BIOMATERIALS
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2026
·
IF 13.6
Xianghang Chen,Beini Wang,Jiayan Hui,Wei Shen,Longyang Xu,Anwen Lai,Rong Huang,Fuyi Yan,Qimin Yao,Zheng Zhang,Jie Xu,Xiong Cai,Fenzan Wu,Siwang Hu,Jian Xiao,Zhenglin Li
Spinal cord injury (SCI) causes pathological extracellular matrix (ECM) deposition and tissue stiffening, impeding axonal regeneration and disrupting homeostasis. Galardin-mediated inhibition of matrix metalloproteinases reduces ECM deposition and promotes recovery, but systemic administration fails to adequately address local microenvironment deterioration. We therefore explore a localized biomaterial delivery strategy via regulating the crosslinking degree of hydrogel matrix, in which high-crosslinking density of hydrogel (HCGH) tends to exacerbate neuroinflammation via Piezo1 activation as well as Wwtr1-dependent macrophage reprogramming. Based on this, we fabricate an integrated therapeutic platform where pH-responsive curcumin-succinate self-assembled prodrug nanoparticles (co-loaded with Galardin and basic fibroblast growth factor, denoted as CrS-GF NPs) are encapsulated in a low-crosslinking hydrogel (LCGH). By thorough testing on the compression spinal cord injury model of mice, the LCGH@CrS-GF system not only modulates excessive ECM deposition and neuroinflammation, but also provides sufficient neurotrophic support, thereby facilitating smooth axonal regeneration and functional restoration of the damaged spinal cords in a collaborative manner. Our study highlights the importance of using hydrogels with tailored crosslinking density to deliver therapeutics for SCI repair by stimulating beneficial biological responses and manipulating ECM deposition.
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高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Xiao-Ting Xie,Cheng-Hao Gao,Lin-Fang Tan,Liang-Xi Chen,Jin-Xuan Fan,Wei Xiong,Kai Cheng,Yuan-Di Zhao,Bo Liu
The treatment of infected diabetic wounds remains a significant clinical challenge due to pathogen infection, excessive inflammation, and impaired angiogenesis with troubled extracellular matrix (ECM) - cell and cell - cell interaction. Herein, we prepared a Janus polypeptide-engineered hydrogel with programmable function driven by self-assembly of the same A domain. The hydrogel was composed of a V8-degradable AC 10 A layer loaded with hybrid phages (ABC) for precise bacterial inhibition and a PC 10 ARGD layer loaded with Mn-based mineralized erythrocyte (PEM) for continuous supply oxygen on demand. The results of laser speckle contrast imaging, photoacoustic imaging, and hyperspectral imaging demonstrated that the AC 10 A@BP-Ce6/PC 10 AR@EM hydrogel (ABC/PEM) accelerated the reconstruction of normal skin structure by breaking the oxygen diffusion barrier and supplying oxygen on demand to promote angiogenesis and functionalization. In addition, in vitro and in vivo experiment results showed that the ABC/PEM hydrogel can mimic positive ECM - cell interaction to inhibit the polarization of macrophage towards M1-type to slow down the inflammatory process by down-regulated yes-associated protein (YAP), and relieve the mechanical tension of fibroblasts and keratinocytes. Finally, the ABC/PEM hydrogel promotes a healing rate of 98.83 % on day 21 and results in the number of dermal appendages being eight times that of the negative group. This work presents an effective strategy for diabetes-related chronic infected wound management.
研究领域:
生物医学工程
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组织工程
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伤口愈合
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糖尿病研究
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材料科学
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PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Yujie Zhang,Yuan Zhao,Chuanfeng An,Yiyang Guo,Yubin Ma,Fei Shao,Yonggang Zhang,Kai Sun,Fang Cheng,Changle Ren,Lijun Zhang,Bingbing Sun,Yang Zhang,Huanan Wang
Recent progress in stem cell therapy has demonstrated the therapeutic potential of intravenous stem cell infusions for treating the life-threatening lung disease of pulmonary fibrosis (PF). However, it is confronted with limitations, such as a lack of control over cellular function and rapid clearance by the host after implantation. In this study, we developed an innovative PF therapy through tracheal administration of microfluidic-templated stem cell-laden microcapsules, which effectively reversed the progression of inflammation and fibrotic injury. Our findings highlight that hydrogel microencapsulation can enhance the persistence of donor mesenchymal stem cells (MSCs) in the host while driving MSCs to substantially augment their therapeutic functions, including immunoregulation and matrix metalloproteinase (MMP)-mediated extracellular matrix (ECM) remodeling. We revealed that microencapsulation activates the MAPK signaling pathway in MSCs to increase MMP expression, thereby degrading overexpressed collagen accumulated in fibrotic lungs. Our research demonstrates the potential of hydrogel microcapsules to enhance the therapeutic efficacy of MSCs through cell-material interactions, presenting a promising yet straightforward strategy for designing advanced stem cell therapies for fibrotic diseases.
