Acta Biomaterialia最新文献

{"title":"Lipopolymer/siRNA complexes engineered for optimal molecular and functional response with chemotherapy in FLT3-mutated acute myeloid leukemia","authors":"Aysha S. Ansari ,&nbsp;Cezary Kucharski ,&nbsp;Remant KC ,&nbsp;Daniel Nisakar ,&nbsp;Ramea Rahim ,&nbsp;Xiaoyan Jiang ,&nbsp;Joseph Brandwein ,&nbsp;Hasan Uludağ","doi":"10.1016/j.actbio.2024.08.053","DOIUrl":"10.1016/j.actbio.2024.08.053","url":null,"abstract":"<div><div>Approximately 25% of newly diagnosed AML patients display an internal tandem duplication (ITD) in the <em>fms-like tyrosine kinase 3</em> (<em>FLT3</em>) gene. Although both multi-targeted and FLT3 specific tyrosine kinase inhibitors (TKIs) are being utilized for clinical therapy, drug resistance, short remission periods, and high relapse rates are challenges that still need to be tackled. RNA interference (RNAi), mediated by short interfering RNA (siRNA), presents a mechanistically distinct therapeutic platform with the potential of personalization due to its gene sequence-driven mechanism of action. This study explored the use of a non-viral approach for delivery of FLT3 siRNA (siFLT3) in FLT3-ITD positive AML cell lines and primary cells as well as the feasibility of combining this treatment with drugs currently used in the clinic. Treatment of AML cell lines with FLT3 siRNA nanocomplexes resulted in prominent reduction in cell proliferation rates and induction of apoptosis. Quantitative analysis of relative mRNA transcript levels revealed downregulation of the FLT3 gene, which was accompanied by a similar decline in FLT3 protein levels. Moreover, an impact on leukemic stem cells was observed in a small pool of primary AML samples through significantly reduced colony numbers. An absence of a molecular response post-treatment with lipopolymer/siFLT3 complexes in peripheral blood mononuclear cells, obtained from healthy individuals, denoted a passive selectivity of the complexes towards malignant cells. The effect of combining lipopolymer/siFLT3 complexes with daunorubucin and FLT3 targeting TKI gilteritinib led to a significant augmentation of anti-leukemic activity. These findings demonstrate the promising potential of RNAi implemented with lipopolymer complexes for AML molecular therapy. The study prospectively supports the addition of RNAi therapy to current treatment modalities available to target the heterogeneity prevalent in AML.</div></div><div><h3>Statement of significance</h3><div>We show that a clinically validated target, the <em>FLT3</em> gene, can be eradicated in leukemia cells using non-viral RNAi. We validated these lipopolymers as effective vehicles to deliver nucleic acids to leukemic cells. The potency of the lipopolymers was superior to that of the ‘gold-standard’ delivery agent, lipid nanoparticles (LNPs), which are not effective in leukemia cells at clinically relevant doses. Mechanistic studies were undertaken to probe structure-function relationships for effective biomaterial formulations. Cellular and molecular responses to siRNA treatment have been characterized in cell models, including leukemia patient-derived cells. The use of the siRNA therapy with clinically used chemotherapy was demonstrated.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"188 ","pages":"Pages 297-314"},"PeriodicalIF":9.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A photo-modulated nitric oxide delivering hydrogel for the accelerated healing of biofilm infected chronic wounds","authors":"Huifang Ma ,&nbsp;Tengjiao Wang ,&nbsp;Gangfeng Li ,&nbsp;Jiaheng Liang ,&nbsp;Jianhong Zhang ,&nbsp;Yang Liu ,&nbsp;Wenbin Zhong ,&nbsp;Peng Li","doi":"10.1016/j.actbio.2024.09.017","DOIUrl":"10.1016/j.actbio.2024.09.017","url":null,"abstract":"<div><div>Biofilm infection and impaired healing of chronic wounds are posing tremendous challenges in clinical practice. In this study, we presented a versatile antimicrobial hydrogel capable of delivering nitric oxide (NO) in a controllable manner to dissipate biofilms, eliminate microorganisms, and promote the healing of chronic wounds. This hydrogel was constructed by Schiff-base crosslinking of oxidized dextran and antimicrobial peptide ε-poly-lysine, further encapsulating photothermal nanoparticles bearing NO donor. This hydrogel could continuously and slowly release NO, effectively dissipating biofilms, and promoting the proliferation of mouse fibroblasts and the migration of endothelial cells. Upon exposure to NIR laser irradiation, the hydrogel generated hyperthermia and rapidly released NO, resulting in the efficient elimination of a broad spectrum of drug-resistant Gram-positive/negative bacterial and fungal biofilms through the synergistic effects of NO, photothermal therapy, and the antibacterial peptide. Notably, the hydrogel demonstrated exceptional <em>in vivo</em> therapeutic outcomes in accelerating the healing process of mice diabetic wounds infected with methicillin-resistant <em>Staphylococcus aureus</em> by successfully eliminating biofilm infection, regulating inflammation, and facilitating angiogenesis and collagen deposition. Overall, this proposed hydrogel shows great promise in accommodating the various demands of the complex repair process of chronic wounds infected with biofilms.