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Yu Ru Shih

Assistant Professor of Orthopaedic Surgery
Orthopaedic Surgery

Selected Publications


Multi-Functional Small Molecule Alleviates Fracture Pain and Promotes Bone Healing.

Journal Article Adv Sci (Weinh) · December 2023 Bone injuries such as fractures are one major cause of morbidities worldwide. A considerable number of fractures suffer from delayed healing, and the unresolved acute pain may transition to chronic and maladaptive pain. Current management of pain involves ... Full text Open Access Link to item Cite

General versus Neuraxial Anesthesia on Clinical Outcomes in Patients Receiving Hip Fracture Surgery: An Analysis of the ACS NSQIP Database

Journal Article Journal of Clinical Medicine · June 1, 2023 Whether the use of neuraxial anesthesia or general anesthesia leads to more favorable postoperative outcomes in patients receiving hip fracture surgery remains unclear. We used data from the American College of Surgeons National Surgical Quality Improvemen ... Full text Cite

Preoperative renal insufficiency predicts postoperative adverse outcomes in a mixed surgical population: a retrospective matched cohort study using the NSQIP database.

Journal Article Int J Surg · April 1, 2023 BACKGROUND: The incidence of chronic kidney disease is increasing, but most cases are not diagnosed until the accidental finding of abnormal laboratory data or the presentation of severe symptoms. Patients with chronic kidney disease are reported to have a ... Full text Link to item Cite

pH-Sensitive nanocarrier assisted delivery of adenosine to treat osteoporotic bone loss.

Journal Article Biomater Sci · September 13, 2022 Bone tissue undergoes continuous remodeling via osteoclast-mediated bone resorption and osteoblast-mediated bone formation. An imbalance in this process with enhanced osteoclastic activity can lead to excessive bone resorption, resulting in bone thinning. ... Full text Link to item Cite

Molecularly Tailored Interface for Long-Term Xenogeneic Cell Transplantation.

Journal Article Adv Funct Mater · January 19, 2022 Encapsulation of therapeutic cells in a semipermeable device can mitigate the need for systemic immune suppression following cell transplantation by providing local immunoprotection while being permeable to nutrients, oxygen, and different cell-secreted bi ... Full text Link to item Cite

Resolution of inflammation in bone regeneration: From understandings to therapeutic applications.

Journal Article Biomaterials · October 2021 Featured Publication Impaired bone healing occurs in 5-10% of cases following injury, leading to a significant economic and clinical impact. While an inflammatory response upon injury is necessary to facilitate healing, its resolution is critical for bone tissue repair as elev ... Full text Link to item Cite

Bone targeting nanocarrier-assisted delivery of adenosine to combat osteoporotic bone loss.

Journal Article Biomaterials · June 2021 Featured Publication Extracellular adenosine has been shown to play a key role in maintaining bone health and could potentially be used to treat bone loss. However, systemic administration of exogenous adenosine to treat bone disorders remains a challenge due to the ubiquitous ... Full text Link to item Cite

In Vivo Sequestration of Innate Small Molecules to Promote Bone Healing.

Journal Article Adv Mater · February 2020 Approaches that enable innate repair mechanisms hold great potential for tissue repair. Herein, biomaterial-assisted sequestration of small molecules is described to localize pro-regenerative signaling at the injury site. Specifically, a synthetic biomater ... Full text Link to item Cite

Dysregulation of ectonucleotidase-mediated extracellular adenosine during postmenopausal bone loss.

Journal Article Sci Adv · August 2019 Featured Publication Adenosine and its receptors play a key role in bone homeostasis and regeneration. Extracellular adenosine is generated from CD39 and CD73 activity in the cell membrane, through conversion of adenosine triphosphate to adenosine monophosphate (AMP) and AMP t ... Full text Link to item Cite

Tissue engineered bone mimetics to study bone disorders ex vivo: Role of bioinspired materials.

Journal Article Biomaterials · April 2019 Recent advances in materials development and tissue engineering has resulted in a substantial number of bioinspired materials that recapitulate cardinal features of bone extracellular matrix (ECM) such as dynamic inorganic and organic environment(s), hiera ... Full text Link to item Cite

In vivo RNA editing of point mutations via RNA-guided adenosine deaminases.

