation of China （No. 81371702）.
文摘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.
文摘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.
