NPJ REGENERATIVE MEDICINE 是一本新的开放获取、仅限在线的期刊，致力于发表最高质量的研究，以帮助人体修复、替换、恢复和再生受损组织和器官。

NPJ Regenerative Medicine is a new open-access, online-only journal dedicated to publishing high-quality research aimed at facilitating the repair, replacement, restoration, and regeneration of damaged tissues and organs in the human body.

NPJ Regenerative Medicine 是一本新的开放获取、仅限在线的期刊，专注于发表高质量的研究，旨在促进人体对受损组织和器官的修复、替换、恢复和再生。

npj Regenerative Medicine

Abstract Biomaterial-based cell replacement approaches to regenerative medicine are emerging as promising treatments for a wide array of profound clinical problems. Here we report an interpenetrating polymer network (IPN) composed of gelatin-hydroxyphenyl propionic acid and hyaluronic acid tyramine that is able to enhance intravitreal retinal cell therapy. By tuning our bioinspired hydrogel to mimic the vitreous chemical composition and mechanical characteristics we were able to improve in vitro and in vivo viability of human retinal ganglion cells (hRGC) incorporated into the IPN. In vivo vitreal injections of cell-bearing IPN in rats showed extensive attachment to the inner limiting membrane of the retina, improving with hydrogels stiffness. Engrafted hRGC displayed signs of regenerating processes along the optic nerve. Of note was the decrease in the immune cell response to hRGC delivered in the gel. The findings compel further translation of the gelatin-hyaluronic acid IPN for intravitreal cell therapy.

Pierre C. Dromel

Deepti Singh

Eliot Andres

Molly Likes

Motoichi Kurisawa

Alfredo Alexander-Katz

Myron Spector

Michael Young

A bioinspired gelatin-hyaluronic acid-based hybrid interpenetrating network for the enhancement of retinal ganglion cells replacement therapy

一种仿生明胶-透明质酸基杂化互穿网络用于增强视网膜神经节细胞替代疗法

Life expectancy has increased by three decades since the mid-twentieth century. Parallel healthspan expansion has however not followed, largely impeded by the pandemic of chronic diseases afflicting a growing older population. The lag in quality of life is a recognized challenge that calls for prioritization of disease-free longevity. Contemporary communal, clinical and research trends aspiring to extend the health horizon are here outlined in the context of an evolving epidemiology. A shared action integrating public and societal endeavors with emerging interventions that target age-related multimorbidity and frailty is needed. A multidimensional buildout of a curative perspective, boosted by modern anti-senescent and regenerative technology with augmented decision making, would require dedicated resources and cost-effective validation to responsibly bridge the healthspan-lifespan gap for a future of equitable global wellbeing.

Armin Garmany

Satsuki Yamada

Andre Terzic

Longevity leap: mind the healthspan gap

长寿跃进：关注健康寿命差距

Maxillofacial hard tissue defects caused by trauma or infection often affect craniofacial function. Taking the natural hard tissue structure as a template, constructing an engineered tissue repair module is an important scheme to realize the functional regeneration and repair of maxillofacial hard tissue. Here, inspired by the biomineralization process, we constructed a composite mineral matrix hydrogel PAA-CMC-TDM containing amorphous calcium phosphates (ACPs), polyacrylic acid (PAA), carboxymethyl chitosan (CMC) and dentin matrix (TDM). The dynamic network composed of Ca2+·COO- coordination and ACPs made the hydrogel loaded with TDM, and exhibited self-repairing ability and injectability. The mechanical properties of PAA-CMC-TDM can be regulated, but the functional activity of TDM remains unaffected. Cytological studies and animal models of hard tissue defects show that the hydrogel can promote the odontogenesis or osteogenic differentiation of mesenchymal stem cells, adapt to irregular hard tissue defects, and promote in situ regeneration of defective tooth and bone tissues. In summary, this paper shows that the injectable TDM hydrogel based on biomimetic mineralization theory can induce hard tissue formation and promote dentin/bone regeneration.