研究领域:
干细胞疗法
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肺医学
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生物材料
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免疫学
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组织工程
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PubMed
高影响因子
EUROPEAN POLYMER JOURNAL
·
2026
·
IF 6.8
Xinyu Du,Yiran Li,Sheng Zhang,Gangqiang Zhang
Design and construction of novel bone scaffolds integrating great structural adaptability and enhanced biological activities are urgently required in clinics. Herein, a composite scaffold made from piezoelectric poly (L-lactic acid) (PLLA) microfibers and chitosan (CS)/polyethylene oxide (PEO) nanofibers was fabricated by using a co-electrospinning strategy. Moreover, the bioadditive, nano-hydroxyapatite (nHAP), was loaded into the PLLA nanofibers during co-electrospinning to generate nHAP/PLLA + CS/PEO micro-nano fiber scaffolds. The scaffold showed a bimodal fiber diameter distribution (282.5 ± 11.4 nm, 1910.5 ± 22.2 nm) and a pore size of ∼ 3.3 μm, mimicking the extracellular matrix (ECM) structure to support osteoblast proliferation. Compared with traditional PLLA scaffold, the composite scaffold exhibited better performance. The surface contact angle had decreased from 136.7° ± 3.5° to 72.9° ± 2.1°. The mechanical properties had increased from 3.2 ± 0.2 MPa to 5.5 ± 0.6 MPa. Furthermore, the addition of nHAP enhanced the piezoelectric properties of the fiber scaffold. Under a load of 2 N, its piezoelectric voltage could approximately reach 250 mV. The antibacterial test results demonstrated that nHAP/PLLA + CS/PEO achieved approximately 99% inhibition against Staphylococcus aureus ( S. aureus ) and Escherichia coli ( E. coli ), potentially reducing post-implantation infection rates. Cell experiments further demonstrated that micro-nano fibrous composite scaffolds not only promoted the proliferation of osteoblasts but also enhanced the expression of key osteogenic proteins such as type I collagen (COL I), osteopontin (OPN), and osteocalcin (OCN). Overall, the nHAP/PLLA + CS/PEO fiber scaffolds held considerable promise for accelerating bone repair.
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高影响因子
Materials Today Bio
·
2024
·
IF 8.7
Changxing Liu,Yawei Sun,Dengju Li,Fan Wang,Haojue Wang,Senbo An,Shui Sun
Osteoarthritis (OA) is characterized by progressive and irreversible damage to the articular cartilage and a consecutive inflammatory response. However, the majority of clinical drugs for OA treatment only alleviate symptoms without addressing the fundamental pathology. To mitigate this issue, we developed an inflammation-responsive carrier and encapsulated bioactive material, namely, LDH@TAGel. The LDH@TAGel was designed with anti-inflammatory and antioxidative abilities, aiming to directly address the pathology of cartilage damage. In particular, LDH was confirmed to restore the ECM secretion function of damaged chondrocytes and attenuate the expression of catabolic matrix metalloproteinases (Mmps). While TAGel showed antioxidant properties by scavenging ROS directly. In vitro evaluation revealed that the LDH@TAGel could protect chondrocytes from inflammation-induced oxidative stress and apoptosis via the Nrf2/Keap1 system and Pi3k-Akt pathway. In vivo experiments demonstrated that the LDH@TAGel could alleviated the degeneration and degradation of cartilage induced by anterior cruciate ligament transection (ACLT). The OARSI scores indicating OA severity decreased significantly after three weeks of intervention. Moreover, the IVIS image revealed that LDH@TAGel enhances the controlled release of LDH in a manner that can be customized according to the severity of OA, allowing adaptive, precise treatment. In summary, this novel design effectively alleviates the underlying pathological causes of OA-related cartilage damage and has emerged as a promising biomaterial for adaptive, cause-targeted OA therapies.
