Engineered regenerationPub Date : 2026-01-01Epub Date: 2026-07-15DOI: 10.1016/j.engreg.2026.07.002
Sriram Bharath Gugulothu, Kaushik Chatterjee
{"title":"Dynamic 4D-bioprinted duct-like microenvironments for triple-negative breast cancer modeling and drug response","authors":"Sriram Bharath Gugulothu, Kaushik Chatterjee","doi":"10.1016/j.engreg.2026.07.002","DOIUrl":"10.1016/j.engreg.2026.07.002","url":null,"abstract":"<div><div>Four-dimensional (4D) bioprinting offers a facile strategy for generating dynamic tissue constructs with physiologically relevant geometries for disease modeling. Here, we extend a previously established visible-light-crosslinkable hydrogel system to fabricate self-folding, duct-mimetic tubular constructs for triple-negative breast cancer (TNBC) modeling under dynamic culture conditions. Systematic optimization of photoinitiator concentration in bioink, scaffold thickness and length, cell density, and solvent conditions identified parameters that enabled robust self-folding of TNBC cell-laden constructs into closed thin-walled (≤ 0.8 mm) tubes with an internal diameter of ≈2.1 mm, comparable to those of mammary ducts. Nanoindentation confirmed a stable mechanical gradient in the tubular scaffolds over 14 days, with a softer outer surface (≈0.5 kPa) and a stiffer inner surface (≈20 kPa). Under rocker-based dynamic culture, MDA-MB-231-laden tubular constructs showed improved viability and a 1.4-fold increase in metabolic activity compared with their static culture counterparts at Day 14. Dynamic culture also promoted the appearance of mesenchymal-like spindle morphology by Day 7 and cellular aggregation by Day 14. Following doxorubicin treatment at Day 14, dynamically cultured tubes exhibited enhanced chemoresistance compared to static constructs, with lower cell death (65%vs. 75%) at approximately 10-fold higher half-maximal inhibitory concentration (IC<sub>50</sub>) (10 µM). Together, these findings establish a 4D-bioprinted TNBC model with a duct-like architecture and mechanical anisotropy to investigate the role of passive (stiffness gradients) and dynamic (interstitial flow) biophysical cues on tumor cell behavior and therapeutic response.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"7 ","pages":"Pages 121-134"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148634756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Engineered regenerationPub Date : 2026-01-01Epub Date: 2026-05-29DOI: 10.1016/j.engreg.2026.05.002
Xiaoman Wu , Jia Gao , Fan Ding , Di Suo , Guoqing Pan
{"title":"Rational molecular design to elicit biological functions for modulating cellular and tissue responses","authors":"Xiaoman Wu , Jia Gao , Fan Ding , Di Suo , Guoqing Pan","doi":"10.1016/j.engreg.2026.05.002","DOIUrl":"10.1016/j.engreg.2026.05.002","url":null,"abstract":"<div><div>The regulation of cellular signaling relies fundamentally on molecular recognition. However, the direct application of natural biomolecules is often limited by poor stability, insufficient specificity, and inadequate controllability. Rational molecular design has therefore emerged as an effective approach to bridge chemical structure and biological function, enabling the development of engineered systems with programmable recognition and tunable bioactivity. This review provides a function-oriented perspective on molecular imprinting, affinity screening, dynamic combinatorial chemistry, and biomolecular modification. These approaches enable the construction of synthetic or semi-synthetic macromolecules with tailored affinity, multivalency, and environmental responsiveness. Such engineered systems generate diverse biofunctional outputs, including signal interception, receptor clustering, and adaptive regulation, thereby enabling precise modulation of cellular signaling pathways. Furthermore, this review highlights the recent advances in applying these design principles to biomedical scenarios, including intelligent drug delivery, immunotherapy, and tissue engineering. Finally, the current technological challenges are summarized in vivo stability, insufficient spatiotemporal control, and barriers to clinical translation. Future efforts will likely focus on the development of adaptive and integrative molecular systems with enhanced precision and controllability, enabling the rational programming of biological functions and accelerating their clinical translation.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"7 ","pages":"Pages 71-93"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148241837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Engineered regenerationPub Date : 2026-01-01Epub Date: 2026-09-09DOI: 10.1016/j.engreg.2026.08.005
S-Sina Mohammadi, Sunjeev S. Phull, Ryan J. Gilbert, Mark R. Towler