Journal Article Nat Methods · March 2019 We present in vivo sequence-specific RNA base editing via adenosine deaminases acting on RNA (ADAR) enzymes with associated ADAR guide RNAs (adRNAs). To achieve this, we systematically engineered adRNAs to harness ADARs, and comprehensively evaluated the s ... Full text Link to item Cite

Phenylboronic Acid-polymers for Biomedical Applications.

Journal Article Curr Med Chem · 2019 BACKGROUND: Phenylboronic acid-polymers (PBA-polymers) have attracted tremendous attention as potential stimuli-responsive materials with applications in drug-delivery depots, scaffolds for tissue engineering, HIV barriers, and biomolecule-detecting/sensin ... Full text Link to item Cite

Effect of age on biomaterial-mediated in situ bone tissue regeneration.

Journal Article Acta Biomater · September 15, 2018 UNLABELLED: Emerging studies show the potential application of synthetic biomaterials that are intrinsically osteoconductive and osteoinductive as bone grafts to treat critical bone defects. Here, the biomaterial not only assists recruitment of endogenous ... Full text Link to item Cite

Macroporous Dual-compartment Hydrogels for Minimally Invasive Transplantation of Primary Human Hepatocytes.

Journal Article Transplantation · September 2018 BACKGROUND: Given the shortage of available organs for whole or partial liver transplantation, hepatocyte cell transplantation has long been considered a potential strategy to treat patients suffering from various liver diseases. Some of the earliest appro ... Full text Link to item Cite

In Situ Gene Therapy via AAV-CRISPR-Cas9-Mediated Targeted Gene Regulation.

Journal Article Mol Ther · July 5, 2018 Development of efficacious in vivo delivery platforms for CRISPR-Cas9-based epigenome engineering will be critical to enable the ability to target human diseases without permanent modification of the genome. Toward this, we utilized split-Cas9 systems to d ... Full text Link to item Cite

Mineralized Biomaterials Mediated Repair of Bone Defects Through Endogenous Cells.

Journal Article Tissue Eng Part A · July 2018 Synthetic biomaterials that create a dynamic calcium (Ca2+)-, phosphate (PO43-) ion-, and calcium phosphate (CaP)-rich microenvironment, similar to that found in native bone tissue, have been shown to promote osteogenic commitment of stem cells in vitro an ... Full text Link to item Cite

Direct Conversion of Human Pluripotent Stem Cells to Osteoblasts With a Small Molecule.

Journal Article Curr Protoc Stem Cell Biol · February 28, 2018 Human pluripotent stem cells (hPSCs), which exhibit unlimited self-renewal ability and can differentiate into all cell types in the human body, are a promising cell source for cell-based therapies and regenerative medicine. Small molecules hold great poten ... Full text Link to item Cite

In vivo engineering of bone tissues with hematopoietic functions and mixed chimerism.

Journal Article Proc Natl Acad Sci U S A · May 23, 2017 Featured Publication Synthetic biomimetic matrices with osteoconductivity and osteoinductivity have been developed to regenerate bone tissues. However, whether such systems harbor donor marrow in vivo and support mixed chimerism remains unknown. We devised a strategy to engine ... Full text Link to item Cite

Biomineralized matrices as intelligent scaffolds for bone tissue regeneration

Chapter · January 1, 2017 Bone is an example of a biomineralized functional living tissue. The mineralized components of bone tissue endow them with unique mechanical and chemical functions. Specifically, bone tissue is composed of inorganic calcium phosphate (CaP)-rich mineralized ... Full text Cite

Multi-Functional Small Molecule Alleviates Fracture Pain and Promotes Bone Healing.