Bo Wen

Yuguo Dai

Xue Han

Fangjun Huo

Li Xie

Mei Yu

Yuru Wang

Ning An

Zhonghan Li

Weihua Guo

npj Regen Med

Biomineralization-inspired mineralized hydrogel promotes the repair and regeneration of dentin/bone hard tissue

仿生矿化水凝胶促进牙本质/骨硬组织修复与再生

Abstract Adult bone regeneration is orchestrated by the precise actions of osteoprogenitor cells (OPCs). However, the mechanisms by which OPC proliferation and differentiation are linked and thereby regulated are yet to be defined. Here, we present evidence that during intramembranous bone formation OPC proliferation is controlled by Notch signaling, while differentiation is initiated by activation of canonical Wnt signaling. The temporospatial separation of Notch and Wnt signal activation during the early stages of bone regeneration suggests crosstalk between the two pathways. In vitro and in vivo manipulation of the two essential pathways demonstrate that Wnt activation leads to initiation of osteogenic differentiation and at the same time inhibits Notch signaling, which results in termination of the proliferative phase. Here, we establish canonical Wnt signaling as a key regulator that facilitates the crosstalk between OPC proliferation and differentiation during intramembranous, primary bone healing.

S. Lee

L. H. Remark

A. M. Josephson

K. Leclerc

E. Muiños Lopez

D. J. Kirby

Devan Mehta

H. P. Litwa

M. Z. Wong

S. Y. Shin

P. Leucht

Notch-Wnt signal crosstalk regulates proliferation and differentiation of osteoprogenitor cells during intramembranous bone healing

Notch-Wnt信号交叉对话调控膜内骨愈合过程中成骨祖细胞的增殖与分化

Heart failure (HF) is a major cause of mortality and morbidity worldwide, yet with limited therapeutic options. Cardiac bridging integrator 1 (cBIN1), a cardiomyocyte transverse-tubule (t-tubule) scaffolding protein which organizes the calcium handling machinery, is transcriptionally reduced in HF and can be recovered for functional rescue in mice. Here we report that in human patients with HF with reduced ejection fraction (HFrEF), left ventricular cBIN1 levels linearly correlate with organ-level ventricular remodeling such as diastolic diameter. Using a minipig model of right ventricular tachypacing-induced non-ischemic dilated cardiomyopathy and chronic HFrEF, we identified that a single intravenous low dose (6 × 10

Jing Li

Pia Balmaceda

Thuy Ha

Joseph R Visker

Nicole Maalouf

Eugene Kwan

Guillaume L Hoareau

Michel Accad

Ravi Ranjan

Craig H Selzman

Stavros G Drakos

Robin M Shaw

TingTing Hong

Cardiac bridging integrator 1 gene therapy rescues chronic non-ischemic heart failure in minipigs

心脏桥接整合子1基因疗法可挽救小型猪慢性非缺血性心力衰竭

Many studies have explored different loading and rehabilitation strategies, yet rehabilitation intensity and its impact on the local strain environment and bone healing have largely not been investigated. This study combined implantable strain sensors and subject-specific finite element models in a 2 mm rodent segmental bone defect model. After injury animals were underwent high or low intensity rehabilitation. High intensity rehabilitation increased local strains within the regenerative niche by an average of 44% compared to the low intensity rehabilitation. Finite element modeling demonstrated that resistance rehabilitation significantly increased compressive strain by a factor of 2.0 at week 2 and 4.45 after 4 weeks of rehabilitation. Animals that underwent resistance running had the greatest bone volume and improved functional recovery with regenerated femurs that matched intact failure torque and torsional stiffness values. These results demonstrate the potential for early resistance rehabilitation to improve bone healing.

Kylie E. Williams

Julia Andraca Harrer

Steven A. LaBelle

Kelly Leguineche

Jarred Kaiser

Salil Karipott

Angela Lin

Alyssa Vongphachanh

Travis Fulton

J. Walker Rosenthal

Farhan Muhib

Keat Ghee Ong

Jeffrey A. Weiss

Nick J. Willett

Robert E. Guldberg

Early resistance rehabilitation improves functional regeneration following segmental bone defect injury

早期抗阻康复改善节段性骨缺损损伤后的功能再生

Abstract Cutaneous exposure to the DNA alkylating class of chemotherapeutic agents including nitrogen mustard (NM) leads to both skin injury and systemic inflammation. Circulating myeloid subsets recruited to the skin act to further exacerbate local tissue damage while interfering with the wound healing process. We demonstrate herein that intravenous delivery of p oly( l actic- co - g lycolic acid) i mmune- m odifying nano p articles (PLGA-IMPs) shortly after NM exposure restricts accumulation of macrophages and inflammatory monocytes at the injury site, resulting in attenuated skin pathology. Furthermore, PLGA-IMPs induce an early influx and local enrichment of Foxp3 + regulatory T cells (Treg) in the skin lesions critical for the suppression of myeloid cell-pro-inflammatory responses via induction of IL-10 and TGF-β in the cutaneous milieu. Functional depletion of CD4 + Tregs ablates the efficacy of PLGA-IMPs accompanied by a loss of local accumulation of anti-inflammatory cytokines essential for wound healing. Thus, in severe skin trauma, PLGA-IMPs may have therapeutic potential via modulation of inflammatory myeloid cells and regulatory T lymphocytes.