研究领域:
生物材料
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组织工程
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骨科
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药学
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生物医学工程
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PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2026
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IF 12.5
Jiayi Zhang,Chi Ma,Haifeng Zhang,Haibing Wang,Siya Wang,Xueting Ren,Licheng Zhang,Menghuan Li,Zhong Luo,Xiang Cui
Mitochondrial dysfunction of nucleus pulposus cells (NPCs) drives IDD. • An injectable liposome-anchored ECM-mimetic hydrogel (ILH) is developed. • ILH repairs NPC mitochondria via SIRT1-AMPK-PGC-1α activation and ROS scavenging. • ILH reverses NPC senescence to restore disc structure and function. Mitochondrial dysfunction is a key driver of nucleus pulposus cell (NPC) senescence with crucial roles in orchestrating intervertebral disc (IVD) degeneration. However, the development of effective therapies is limited by the complex IVD structure and mitochondrial pathology. Here, an injectable liposome-anchored extracellular matrix (ECM)-mimetic hydrogel (ILH) was engineered for treating IVD degeneration via restoring mitochondrial biogenesis in senescent NPCs. Specifically, nicotinamide mononucleotide (NMN)-loaded liposomes were functionalized with the mitochondria-targeting peptide SS31 (MTLs) and incorporated together with Vitamin K 2 (VK 2 ) into an injectable hyaluronic acid-gelatin hydrogel crosslinked via dynamic Schiff base and boronate ester bonds. ILHs provide immediate mechanical support to degenerative IVDs while enabling on-demand release of encapsulated MTLs and VK 2 within the nucleus pulposus (NP). MTLs facilitates mitochondrial targeted-NMN delivery to replenish intracellular NAD + levels and activate SIRT1 signaling in senescent NPCs, thereby promoting AMPK-dependent mitochondrial biogenesis and suppressing the p53-associated senescence programs. On the other hand, SS31 alleviates cardiolipin peroxidation and preserves mitochondrial cristae integrity, while VK 2 activates the antioxidative Nrf2/HO-1 pathway to further improve mitochondrial quality control. Collectively, these coordinated effects enable comprehensive mitochondrial repair while further maintaining their structural and functional integrity in senescent NPCs, providing a promising therapeutic strategy for clinical treatment of IVD degeneration.
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·
IF 15
Wang Yifan,Zou Minglang,Cheng Junyao,Chen Cuiping,Zhang Chuyue,Yan Taoxu,Wang Xianzheng,Tian Zheng,Zhang Zhenyue,Mao Kaige,Li Bo,Liu Xuanhui,Liu Haoming,Chi Pengfei,Pan Zhimin,Weng Zuquan,Huang Da,Liu Jianheng,Wang Zheng
Intervertebral disc degeneration, the leading cause of chronic low back pain, remains incurable with traditional conservative therapies limited to symptomatic alleviation. We present an ECM-mimetic injectable hydrogel (HPTC) synthesized via dynamic crosslinking of hyaluronic acid-phenylboronic acid (HA-PBA) and tannic acid-cerium(III) metal-polyphenol networks (TA-Ce³⁺ MPNs), which faithfully recapitulates native nucleus pulposus ECM to enable functional tissue regeneration. In vitro, HPTC presented broad-spectrum reactive oxygen species scavenging and downregulated pro-inflammatory cytokine expression (TNF-α, IL-1β, IL-6), while upregulating anti-inflammatory markers (IL-4, IL-10). Crucially, Ce³⁺ effectively reduced dissolved oxygen levels (to 105% vs. 115% in control at 15 min), thereby promoting HIF-1α signal expression and mitigating nucleus pulposus cells senescence under H₂O₂-induced oxidative stress. In rat and rabbit intervertebral disc degeneration models, a single, minimally invasive injection of the ECM-mimetic HPTC hydrogel preserved the disc height index and magnetic resonance imaging signal intensity, enhanced aggrecan and collagen II deposition, suppressed inflammatory mediators, and elevated HIF-1α while reducing p21 expression in situ. Transcriptomic analysis further implicated HIF-1α pathways in ECM regeneration. All these findings demonstrate that the HPTC hydrogel leverages metal-polyphenol chemistry within an ECM-inspired framework to synergistically modulate oxygen homeostasis, oxidative stress, and inflammation, offering a bifunctional and biomimetic platform for disc regeneration. Graphical
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高影响因子
Advanced Science
·
2026
·
IF 14.1
Junzhe Fu,Fan Jia,Yixian Mu,Wanzhe Liu,Dingqi Tang,Qiao Jin,Jian Ji,Youxiang Wang