</div></div><div><h3>Statement of significance</h3><div>The presence of biofilm infections and underlying dysfunctions in the healing process made chronic wound become stuck in the inflammation stage and difficult to heal. This work developed a NIR laser-modulated three-stage NO-releasing versatile antimicrobial hydrogel (DEPN) exhibiting good therapeutic efficacy for chronic wound. This DEPN hydrogel could inherently and slowly released NO to disperse biofilm. Upon NIR laser irradiation, the DEPN hydrogel generated hyperthermia and induced a rapid burst release of NO effectively eliminating a broad spectrum of drug-resistant bacterial and fungal biofilms. Subsequently, the DEPN hydrogel continually release NO slowly to promote the tissue remolding. This DEPN hydrogel displays great potential in treatment of chronic wounds infected with biofilm.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"188 ","pages":"Pages 169-183"},"PeriodicalIF":9.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A viscoelastic constitutive framework for aging muscular and elastic arteries","authors":"Will Zhang ,&nbsp;Majid Jadidi ,&nbsp;Sayed Ahmadreza Razian ,&nbsp;Gerhard A. Holzapfel ,&nbsp;Alexey Kamenskiy ,&nbsp;David A. Nordsletten","doi":"10.1016/j.actbio.2024.09.021","DOIUrl":"10.1016/j.actbio.2024.09.021","url":null,"abstract":"<div><div>The evolution of arterial biomechanics and microstructure with age and disease plays a critical role in understanding the health and function of the cardiovascular system. Accurately capturing these adaptative processes and their effects on the mechanical environment is critical for predicting arterial responses. This challenge is exacerbated by the significant differences between elastic and muscular arteries, which have different structural organizations and functional demands. In this study, we aim to shed light to these adaptive processes by comparing the viscoelastic mechanics of autologous thoracic aortas (TA) and femoropopliteal arteries (FPA) in different age groups. We have extended our fractional viscoelastic framework, originally developed for FPA, to both types of arteries. To evaluate this framework, we analyzed experimental mechanical data from TA and FPA specimens from 21 individuals aged 13 to 73 years. Each specimen was subjected to a multi-ratio biaxial mechanical extension and relaxation test complemented by bidirectional histology to quantify the structural density and microstructural orientations. Our new constitutive model accurately captured the mechanical responses and microstructural differences of the tissues and closely matched the experimentally measured densities. It was found that the viscoelastic properties of collagen and smooth muscle cells (SMCs) in both the FPA and TA remained consistent with age, but the viscoelasticity of the SMCs in the FPA was twice that of the TA. Additionally, changes in collagen nonlinearity with age were similar in both TA and FPA. This model provides valuable insights into arterial mechanophysiology and the effects of pathological conditions on vascular biomechanics.</div></div><div><h3>Statement of significance</h3><div>Developing durable treatments for arterial diseases necessitates a deeper understanding of how mechanical properties evolve with age in response to mechanical environments. In this work, we developed a generalized viscoelastic constitutive model for both elastic and muscular arteries and analyzed both the thoracic aorta (TA) and the femoropopliteal artery (FPA) from 21 donors aged 13 to 73. The derived parameters correlate well with histology, allowing further examination of how viscoelasticity evolves with age. Correlation between the TA and FPA of the same donors suggest that the viscoelasticity of the FPA may be influenced by the TA, necessitating more detailed analysis. In summary, our new model proves to be a valuable tool for studying arterial mechanophysiology and exploring pathological impacts.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"188 ","pages":"Pages 223-241"},"PeriodicalIF":9.