{"title":"Injectable borate/borosilicate bioactive glass systems for the regeneration of hard tissue – A critical review of the literature","authors":"S-Sina Mohammadi, Sunjeev S. Phull, Ryan J. Gilbert, Mark R. Towler","doi":"10.1016/j.engreg.2026.08.005","DOIUrl":"10.1016/j.engreg.2026.08.005","url":null,"abstract":"<div><div>Bone defects caused by trauma, infection, or tumor resection remain difficult to treat because successful repair requires both structural restoration and control of the local pathological microenvironment. Osteolysis, defined as pathological bone resorption, is central to many of these conditions and is commonly driven by excessive osteoclast activity. Clinically translated injectable products such as NovaBone® Putty demonstrate the value of moldable bioactiveglass grafts for defect filling; however, conventional silicate bioactive glasses are permanent and provide limited therapeutic ion release. This limitation has motivated the development of injectable borate bioactive glass (B-BGs) and injectable borosilicate bioactive glass (BS-BG) systems as more degradable, ion-releasing platforms for hard-tissue regeneration. Early borate/chitosan cements showed injectability, apatite formation, and bone-regenerative potential, but rapid boron release raised concerns regarding biological safety. SrO incorporations was therefore introduced to moderate dissolution while enhancing osteogenesis. Because vascularization is also essential for defect repair, subsequent systems targeted vascular endothelial growth factor (VEGF) signaling either through direct VEGF delivery or indirect Cu-mediated VEGF upregulation. For osteomyelitis, where bacterial infection accelerates bone destruction, B-BG/BS-BG cements have been loaded with vancomycin or gentamicin to provide localized antibiotic release after debridement. Magnetothermal systems further expand this approach by incorporating magnetic nanoparticles that generate heat under an alternating magnetic field to disrupt bacteria or ablate tumor cells. In osteosarcoma, B-BG/BS-BG platforms offer combined bone regeneration and local therapy through magnetic hyperthermia, metal-containing adhesives, and dual hyperthermia/chemotherapy systems incorporating doxorubicin. Overall, these systems show promise but require stricter release control, safety validation, and mechanical durability assessment.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"7 ","pages":"Pages 259-275"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148934957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Engineered regenerationPub Date : 2026-01-01Epub Date: 2026-07-29DOI: 10.1016/j.engreg.2026.07.005
Qianrong Yang, Zhicheng Shi, Guoping Zhao, Hui Wang
{"title":"On-chip hydrogel microfibers for biomedical sensing applications","authors":"Qianrong Yang, Zhicheng Shi, Guoping Zhao, Hui Wang","doi":"10.1016/j.engreg.2026.07.005","DOIUrl":"10.1016/j.engreg.2026.07.005","url":null,"abstract":"<div><div>Hydrogel microfibers resemble native biological filaments due to their hierarchical structure, tunable physicochemical properties, and biocompatibility, thus holding transformative potential in biomedical sensing. Conventional fabrication methods are limited in topological precision, spatiotemporal functionalization, and controllability. Recent microfluidic technology is advancing programmable microfiber engineering through functional units, including hydrodynamic focusing, laminar flow control, and in situ polymerization modules. In this review, we introduce common hydrogel materials used in microfiber fabrication and summarize microfluidic chip design strategies that enable spatial control and assembly. Furthermore, we comprehensively highlight the recent progress in hydrogel microfibers for biomedical sensing applications, and discuss how to advance hydrogel microfiber-based intelligent sensing ecosystems through multidisciplinary integration.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"7 ","pages":"Pages 188-203"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148843648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Reframing hair follicle development through Tissue Engineering Triad for hair organoid construction","authors":"Khaow Tonsomboon, Thanchanok Khorporn, Patsawee Sriboonaied, Phasin Srinualchai, Sarochapat Sutikulsombat, Peerapat Thongnuek","doi":"10.1016/j.engreg.2026.07.003","DOIUrl":"10.1016/j.engreg.2026.07.003","url":null,"abstract":"<div><div>Hair follicles are dynamic mini-organs that cyclically regenerate through coordinated epithelial–mesenchymal interactions and precisely regulated molecular signalling. Reconstructing this complexity <em>in vitro</em> remains a central challenge in regenerative dermatology. This review reframes hair-follicle morphogenesis through the Tissue Engineering Triad (TET), which consists of cells, signals, and materials, to provide a design-oriented perspective for organoid construction. Each hair-cycle phase (anagen, catagen, telogen) is analysed in terms of its cellular composition, signalling environment, and extracellular matrix (ECM) dynamics, emphasizing how these triadic components govern homeostasis and regeneration. The telogen-to-anagen transition is highlighted as a natural model of reactivation, linking cellular reprogramming, morphogen signalling, and matrix remodelling. Building on these biological insights, recent advances in hair-follicle organoid engineering are reviewed, covering cell sources, morphogen combinations, ECM scaffolds, and the developmental fidelity of resulting structures. Finally, the challenges of maintaining dermal papilla inductivity, achieving vascularization, and ensuring translational scalability are discussed. Framing hair development through the TET paradigm offers a unifying roadmap for transforming developmental principles into practical strategies for hair regeneration.