Ummiye V. Onay

Dan Xu

Dauren Biyashev

Spencer T. Evans

Michael M. Demczuk

Tobias Neef

Joseph R. Podojil

Sara Beddow

Nathan C. Gianneschi

I. Caroline Le Poole

Stephen D. Miller

Kurt Q. Lu

Attenuation of skin injury by a MARCO targeting PLGA nanoparticle

靶向MARCO的PLGA纳米颗粒减轻皮肤损伤

The precise mechanisms regulating inflammatory and prorepair macrophages have not been fully elucidated, despite the pivotal role played by innate immunity in wound healing. We first employed a denervation wound model to validate the crosstalk between neurons and macrophages. Compared to normal wound healing, the denervation wound healing process involved fewer macrophages, decreased angiogenesis, and delayed wound healing. Consistent with the results of the scRNA-seq libraries, the number of early-phase wound proinflammatory and late-phase wound prorepair macrophages were decreased during the denervation wound healing process. We profiled early-phase and late-phase skin wounds in mice at the transcriptional and functional levels and compared them to those of normal wounds. We revealed a neuroimmune regulatory pathway driven by peripheral nerve-derived CSF1 that induces BMP2 expression in prorepair macrophages and enhances nerve regeneration. Crosstalk between neurons and macrophages facilitates the healing process of wounds and provides a potential strategy for wound healing therapy.

Kai Wang

Binyu Song

Yuhan Zhu

Juanli Dang

Tong Wang

Yajuan Song

Yi Shi

Shuang You

Sijia Li

Zhou Yu

Baoqiang Song

Peripheral nerve-derived CSF1 induces BMP2 expression in macrophages to promote nerve regeneration and wound healing

外周神经来源的CSF1诱导巨噬细胞表达BMP2以促进神经再生和伤口愈合

Abstract Cardiac regenerative potential in the animal kingdom displays striking divergence across ontogeny and phylogeny. Here we discuss several fundamental questions in heart regeneration and provide both a holistic view of heart regeneration in the organism as a whole, as well as a single-cell perspective on intercellular communication among diverse cardiac cell populations. We hope to provide valuable insights that advance our understanding of organ regeneration and future therapeutic strategies.

Xiaoxin Chen

Xiaochen Zhong

Guo N Huang

Heart regeneration from the whole-organism perspective to single-cell resolution

从整体生物视角到单细胞分辨率的心脏再生

Abbreviation	npj Regen Med
Journal Impact	6.37
Quartiles(Global)	ENGINEERING, BIOMEDICAL(Q1)

ISSN	2057-3995
h-index	37

Publication Information	Publisher: Nature Publishing Group，Publishing cycle: ，Journal Type: journal，Open Access Journals: Yes
Basic data	Year of publication: 2016，Proportion of original research papers: 89.19%，Self Citation Rate:1.60%， Gold OA Rate: 99.54%
Journal Fees	$3890Details
Average review cycle	网友分享经验：12 Weeks

npj Regenerative Medicine

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A bioinspired gelatin-hyaluronic acid-based hybrid interpenetrating network for the enhancement of retinal ganglion cells replacement therapy

Longevity leap: mind the healthspan gap

Biomineralization-inspired mineralized hydrogel promotes the repair and regeneration of dentin/bone hard tissue

Notch-Wnt signal crosstalk regulates proliferation and differentiation of osteoprogenitor cells during intramembranous bone healing

Cardiac bridging integrator 1 gene therapy rescues chronic non-ischemic heart failure in minipigs

Early resistance rehabilitation improves functional regeneration following segmental bone defect injury

Cardiac bridging integrator 1 gene therapy rescues chronic non-ischemic heart failure in minipigs

Attenuation of skin injury by a MARCO targeting PLGA nanoparticle

Peripheral nerve-derived CSF1 induces BMP2 expression in macrophages to promote nerve regeneration and wound healing

Heart regeneration from the whole-organism perspective to single-cell resolution