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging microfluidic gut-on-a-chip systems for drug development","authors":"Xueqi Wang ,&nbsp;Yuzhuo Zhu ,&nbsp;Zhaoming Cheng ,&nbsp;Chuanjun Zhang ,&nbsp;Yumeng Liao ,&nbsp;Boshi Liu ,&nbsp;Di Zhang ,&nbsp;Zheng Li ,&nbsp;Yuxin Fang","doi":"10.1016/j.actbio.2024.09.012","DOIUrl":"10.1016/j.actbio.2024.09.012","url":null,"abstract":"<div><div>The gut is a vital organ that is central to the absorption and metabolic processing of orally administered drugs. While there have been many models developed with the goal of studying the absorption of drugs in the gut, these models fail to adequately recapitulate the diverse, complex gastrointestinal microenvironment. The recent emergence of microfluidic organ-on-a-chip technologies has provided a novel means of modeling the gut, yielding radical new insights into the structure of the gut and the mechanisms through which it shapes disease, with key implications for biomedical developmental efforts. Such organ-on-a-chip technologies have been demonstrated to exhibit greater cost-effectiveness, fewer ethical concerns, and a better ability to address inter-species differences in traditional animal models in the context of drug development. The present review offers an overview of recent developments in the reconstruction of gut structure and function <em>in vitro</em> using microfluidic gut-on-a-chip (GOC) systems, together with a discussion of the potential applications of these platforms in the context of drug development and the challenges and future prospects associated with this technology.</div></div><div><h3>Statement of significance</h3><div>This paper outlines the characteristics of the different cell types most frequently used to construct microfluidic gut-on-a-chip models and the microfluidic devices employed for the study of drug absorption. And the applications of gut-related multichip coupling and disease modelling in the context of drug development is systematically reviewed. With the detailed summarization of microfluidic chip-based gut models and discussion of the prospective directions for practical application, this review will provide insights to the innovative design and application of microfluidic gut-on-a-chip for drug development.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"188 ","pages":"Pages 48-64"},"PeriodicalIF":9.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mussel-inspired bifunctional coating for long-term stability of oral implants","authors":"Mengmeng Wang ,&nbsp;Jie Li ,&nbsp;Mengqian Geng ,&nbsp;Zhen Yang ,&nbsp;Aiwen Xi ,&nbsp;Yingying Yu ,&nbsp;Bin Liu ,&nbsp;Franklin R. Tay ,&nbsp;Yaping Gou","doi":"10.1016/j.actbio.2024.09.010","DOIUrl":"10.1016/j.actbio.2024.09.010","url":null,"abstract":"<div><div>Peri-implantitis and osseointegration failure present considerable challenges to the prolonged stability of oral implants. To address these issues, there is an escalating demand for a resilient implant surface coating that seamlessly integrates antimicrobial features to combat bacteria-induced peri‑implantitis, and osteogenic properties to promote bone formation. In the present study, a bio-inspired poly(amidoamine) dendrimer (DA-PAMAM-NH₂) is synthesized by utilizing a mussel protein (DA) known for its strong adherence to various materials. Conjugating DA with PAMAM-NH₂, inherently endowed with antibacterial and osteogenic properties, results in a robust and multifunctional coating. Robust adhesion between DA-PAMAM-NH₂ and the titanium alloy surface is identified using confocal laser scanning microscopy (CLSM) and attenuated total reflectance-infrared (ATR-IR) spectroscopy. Following a four-week immersion of the coated titanium alloy surface in simulated body fluid (SBF), the antimicrobial activity and superior osteogenesis of the DA-PAMAM-NH₂-coated surface remain stable. In contrast, the bifunctional effects of the PAMAM-NH₂-coated surface diminish after the same immersion period. In vivo animal experiments validate the enduring antimicrobial and osteogenic properties of DA-PAMAM-NH₂-coated titanium alloy implants, significantly enhancing the long-term stability of the implants. This innovative coating holds promise for addressing the multifaceted challenges associated with peri‑implantitis and osseointegration failure in titanium-based implants.</div></div><div><h3>Statement of significance</h3><div>Prolonged stability of oral implants remains a clinically-significant challenge. Peri-implantitis and osseointegration failure are two important contributors to the poor stability of oral implants. The present study developed a mussel-bioinspired poly(amidoamine) dendrimer (DA-PAMAM-NH₂) for a resilient implant surface coating that seamlessly integrates antimicrobial features to combat bacteria-induced peri‑implantitis, and osteogenic properties to promote bone formation to extend the longevity of oral implants.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"188 ","pages":"Pages 138-156"},"PeriodicalIF":9.