{"title":"DNA Aptamers That Bind to Alginate Hydrogels.","authors":"Ali Parvez, Dana A Baum","doi":"10.1021/acsbiomaterials.4c01436","DOIUrl":"10.1021/acsbiomaterials.4c01436","url":null,"abstract":"<p><p>Hydrogels have become common in wound treatment because they form very stable and biocompatible environments that promote healing. However, due to the highly porous hydrogel structure, any therapeutic added to these gels tends to diffuse quickly and impact delivery to the target site. Aptamers are short, single-stranded DNA or RNA sequences that bind specifically to a target, so aptamers that bind to hydrogels could serve as tags for therapeutics to prevent rapid diffusion and allow for extended delivery. An in vitro selection approach was developed to identify DNA aptamers for alginate hydrogels. Two DNA aptamers were shown to bind hydrogels ranging from 0.5 to 2% alginate and could be either encapsulated during gelation or introduced to preformed gels. Both aptamers also showed specificity for binding to alginate compared to agarose. To demonstrate the functional aspect of the aptamers as tethers for other biomolecules, both aptamers were conjugated to BSA. Aptamer-conjugated BSA was retained longer in the hydrogel during week-long diffusion studies both when encapsulated or introduced to preformed gels, which adds flexibility to how these aptamers can be deployed in a clinical setting.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"7507-7515"},"PeriodicalIF":5.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
T Braxton, K Lim, C Alcala-Orozco, H Joukhdar, J Rnjak-Kovacina, N Iqbal, T Woodfield, D Wood, C Brockett, X B Yang
{"title":"Mechanical and Physical Characterization of a Biphasic 3D Printed Silk-Infilled Scaffold for Osteochondral Tissue Engineering.","authors":"T Braxton, K Lim, C Alcala-Orozco, H Joukhdar, J Rnjak-Kovacina, N Iqbal, T Woodfield, D Wood, C Brockett, X B Yang","doi":"10.1021/acsbiomaterials.4c01865","DOIUrl":"10.1021/acsbiomaterials.4c01865","url":null,"abstract":"<p><p>Osteochondral tissue damage is a serious concern, with even minor cartilage damage dramatically increasing an individual's risk of osteoarthritis. Therefore, there is a need for an early intervention for osteochondral tissue regeneration. 3D printing is an exciting method for developing novel scaffolds, especially for creating biological scaffolds for osteochondral tissue engineering. However, many 3D printing techniques rely on creating a lattice structure, which often demonstrates poor cell bridging between filaments due to its large pore size, reducing regenerative speed and capacity. To tackle this issue, a novel biphasic scaffold was developed by a combination of 3D printed poly(ethylene glycol)-terephthalate-poly(butylene-terephthalate) (PEGT/PBT) lattice infilled with a porous silk scaffold (derived from <i>Bombyx mori</i> silk fibroin) to make up a bone phase, which continued to a seamless silk top layer, representing a cartilage phase. Compression testing showed scaffolds had Young's modulus, ultimate compressive strength, and fatigue resistance that would allow for their theoretical survival during implantation and joint articulation without stress-shielding mechanosensitive cells. Fluorescent microscopy showed biphasic scaffolds could support the attachment and spreading of human mesenchymal stem cells from bone marrow (hMSC-BM). These promising results highlight the potential utilization of this novel scaffold for osteochondral tissue regeneration as well as highlighting the potential of infilling silk materials within 3D printed scaffolds to further increase their versatility.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"7606-7618"},"PeriodicalIF":5.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11632666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Payton J Martinez, Jane J Song, Jair I Castillo, John DeSisto, Kang-Ho Song, Adam L Green, Mark Borden