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"7 ","pages":"Pages 135-155"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148634676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Engineered regenerationPub Date : 2026-01-01Epub Date: 2026-05-02DOI: 10.1016/j.engreg.2026.05.001
Lucas Pereira Lopes de Souza , Joao Henrique Lopes , Luis Felipe Moreira Oliveira , Farah Naz Safdar Raja , Archana Singh , Shirin Hanaei , Darrell Green , Adrian Gardner , Jonathan Stevenson , Richard Alan Martin
{"title":"Multi-modal therapeutic action of gallium-containing bioactive glass against osteosarcoma and bacterial pathogens","authors":"Lucas Pereira Lopes de Souza , Joao Henrique Lopes , Luis Felipe Moreira Oliveira , Farah Naz Safdar Raja , Archana Singh , Shirin Hanaei , Darrell Green , Adrian Gardner , Jonathan Stevenson , Richard Alan Martin","doi":"10.1016/j.engreg.2026.05.001","DOIUrl":"10.1016/j.engreg.2026.05.001","url":null,"abstract":"<div><div>Despite multimodal therapy, bone tumours can lead to high morbidity and poor survival, with recurrent limited success from trials investigating targeted or immunotherapies. Surgery remains essential and is often the only option available for refractory disease, skeletal metastases, and some benign bone lesions. However, primary bone tumours, such as osteosarcoma, often recur locally when complete resection is hindered by limited safety margins or proximity to vital structures. A multifunctional biomaterial capable of eradicating residual tumour cells while promoting bone regeneration could significantly improve outcomes of surgical procedures in these clinical settings. Here, we report the anticancer and antibacterial properties of gallium-containing bioactive glasses (Ga-BGs). We show that osteosarcoma cell lines are especially sensitive to gallium and that Ga-BGs can release therapeutic levels of gallium ions that selectively kill osteosarcoma cells. Our mechanistic investigation reveals that gallium promotes a multi-pronged molecular attack on key hallmarks of cancer cells, primarily through disrupting iron metabolism leading to increased oxidative stress, induction of cell death pathways, and suppression of oncogenic and metastatic signalling. Moreover, gallium nitrate and Ga-BGs are shown to present inhibitory effects upon gram-negative bacteria <em>P. aeruginosa</em>. Taken together, our results indicate that Ga-BGs constitute a model biomaterial for the development of multi-functional scaffolds for the treatment of osteosarcoma.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"7 ","pages":"Pages 58-70"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148183754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Engineered regenerationPub Date : 2026-01-01Epub Date: 2026-09-03DOI: 10.1016/j.engreg.2026.08.003
Jie Xu, Yecheng Lu, Xuan Wu, Fansen Xu, Jingyang Shan, Yubao Wang
{"title":"Polydopamine nanoparticles integrated microneedle patch for near-infrared-II light triggered thrombolysis","authors":"Jie Xu, Yecheng Lu, Xuan Wu, Fansen Xu, Jingyang Shan, Yubao Wang","doi":"10.1016/j.engreg.2026.08.003","DOIUrl":"10.1016/j.engreg.2026.08.003","url":null,"abstract":"<div><div>Traditional thrombolytic drugs such as urokinase and tissue plasminogen activator for vascular blockage remain large challenging due to their off-target side effects, low bioavailability and limited penetration abilities in blood clots, leading to the limited therapeutic effect. Considering the rapid developments of nanotechnology, the exploration of an innovative nanomaterials-based thrombolytic strategy for treating venous thromboembolism is highly demanded. Here, we present a polydopamine nanoparticles integrated microneedle patch for near-infrared-II light triggered thrombolysis in vitro and in vivo. Polydopamine nanoparticles with the near-infrared-II photothermal conversion performance were prepared at room temperature in the dark, and then were integrated into microneedle patch using the common polydimethylsiloxane microneedle mold. Polydopamine nanoparticles integrated microneedle patch not only showed good mechanical performance to easily insert into the skin without breaking, but also showed outstanding near-infrared-II photothermal conversion abilities. In vitro thrombolytic results proved that polydopamine nanoparticles integrated microneedle patch could induce the blood clot lysis in vitro under 1064 nm light irradiation for 5 min. Also, this microneedle patch showed effective thrombolysis effect by near-infrared-II light induced local overheating against the femoral vein thrombi model of female BALB/c mice. Overall, this microneedle patch has the great potential to treat venous thromboembolism.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"7 ","pages":"Pages 222-227"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148934960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Engineered regenerationPub Date : 2026-01-01Epub Date: 2026-01-16DOI: 10.1016/j.engreg.2026.01.001