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D-ink-extruded titanium scaffolds with porous struts and bioactive supramolecular polymers for orthopedic implants","authors":"John P. Misiaszek ,&nbsp;Nicholas A. Sather ,&nbsp;Alyssa M. Goodwin ,&nbsp;Hogan J. Brecount ,&nbsp;Steven S. Kurapaty ,&nbsp;Jacqueline E. Inglis ,&nbsp;Erin L. Hsu ,&nbsp;Samuel I. Stupp ,&nbsp;Stuart R. Stock ,&nbsp;David C. Dunand","doi":"10.1016/j.actbio.2024.09.004","DOIUrl":"10.1016/j.actbio.2024.09.004","url":null,"abstract":"<div><div>Porous titanium addresses the longstanding orthopedic challenges of aseptic loosening and stress shielding. This work expands on the evolution of porous Ti with the manufacturing of hierarchically porous, low stiffness, ductile Ti scaffolds via direct-ink write (DIW) extrusion and sintering of inks containing Ti and NaCl particles. Scaffold macrochannels were filled with a subtherapeutic dose of recombinant bone morphogenetic protein-2 (rhBMP-2) alone or co-delivered within a bioactive supramolecular polymer slurry (SPS) composed of peptide amphiphile nanofibrils and collagen, creating four treatment conditions (Ti struts: microporous vs. fully dense; BMP-2 alone or with SPS). The BMP-2-loaded scaffolds were implanted bilaterally across the L4 and L5 transverse processes in a rat posterolateral lumbar fusion model. In-vivo bone growth in these scaffolds is evaluated with synchrotron X-ray computed microtomography (µCT) to study the effects of strut microporosity and added biological signaling agents on the bone formation response. Optical and scanning electron microscopy confirms the ∼100 µm space-holder micropore size, high-curvature morphology, and pore fenestrations within the struts. Uniaxial compression testing shows that the microporous strut scaffolds have low stiffness and high ductility. A significant promotion in bone formation was observed for groups utilizing the SPS, while no significant differences were found for the scaffolds with the incorporation of micropores.</div></div><div><h3>Statement of significance</h3><div>By 2050, the anticipated number of people aged 60 years and older worldwide is anticipated to double to 2.1 billion. This rapid increase in the geriatric population will require a corresponding increase in orthopedic surgeries and more effective materials for longer indwelling times. Titanium alloys have been the gold standard of bone fusion and fixation, but their use has longstanding limitations in bone-implant stiffness mismatch and insufficient osseointegration. We utilize 3D-printing of titanium with NaCl space holders for large- and small-scale porosity and incorporate bioactive supramolecular polymers into the scaffolds to increase bone growth. This work finds no significant change in bone ingrowth via space-holder-induced microporosity but significant increases in bone ingrowth via the bioactive supramolecular polymers in a rat posterolateral fusion model.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"188 ","pages":"Pages 446-459"},"PeriodicalIF":9.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of pediatric porcine pulmonary valves as a model for tissue engineered heart valves","authors":"Shouka Parvin Nejad ,&nbsp;Bahram Mirani ,&nbsp;Zahra Mirzaei ,&nbsp;Craig A. Simmons","doi":"10.1016/j.actbio.2024.08.050","DOIUrl":"10.1016/j.actbio.2024.08.050","url":null,"abstract":"<div><div>Heart valve tissue engineering holds the potential to transform the surgical management of congenital heart defects affecting the pediatric pulmonary valve (PV) by offering a viable valve replacement. While aiming to recapitulate the native valve, the minimum requirement for tissue engineered heart valves (TEHVs) has historically been adequate mechanical function at implantation. However, long-term in situ functionality of TEHVs remains elusive, suggesting that a closer approximation of the native valve is required. The realization of biomimetic engineered pediatric PV is impeded by insufficient characterization of healthy pediatric tissue. In this study, we comprehensively characterized the planar biaxial tensile behaviour, extracellular matrix (ECM) composition and organization, and valvular interstitial cell (VIC) phenotypes of PVs from piglets to provide benchmarks for TEHVs. The piglet PV possessed an anisotropic and non-linear tension-strain profile from which material constants for a predictive constitutive model were derived. The ECM of the piglet PV possessed a trilayer organization populated by collagen, glycosaminoglycans, and elastin. Biochemical quantification of ECM content normalized to wet weight and DNA content of PV tissue revealed homogeneous distribution across sampled regions of the leaflet. Finally, VICs in the piglet PV were primarily quiescent vimentin-expressing fibroblasts, with a small proportion of activated α-smooth muscle actin-expressing myofibroblasts. Overall, piglet PV properties were consistent with those reported anecdotally for pediatric human PVs and distinct from those of adult porcine and human PVs, supporting the utility of the properties determined here to inform the design of tissue engineered pediatric PVs.