{"title":"Effect of Microbubble Size, Composition, and Multiple Sonication Points on Sterile Inflammatory Response in Focused Ultrasound-Mediated Blood-Brain Barrier Opening.","authors":"Payton J Martinez, Jane J Song, Jair I Castillo, John DeSisto, Kang-Ho Song, Adam L Green, Mark Borden","doi":"10.1021/acsbiomaterials.4c00777","DOIUrl":"10.1021/acsbiomaterials.4c00777","url":null,"abstract":"<p><p>Blood-brain barrier opening (BBBO) using focused ultrasound (FUS) and microbubbles (MBs) has emerged as a promising technique for delivering therapeutics to the brain. However, the influence of various FUS and MB parameters on BBBO and subsequent sterile inflammatory response (SIR) remains unclear. In this study, we investigated the effects of MB size and composition, as well as the number of FUS sonication points, on BBBO and SIR in an immunocompetent mouse model. Using MRI-guided MB + FUS, we targeted the striatum and assessed extravasation of an MRI contrast agent to assess BBBO and RNaseq to assess SIR. Our results revealed distinct effects of these parameters on BBBO and SIR. Specifically, at a matched microbubble volume dose (MVD), MB size did not affect the extent of BBBO, but smaller (1 μm diameter) MBs exhibited a lower classification of SIR than larger (3 or 5 μm diameter) MBs. Lipid-shelled microbubbles exhibited greater BBBO and a more pronounced SIR compared to albumin-shelled microbubbles, likely owing to the latter's poor <i>in vivo</i> stability. As expected, increasing the number of sonication points resulted in greater BBBO and SIR. Furthermore, correlation analysis revealed strong associations between passive cavitation detection measurements of harmonic and inertial MB echoes, BBBO, and the expression of SIR gene sets. Our findings highlight the critical role of MB and FUS parameters in modulating BBBO and subsequent SIR in the brain. These insights inform the development of targeted drug delivery strategies and the mitigation of adverse inflammatory reactions in neurological disorders.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"7451-7465"},"PeriodicalIF":5.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Photocleavable Protein PhoCl-Based Dynamic Hydrogels.","authors":"Jingqi Lei, Hongbin Li","doi":"10.1021/acsbiomaterials.4c01584","DOIUrl":"10.1021/acsbiomaterials.4c01584","url":null,"abstract":"<p><p>Dynamic protein hydrogels have attracted increasing attention owing to their tunable physiochemical and mechanical properties, customized functionality, and biocompatibility. Among the different types of dynamic hydrogels, photoresponsive hydrogels are of particular interest. Here, we report the engineering of a photoresponsive protein hydrogel by using the photocleavable protein PhoCl. We employed the well-developed SpyTag and SpyCatcher chemistry to engineer PhoCl-containing covalently cross-linked hydrogels. In the hydrogel network, PhoCl, which can be cleaved into two fragments upon violet irradiation, is employed as a dynamic structural motif to regulate the cross-linking density of the hydrogel network. The resultant PhoCl-containing hydrogels showed photoresponsive viscoelastic properties. Upon violet irradiation, the PhoCl hydrogels soften, leading to an irreversible reduction in the storage moduli. However, no gel-sol transition was observed. Leveraging this light-induced stiffness change, we employed this hydrogel as a cell culture substrate to investigate the mechanobiological response of NIH-3T3 fibroblast cells. Our results showed that 3T3 cells can change their morphologies in response to the stiffness change of the PhoCl hydrogel substrate dynamically, rendering PhoCl-based hydrogels a useful substrate for other mechanobiological studies.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"7404-7412"},"PeriodicalIF":5.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Magnesium-Based Composite Calcium Phosphate Cement Promotes Osteogenesis and Angiogenesis for Minipig Vertebral Defect Regeneration.","authors":"Fang Tian, Yuqi Zhao, Yuhao Wang, Hailiang Xu, Youjun Liu, Renfeng Liu, Hui Li, Ruojie Ning, Chengwen Wang, Xinlin Gao, Rongjin Luo, Shuaijun Jia, Lei Zhu, Dingjun Hao","doi":"10.1021/acsbiomaterials.4c01521","DOIUrl":"10.1021/acsbiomaterials.4c01521","url":null,"abstract":"<p><p>Calcium phosphate cement (CPC) is an injectable bone cement with excellent biocompatibility, widely used for filling bone defects of various shapes. However, its slow degradation, insufficient mechanical strength, and poor osteoinductivity limit