Hypertrophic scars (HS) are sustained by a self‐perpetuating extracellular matrix (ECM)–fibroblast feedback loop, in which activated fibroblasts drive excessive ECM deposition, while the resulting matrix stiffening in turn reinforces fibroblast activation. Although advanced fibroblast‐suppression strategies are being actively developed, this matrix‐driven profibrotic feedback remains poorly integrated into HS therapeutic strategies and insufficiently targeted. Here, we introduce an enzyme–nitric oxide (NO) co‐regulatory system for HS: enzymatic degradation of pre‐existing ECM relieves aberrant mechanical cues, while NO‐mediated modulation of fibroblast phenotypes restrains excessive collagen synthesis, thereby inducing mutually reinforcing remodeling across the ECM–fibroblast axis. Specifically, a microneedle platform is developed for localized co‐delivery of the thermosensitive protease bromelain (Bro) and NO‐donor‐functionalized polydopamine nanoparticles (PDA‐NO). Upon near‐infrared irradiation, precise photothermal stimulation further enhances Bro activity and accelerates NO release, enabling controlled amplification of the co‐regulatory effect. In vivo studies demonstrate that this system alleviates HS and restores balanced fibrotic remodeling, as evidenced by coordinated suppression of YAP signaling and the TGF‐β1/α‐SMA/Collagen I axis, supporting effective interruption of the fibrotic feedback loop. Distinct from existing fibroblast‐centric approaches, this study establishes pathological ECM–fibroblast crosstalk as a key mechanistic entry point for HS, advancing a mechanism‐driven, materials‐enabled framework for antifibrotic strategy design. An enzyme–nitric oxide (NO) co‐regulatory strategy reprograms pathological extracellular matrix (ECM)–fibroblast crosstalk in hypertrophic scars. Enzymatic degradation of pre‐existing ECM relieves aberrant mechanical cues, while NO‐mediated fibroblast phenotypic modulation restrains excessive collagen synthesis. Supported by photothermal amplification and localized microneedle delivery, this strategy interrupts the fibrotic feedback loop and restores balanced remodeling to alleviate hypertrophic scarring.
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高影响因子
Biomaterials Advances
·
2026
·
IF 6.7
Yutian Huang,Pei Peng,Tongtong Huang,Yulu Ying,Cao Yao,Siying Cai,Pujie An,Linhan Ye,Wei Li,Yang Xiong,Mancang Gu,Chaofeng Mu,Guilin Cheng
A three-dimensional vascular niche model is engineered in decellularized bone marrow ECM-based hydrogel with tunable mechanics. • Endothelial cells provide the primary adhesive interface for hematopoietic cells in mimic bone marrow vascular niche. • Mesenchymal stromal cells mainly dominate vascular niche regulation of both HSC stemness and leukemic chemoresistance. Bone marrow vascular niche regulates both hematopoiesis and hematopoietic disorders, including acute and chronic leukemia. However, it is still not fully understood at the structural and functional levels owing to its inaccessibility in situ . Here, a biomimetic bovine decellularized bone marrow extracellular matrix (dbECM) mixed hydrogel was developed. Proteomics validation confirmed its retention of bone marrow-specific ECM components. The mechanical properties and microstructure of the mixed hydrogel provided a biomimetic platform that integrates biochemical and physical cues for niche functional studies. Vascular networks with multilayered murine C166 endothelial cells (ECs) and mesenchymal stromal cells (MSCs: C3H10T1/2 cells or primary murine bone marrow-derived MSCs) were successfully formed in the mixed hydrogel scaffold. This murine vascular niche model can be utilized to unravel the dynamic events of Lin − c-Kit + hematopoietic cells /leukemic cell interaction with niche components. MSCs mainly contributed to hematopoietic stem cell preservation, whereas the ECM served as permissive scaffolding but did not directly instruct stemness maintenance. The dynamic disruption of leukemic cells to the vascular integrity was recapitulated in this vascular niche model. Even though leukemic cells adhere to both ECs and MSCs, their adhesion to MSCs was the main niche factor maintaining leukemic stem cells and leading to chemoresistance in the bone marrow. Collectively, this bioengineered short-term static niche delineates the specific roles of dbECM as a structural foundation, ECs as spatial organizers, and MSCs as functional regulators, advancing our understanding of niche-directed physiology and pathology and accelerating the development of microenvironment-targeted therapies.