</div></div><div><h3>Statement of significance</h3><div>Heart valve tissue engineering has the potential to transform treatment for children born with defective pulmonary valves by providing living replacement tissue that can grow with the child. The design of tissue engineered heart valves is best informed by native valve properties, but native pediatric pulmonary valves have not been fully described to date. Here, we provide comprehensive characterization of the planar biaxial tensile behaviour, extracellular matrix composition and organization, and valvular interstitial cell phenotypes of pulmonary valves from piglets as a model for the native human pediatric valve. Together, these findings provide standards that inform engineered heart valve design towards generation of biomimetic pediatric pulmonary valves.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"188 ","pages":"Pages 242-252"},"PeriodicalIF":9.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induced pluripotent stem cell-derived neural stem cells promote bone formation in mice with calvarial defects","authors":"Yukari Shiwaku ,&nbsp;Hiroko Okawa ,&nbsp;Ikuro Suzuki ,&nbsp;Susumu Sakai ,&nbsp;Hiroshi Egusa ,&nbsp;Osamu Suzuki","doi":"10.1016/j.actbio.2024.08.054","DOIUrl":"10.1016/j.actbio.2024.08.054","url":null,"abstract":"<div><div>Nerve-derived factors have attracted attention in bone regeneration therapy due to their ability to promote bone regeneration and nerve innervation. Mesenchymal stem cells transported to target sites promote osteogenesis. However, there are few reports on the effects of neural stem cells on bone regeneration. Therefore, the aim of this study was to investigate the role of neural stem cells in osteogenesis. Here, embryoid bodies (EB) or primary neurospheres (1NS) were generated using mouse induced pluripotent stem cells (iPS cells), which were then seeded onto gelatin (Gel) sponges. The seeded Gel sponges were then transplanted into mouse calvarial bone defects. We noted that 1NS-seeded Gel promoted bone regeneration and the presence of tartrate-resistant acid phosphatase (TRAP)-positive cells, whereas the EB-seeded Gel did not. RNA-sequencing of the 1NS-seeded and EB seeded Gels showed an upregulation of the transforming growth factor (TGF)-β signaling pathway in the 1NS-seeded Gel group. Immunostaining confirmed the presence of Id3 positive cells in mice with bone defects treated with the 1NS-seeded Gel. These findings suggest that the transplantation of neural stem cells may contribute to the promotion of bone regeneration.</div></div><div><h3>Statement of significance</h3><div>This study aimed to investigate whether neural stem cells, when seeded in Gel sponges, promoted bone regeneration. It has been well documented that bone is tightly linked with the nervous systems. Bioscaffolds comprising factors that promote innervation and bone regeneration have been investigated for use in bone therapy. However, there is limited research on the use of neural stem cells for promoting bone formation. To assess this relationship, we conducted both <em>in vivo</em> and <em>in vitro</em> assays to determine whether neural stem cells promoted bone formation. We noted that 1NS-seeded Gel sponges promoted bone formation significantly in mice with calvarial defects after 4 weeks. This study provides a novel approach of neural stem cells for bone therapy.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"188 ","pages":"Pages 93-102"},"PeriodicalIF":9.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142147079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, characterization, and surface modification of degradable polar hydrophobic ionic polyurethane nanoparticles for the delivery of therapeutics to vascular tissue","authors":"Chantal M. Trepanier ,&nbsp;Jonathan Rubianto ,&nbsp;Jonah Burke-Kleinman ,&nbsp;Ryan Appings ,&nbsp;Michelle P. Bendeck ,&nbsp;J. Paul Santerre","doi":"10.1016/j.actbio.2024.09.024","DOIUrl":"10.1016/j.actbio.2024.09.024","url":null,"abstract":"<div><div>Degradable polar hydrophobic ionic polyurethanes (D-PHI) are an emerging class of biomaterials with particular significance for blood-contacting applications due to their immunomodulatory effects and highly customizable block chemistry. In this manuscript, D-PHI polymer was formulated as a nanoparticle excipient for the first time by inverse emulsion polymerization. The nanoparticles were optimized with consideration of diameter, surface charge, size variability, and yield as a delivery vehicle for a custom vascular therapeutic peptide. A layer-by-layer (LBL) surface modification technique using poly-L-lysine was integrated within the nanoparticle design to optimize therapeutic loading efficiency. Solvent pH played a pivotal role in emulsion micelle formation, LBL polymer secondary structure, and the polymer functional group interactions critical for high therapeutic loading. The resulting nanoparticle platform met target size (200 ± 20 nm), polydispersity (&lt;0.07), and storage stability standards, was nontoxic, and did not affect therapeutic peptide bioactivity <em>in vitro.