its further clinical applications. In this study, we developed a novel composite magnesium-based calcium phosphate cement by integrating magnesium microspheres into PLGA fibers obtained through wet spinning and incorporating these fibers into CPC. The inclusion of magnesium-based PLGA fibers enhanced the compressive strength and degradation rate of CPC, with the degradation rate of the magnesium microspheres being controllable to allow for the sustained release of magnesium ions. In vitro experiments showed that magnesium-based CPC enhanced the proliferation and migration of MC3T3-E1 and HUVECs. Additionally, the magnesium-based composite CPC not only enhanced osteogenic differentiation of MC3T3-E1 cells but also promoted angiogenesis in HUVECs. In vivo experiments using a vertebral bone defect model in Bama miniature pigs showed that the magnesium-based composite CPC significantly increased new bone formation. Additionally, compared to the CPC group, this composite exhibited significantly higher levels of osteogenic and angiogenic markers, with no inflammation or necrosis observed in the heart, liver, or kidneys, indicating good biocompatibility. These results suggest that magnesium-based composite CPC, with its superior compressive strength, biodegradability, and ability to promote vascularized bone regeneration, holds promise as a minimally invasive injectable material for bone regeneration.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"7577-7593"},"PeriodicalIF":5.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Biomimetic Nanovaccines Restore Immunosuppressive Tumor Antigen-Presenting Cells via the Saposin-Feeding Strategy.","authors":"Bingyuan Fei, Miao Yu, Zheng Wang, Shuo Li","doi":"10.1021/acsbiomaterials.4c01337","DOIUrl":"10.1021/acsbiomaterials.4c01337","url":null,"abstract":"<p><p>Cancer cell membrane-derived biomimetic nanovaccines have shown tremendous potential in cancer immunotherapy. However, their efficacy is restricted by the insufficient cross-presentation of cell membrane-associated antigens. Saposins (SAs), which are vital for membrane vesicle disintegration and cell membrane-associated antigen presentation, are severely deficient in the antigen-presenting cells (APCs) within tumors. Herein, we propose a complementary strategy for increasing the efficacy of biomimetic nanovaccines via the use of SAs. Biomimetic nanovaccines were designed using cancer cell membrane shells to provide a comprehensive array of tumor-associated antigens and reactive oxygen species (ROS)-responsive nanoparticle cores that allowed the codelivery of cytosine-guanine dinucleotides (CpGs) and SAs. The biomimetic nanovaccines were ROS-responsive and highly internalized by APCs, which enabled the release of CpGs and SAs in the endo/lysosomes of APCs. Furthermore, biomimetic nanovaccines increased the activation of immunosuppressive APCs and enhanced T-cell priming by delivering SAs to the APCs. Consequently, biomimetic nanovaccines loaded with SAs not only suppressed tumor growth but also exhibited excellent therapeutic effects in combination with immune checkpoint blockade strategies. Overall, our study provides insights into the development of enhanced biomimetic nanovaccines via integrating SAs and offers a promising strategy for highly effective cancer immunotherapy.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"7482-7491"},"PeriodicalIF":5.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mehmet Serhat Aydin, Nora Marek, Theo Luciani, Samih Mohamed-Ahmed, Bodil Lund, Cecilie Gjerde, Kamal Mustafa, Salwa Suliman, Ahmad Rashad
{"title":"Impact of Porosity and Stiffness of 3D Printed Polycaprolactone Scaffolds on Osteogenic Differentiation of Human Mesenchymal Stromal Cells and Activation of Dendritic Cells.","authors":"Mehmet Serhat Aydin, Nora Marek, Theo Luciani, Samih Mohamed-Ahmed, Bodil Lund, Cecilie Gjerde, Kamal Mustafa, Salwa Suliman, Ahmad Rashad","doi":"10.1021/acsbiomaterials.4c01108","DOIUrl":"10.1021/acsbiomaterials.4c01108","url":null,"abstract":"<p><p>Despite the potential of extrusion-based printing of thermoplastic polymers in bone tissue engineering, the inherent nonporous stiff nature of the printed filaments may elicit immune responses that