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DOI
高影响因子
Chinese Journal of Natural Medicines
·
2024
·
IF 4
Jiaorong QU,Xiaoyong XUE,Zhixing WANG,Zhi MA,Kexin JIA,Fanghong LI,Yinhao ZHANG,Ruiyu WU,Fei ZHOU,Piwen ZHAO,Xiaojiaoyang LI
ABSTRACT Liver fibrosis is a dynamic wound-healing response characterized by the agglutination of the extracellular matrix (ECM). Si-Wu-Tang (SWT), a traditional Chinese medicine (TCM) formula, is known for treating gynecological diseases and liver fibrosis. Our previous studies demonstrated that long non-coding RNA H19 (H19) was markedly upregulated in fibrotic livers while its deficiency markedly reversed fibrogenesis. However, the mechanisms by which SWT influences H19 remain unclear. Thus, we established a bile duct ligation (BDL)-induced liver fibrosis model to evaluate the hepatoprotective effects of SWT on various cells in the liver. Our results showed that SWT markedly improved ECM deposition and bile duct reactions in the liver. Notably, SWT relieved liver fibrosis by regulating the transcription of genes involved in the cytoskeleton remodeling, primarily in hepatic stellate cells (HSCs), and influencing cytoskeleton-related angiogenesis and hepatocellular injury. This modulation collectively led to reduced ECM deposition. Through extensive bioinformatics analyses, we determined that H19 acted as a miRNA sponge and mainly inhibited miR-200, miR-211, and let7b, thereby regulating the above cellular regulatory pathways. Meanwhile, SWT reversed H19-related miRNAs and signaling pathways, diminishing ECM deposition and liver fibrosis. However, these protective effects of SWT were diminished with the overexpression of H19 in vivo . In conclusion, our study elucidates the underlying mechanisms of SWT from the perspective of H19-related signal networks and proposes a potential SWT-based therapeutic strategy for the treatment of liver fibrosis.
研究领域:
药理学
·
分子生物学
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肝病学
·
传统中药
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DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Shuai-dong Chen,Chen-yu Chu,Chen-bing Wang,Yang Yang,Zhao-yu Xu,Yi-li Qu,Yi Man
Extracellular matrix (ECM) scaffold membranes have exhibited promising potential to better the outcomes of wound healing by creating a regenerative microenvironment around. However, when compared to the application in younger individuals, the performance of the same scaffold membrane in promoting re-epithelialization and collagen deposition was observed dissatisfying in aged mice. To comprehensively explore the mechanisms underlying this age-related disparity, we conducted the integrated analysis, combing single-cell RNA sequencing (scRNA-Seq) with spatial transcriptomics, and elucidated six functionally and spatially distinctive macrophage groups and lymphocytes surrounding the ECM scaffolds. Through intergroup comparative analysis and cell-cell communication, we characterized the dysfunction of Spp1+ macrophages in aged mice impeded the activation of the type Ⅱ immune response, thus inhibiting the repair ability of epidermal cells and fibroblasts around the ECM scaffolds. These findings contribute to a deeper understanding of biomaterial applications in varied physiological contexts, thereby paving the way for the development of precision-based biomaterials tailored specifically for aged individuals in future therapeutic strategies.
研究领域:
生物材料
·
伤口愈合
·
衰老
·
免疫学
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转录组学
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高影响因子
Journal of Materials Chemistry B
·
2022
·Vol. 10
·期 15
·2875-2888
·
IF 7.571
Yile Jia,Xianhui Zhang,Weihu Yang,Chuanchuan Lin,Bailong Tao,Zhiwen Deng,Pengfei Gao,Yulu Yang,Kaiyong Cai
Diabetes is a universal disease in the world. In the wounds of diabetic individuals, chronic inflammation and an inefficient fibrogenic process hinder the formation and deposition of the ECM, which delays the process of wound healing. To reconstruct the ECM of a diabetic patient's wound, in this work, we designed a pH-responsive “Double H-bonds” (hydrogen bond and hydrazone bond) hyaluronic acid–collagen hydrogel. This hydrogel can be self-gelled quickly in neutral and alkaline environments. But the weakly acidic inflammatory environment of diabetic wounds may accelerate the degradation of the hydrogel and the release of metformin. The in vitro results showed that the hydrogel can enhance the adhesion and infiltration of fibroblasts while inhibiting the growth of macrophages. Meanwhile, metformin could be released and polarize macrophages from M1 to M2, thereby accelerating the migration of fibroblasts and the production of collagen in a high glucose environment. The in vivo results proved that this hydrogel could remodel the ECM in diabetic mice wounds.
研究领域:
生物医学工程
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组织工程
·
伤口愈合
·
药学
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DOI
PubMed
高影响因子
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