</em> Surface-modified D-PHI nanoparticles can be reproducibly manufactured at low cost, generating a highly customizable excipient platform suitable for delivery of biomolecular therapeutics. These nanoparticles have potential applications in vascular drug delivery via localized infusion, drug eluting stents, and drug-coated angioplasty balloons.</div></div><div><h3>Statement of significance</h3><div>Nanoscale excipients have become critical in the delivery of many therapeutics to enhance drug stability and targeted biodistribution through careful design of nanoparticle composition, surface chemistry, and size. This manuscript describes the development of a nanoparticle excipient derived from an immunomodulatory degradable polar hydrophobic ionic polyurethane, in combination with a layer-by-layer surface modification approach utilizing poly-L-lysine, to transport a mimetic peptide targeting smooth muscle cell migration in vascular disease. The nanoparticle platform draws on the effect of pH to maximize drug loading and tailor particle properties. The low cost and easily reproducible system presents a highly customizable platform that can be adapted for therapeutic delivery across a wide range of clinical indications.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"188 ","pages":"Pages 184-196"},"PeriodicalIF":9.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adoptive transfer of immunomodulatory macrophages reduces the pro-inflammatory microenvironment and increases bone formation on titanium implants","authors":"Lais Morandini ,&nbsp;Tyler Heath ,&nbsp;Luke S. Sheakley ,&nbsp;Derek Avery ,&nbsp;Melissa Grabiec ,&nbsp;Michael Friedman ,&nbsp;Rebecca K. Martin ,&nbsp;Jonathan Boyd ,&nbsp;Rene Olivares-Navarrete","doi":"10.1016/j.actbio.2024.09.011","DOIUrl":"10.1016/j.actbio.2024.09.011","url":null,"abstract":"<div><div>Macrophages play a central role in orchestrating the inflammatory response to implanted biomaterials and are sensitive to changes in the chemical and physical characteristics of the implant. Macrophages respond to biological, chemical, and physical cues by polarizing into pro-inflammatory (M1) or anti-inflammatory (M2) states. We previously showed that rough-hydrophilic titanium (Ti) implants skew macrophage polarization towards an anti-inflammatory phenotype and increase mesenchymal stem cell (MSC) recruitment and bone formation around the implant. In the present study, we aimed to investigate whether the adoptive transfer of macrophages in different polarization states would alter the inflammatory microenvironment and improve biomaterial integration in macrophage-competent and macrophage-ablated mice. We found that ablating macrophages increased the presence of neutrophils, reduced T cells and MSCs, and compromised the healing and biomaterial integration process. These effects could not be rescued with adoptive transfer of naïve or polarized macrophages. Adoptive transfer of M1 macrophages into macrophage-competent mice increased inflammatory cells and inflammatory microenvironment, resulting in decreased bone-to-implant contact. Adoptive transfer of M2 macrophages into macrophage-competent mice reduced the pro-inflammatory environment in the peri‑implant tissue and increased bone-to-implant contact. Taken together, our results show the importance of macrophages in controlling and modulating the inflammatory process in response to implanted biomaterials and suggest they can be used to improve outcomes following biomaterial implantation.</div></div><div><h3>Statement of significance</h3><div>Macrophages are central in orchestrating the inflammatory response to implanted biomaterials and are sensitive to biomaterial chemical and physical characteristics. Our study shows that a deficiency of macrophages results in prolonged inflammation and abolishes bone-biomaterial integration. Adoptive transfer of immunomodulatory macrophages into macrophage-competent mice reduced the inflammatory environment and increased bone-implant contact.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"188 ","pages":"Pages 432-445"},"PeriodicalIF":9.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}