influence bone regeneration. In this study, bone scaffolds made of polycaprolactone (PCL) filaments with different internal microporosity and stiffness was 3D-printed. It was achieved by combining three fabrication techniques, salt leaching and 3D printing at either low or high temperatures (LT/HT) with or without nonsolvent induced phase separation (NIPS). Printing PCL at HT resulted in stiff scaffolds (modulus of elasticity (E): 403 ± 19 MPa and strain: 6.6 ± 0.1%), while NIPS-based printing at LT produced less stiff and highly flexible scaffolds (E: 53 ± 10 MPa and strain: 435 ± 105%). Moreover, the introduction of porosity by salt leaching in the printed filaments significantly changed the mechanical properties and degradation rate of the scaffolds. Furthermore, this study aimed to show how these variations influence proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells (hBMSC) and the maturation and activation of human monocyte-derived dendritic cells (Mo-DC). The cytocompatibility of the printed scaffolds was confirmed by live-dead imaging, metabolic activity measurement, and the continuous proliferation of hBMSC over 14 days. While all scaffolds facilitated the expression of osteogenic markers (RUNX2 and Collagen I) from hBMSC as detected through immunofluorescence staining, the variation in porosity and stiffness notably influenced the early and late mineralization. Furthermore, the flexible LT scaffolds, with porosity induced by NIPS and salt leaching, stimulated Mo-DC to adopt a pro-inflammatory phenotype marked by a significant increase in the expression of IL1B and TNF genes, alongside decreased expression of anti-inflammatory markers, IL10 and TGF1B. Altogether, the results of the current study demonstrate the importance of tailoring porosity and stiffness of PCL scaffolds to direct their biological performance toward a more immune-mediated bone healing process.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"7539-7554"},"PeriodicalIF":5.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11632652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Enhanced Biodegradation of Silk Fibroin Hydrogel for Preventing Postoperative Adhesion.","authors":"Yusuke Kambe, Yusuke Kawano, Makoto Sasaki, Maito Koga, Nobuyuki Fujita, Tsunenori Kameda","doi":"10.1021/acsbiomaterials.4c01805","DOIUrl":"10.1021/acsbiomaterials.4c01805","url":null,"abstract":"<p><p>An absorbable adhesion barrier is a medical device that prevents postoperative adhesion and matches its biodegradation time with the regeneration period of its target tissues, which is important for antiadhesion effects. Physical hydrogels of <i>Bombyx mori</i> silk fibroin (SF) proteins are degradable <i>in vivo</i>. However, their biodegradation time is too long to exert antiadhesion effects. To shorten the biodegradation time of the SF hydrogels, we decreased the molecular weight (MW) of the SF proteins by alkaline treatment and prepared low-MW (LMW) SF hydrogels. The hydrogels contained less β-sheet crystalline and more amorphous structures than conventional, high-MW (HMW) SF hydrogels. Because of the potential loosened SF molecular structures in the hydrogel networks, the LMW SF hydrogels showed enhanced biodegradation (i.e., shorter <i>in vitro</i> enzymatic biodegradation time and faster <i>in vivo</i> biodegradation rate) as well as a lower affinity for plasma proteins and fibroblasts, which are involved in postoperative adhesion formation. An antiadhesion test using a rat abdominal adhesion model demonstrated that the LMW SF hydrogel applied to the abraded cecum was almost completely degraded within two weeks postimplantation, with a significantly lower adhesion severity score than that in the untreated model rat group. Conversely, the HMW SF hydrogel remained between the cecum and abdominal wall, with the same adhesion severity as that of the untreated model rat group. Therefore, we concluded that the antiadhesion effects of SF hydrogels were induced by enhanced biodegradation. The results of this study indicate the potential of LMW SF hydrogels as absorbable adhesion barriers.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"7441-7450"},"PeriodicalIF":5.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gyuhyung Jin, Haoning Huang, Xiaoping Bao, Sean P Palecek