Kenichi Arai , Kazuya Fukuhara-Obonai , Soichi Ishimaru , Nobuhiko Kojima , Tanveer Ahmad Mir , Takahiro Kitsuka , Masahiro Hosaka
{"title":"Development of a primary hepatocyte-based preclinical spheroid model system for the analysis of Phase I and Phase II enzyme activity in vitro","authors":"Kenichi Arai , Kazuya Fukuhara-Obonai , Soichi Ishimaru , Nobuhiko Kojima , Tanveer Ahmad Mir , Takahiro Kitsuka , Masahiro Hosaka","doi":"10.1016/j.engreg.2026.01.001","DOIUrl":"10.1016/j.engreg.2026.01.001","url":null,"abstract":"<div><div>Hepatic spheroids formed by the spontaneous self-aggregation of hepatocytes maintain better liver function than two-dimensional (2D) monolayer cultures. Although structural polarity and intercellular adhesion can be maintained in hepatic spheroids, cell-extracellular matrix (ECM) interactions cannot be reproduced in spheroid-based models. In this study, we leveraged customizable ECM component and fabricated hepatic by injecting a cell suspension supplemented with primary mouse hepatocytes and Matrigel into a high-density methylcellulose (MC) solution. Amongst other findings, gene expression analysis of hepatic spheroid aggregates containing Matrigel revealed elevated levels of drug-metabolizing enzymes (Phase I and II) and transporters (compared to spheroids without Matrigel). Furthermore, the induction of drug metabolism enzymes and activity in hepatic spheroids containing Matrigel also increased compared to those without Matrigel. Lastly, we demonstrated that hepatic spheroids containing Matrigel can maintain liver function by increasing HNF4α through activation of Hippo signaling. Overall, our results indicate that high-performance hepatic spheroids containing Matrigel can maintain liver function through cell-cell and cell-ECM interactions and can be used to increase the efficiency of drug screening.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"7 ","pages":"Pages 1-11"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146057383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Engineered regenerationPub Date : 2026-01-01Epub Date: 2026-01-17DOI: 10.1016/j.engreg.2025.11.004
Hong Zhang , Yujian Xu , Yangwu Chen , Kun Zhao , Tianshun Fang , Youguo Liao , Xiangming Ye , Xiao Chen , Zi Yin
{"title":"Harnessing the interplay between tendon stem/progenitor cell and microenvironment boosts tendon tissue regeneration","authors":"Hong Zhang , Yujian Xu , Yangwu Chen , Kun Zhao , Tianshun Fang , Youguo Liao , Xiangming Ye , Xiao Chen , Zi Yin","doi":"10.1016/j.engreg.2025.11.004","DOIUrl":"10.1016/j.engreg.2025.11.004","url":null,"abstract":"<div><div>Tendon injuries are common musculoskeletal disorders characterized by limited natural healing capacity and inability to restore the original structure and function of tendons. Tendon tissue engineering based on tendon stem/progenitor cells (TSPCs) offers a potential strategy for tendon injury treatments. The function regulation of TSPCs is influenced by both <em>in vivo</em> and <em>in vitro</em> microenvironmental factors. Here, we provide a concise summary of the various subpopulations of TSPCs identified thus far. Additionally, we explore the current research progress on the <em>in vivo</em> microenvironment of TSPCs. Notably, we first introduce the concept of a \"degeneration loop,\" which highlights the intricate interplay between the tendon microenvironment and TSPCs. Developing from this concept, we derive the theory and strategic framework of \"Remodel niche - Disrupt Degeneration Loop - Tendon Healing\" for effective tendon regeneration. Furthermore, we present an overview of the latest advances in the regulation of TSPCs expansion and differentiation through manipulation of the microenvironment <em>in vitro</em> and <em>in vivo</em>. Lastly, we address the challenges and related prospects encountered in the regenerative application of TSPCs subpopulations. A deeper multi-scale understanding of the interplay between distinct TSPCs subpopulations and their microenvironment will greatly contribute to the development of innovative tissue engineering strategies for successful tendon regeneration.</div></div>","PeriodicalId":72919,"journal":{"name":"Engineered regeneration","volume":"7 ","pages":"Pages 12-29"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146081929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}