{"title":"Poly(norepinephrine)-Mediated Universal Surface Modification for Patterning Human Pluripotent Stem Cell Culture and Differentiation.","authors":"Gyuhyung Jin, Haoning Huang, Xiaoping Bao, Sean P Palecek","doi":"10.1021/acsbiomaterials.4c01229","DOIUrl":"10.1021/acsbiomaterials.4c01229","url":null,"abstract":"<p><p>Maintaining undifferentiated states of human pluripotent stem cells (hPSCs) is key to accomplishing successful hPSC research. Specific culture conditions, including hPSC-compatible substrates, are required for the hPSC culture. Over the past two decades, substrates supporting hPSC self-renewal have evolved from undefined and xenogeneic protein components to chemically defined and xenogeneic-free materials. However, these synthetic substrates are often costly and complex to use, leading many laboratories to continue using simpler undefined extracellular matrix (ECM) protein mixtures. In this study, we present a method using poly(norepinephrine) (pNE) for surface modification to enhance the immobilization of ECM proteins on various substrates, including polydimethylsiloxane (PDMS) and ultralow attachment (ULA) hydrogels, thereby supporting hPSC culture and maintenance of pluripotency. The pNE-mediated surface modification enables spatial patterning of ECM proteins on nonadhesive ULA surfaces, facilitating tunable macroscopic cell patterning. This approach improves hPSC attachment and growth and allows for cell patterning to study the effects of anisotropic environments on the hPSC fate. Our findings demonstrate the versatility and simplicity of pNE-mediated surface modification for improving hPSC culture and spatially controlled differentiation into endothelial cells and cardiomyocytes on previously nonamenable substrates, providing a valuable tool for tissue engineering and regenerative medicine applications.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":"7429-7440"},"PeriodicalIF":5.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhao Guo, Xing Liu, Yan Xia, Jie Wang, Jiaqi Li, Liping Wang, Yimiao Li, Shuang Jia, Yinan Sun, Jian Feng, Jingxia Huang, Yuxin Dong, Liyao Wang, Xinyu Li
{"title":"Assembly of Recombinant Proteins into β-Sheet Fibrillating Peptide-Driven Supramolecular Hydrogels for Enhanced Diabetic Wound Healing.","authors":"Zhao Guo, Xing Liu, Yan Xia, Jie Wang, Jiaqi Li, Liping Wang, Yimiao Li, Shuang Jia, Yinan Sun, Jian Feng, Jingxia Huang, Yuxin Dong, Liyao Wang, Xinyu Li","doi":"10.1021/acsbiomaterials.4c01723","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c01723","url":null,"abstract":"<p><p>Supramolecular hydrogels offer a noncovalent binding platform that preserves the bioactivity of structural molecules while enhancing their stability, particularly in the context of diabetic wound repair. In this study, we developed protein-peptide-based supramolecular hydrogels by assembling β-sheet fibrillizing peptides (designated Q11) with β-tail fused recombinant proteins. The Q11 peptides have the ability to drive the gradated assembly of N- or C-terminal β-sheet structure (β-tail) fused recombinant proteins. We first investigated the assembly properties of Q11 and assessed its stability under varying pH and temperature conditions by combining Q11 with two β-tail fused fluorescent proteins. The results showed that Q11 enhanced the tolerance of the fluorescent proteins to changes in pH and temperature. Building upon these findings, we designed collagen-like proteins and Sonic Hedgehog-fused recombinant proteins (CLP-Shh) that could be assembled with Q11 to form peptide-protein supramolecular hydrogels. These hydrogels demonstrated the ability to improve cell viability and migration and upregulate key markers of cell growth. Further in vivo studies revealed that the Q11-driven supramolecular hydrogel effectively enhances diabetic wound healing and epidermal regeneration by promoting the expression of epidermal-related proteins and immune factors. This study highlights the potential of supramolecular hydrogels for clinical applications and their promise in the development of biofunctional hydrogels for therapeutic use.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}