Journal Article Adv Sci (Weinh) · December 2023 Bone injuries such as fractures are one major cause of morbidities worldwide. A considerable number of fractures suffer from delayed healing, and the unresolved acute pain may transition to chronic and maladaptive pain. Current management of pain involves ... Full text Open Access Link to item Cite

General versus Neuraxial Anesthesia on Clinical Outcomes in Patients Receiving Hip Fracture Surgery: An Analysis of the ACS NSQIP Database

Journal Article Journal of Clinical Medicine · June 1, 2023 Whether the use of neuraxial anesthesia or general anesthesia leads to more favorable postoperative outcomes in patients receiving hip fracture surgery remains unclear. We used data from the American College of Surgeons National Surgical Quality Improvemen ... Full text Cite

Preoperative renal insufficiency predicts postoperative adverse outcomes in a mixed surgical population: a retrospective matched cohort study using the NSQIP database.

Journal Article Int J Surg · April 1, 2023 BACKGROUND: The incidence of chronic kidney disease is increasing, but most cases are not diagnosed until the accidental finding of abnormal laboratory data or the presentation of severe symptoms. Patients with chronic kidney disease are reported to have a ... Full text Link to item Cite

pH-Sensitive nanocarrier assisted delivery of adenosine to treat osteoporotic bone loss.

Journal Article Biomater Sci · September 13, 2022 Bone tissue undergoes continuous remodeling via osteoclast-mediated bone resorption and osteoblast-mediated bone formation. An imbalance in this process with enhanced osteoclastic activity can lead to excessive bone resorption, resulting in bone thinning. ... Full text Link to item Cite

Molecularly Tailored Interface for Long-Term Xenogeneic Cell Transplantation.

Journal Article Adv Funct Mater · January 19, 2022 Encapsulation of therapeutic cells in a semipermeable device can mitigate the need for systemic immune suppression following cell transplantation by providing local immunoprotection while being permeable to nutrients, oxygen, and different cell-secreted bi ... Full text Link to item Cite

Resolution of inflammation in bone regeneration: From understandings to therapeutic applications.

Journal Article Biomaterials · October 2021 Featured Publication Impaired bone healing occurs in 5-10% of cases following injury, leading to a significant economic and clinical impact. While an inflammatory response upon injury is necessary to facilitate healing, its resolution is critical for bone tissue repair as elev ... Full text Link to item Cite

Bone targeting nanocarrier-assisted delivery of adenosine to combat osteoporotic bone loss.

Journal Article Biomaterials · June 2021 Featured Publication Extracellular adenosine has been shown to play a key role in maintaining bone health and could potentially be used to treat bone loss. However, systemic administration of exogenous adenosine to treat bone disorders remains a challenge due to the ubiquitous ... Full text Link to item Cite

In Vivo Sequestration of Innate Small Molecules to Promote Bone Healing.

Journal Article Adv Mater · February 2020 Approaches that enable innate repair mechanisms hold great potential for tissue repair. Herein, biomaterial-assisted sequestration of small molecules is described to localize pro-regenerative signaling at the injury site. Specifically, a synthetic biomater ... Full text Link to item Cite

Dysregulation of ectonucleotidase-mediated extracellular adenosine during postmenopausal bone loss.

Journal Article Sci Adv · August 2019 Featured Publication Adenosine and its receptors play a key role in bone homeostasis and regeneration. Extracellular adenosine is generated from CD39 and CD73 activity in the cell membrane, through conversion of adenosine triphosphate to adenosine monophosphate (AMP) and AMP t ... Full text Link to item Cite

Tissue engineered bone mimetics to study bone disorders ex vivo: Role of bioinspired materials.

Journal Article Biomaterials · April 2019 Recent advances in materials development and tissue engineering has resulted in a substantial number of bioinspired materials that recapitulate cardinal features of bone extracellular matrix (ECM) such as dynamic inorganic and organic environment(s), hiera ... Full text Link to item Cite

In vivo RNA editing of point mutations via RNA-guided adenosine deaminases.

Journal Article Nat Methods · March 2019 We present in vivo sequence-specific RNA base editing via adenosine deaminases acting on RNA (ADAR) enzymes with associated ADAR guide RNAs (adRNAs). To achieve this, we systematically engineered adRNAs to harness ADARs, and comprehensively evaluated the s ... Full text Link to item Cite

Phenylboronic Acid-polymers for Biomedical Applications.

Journal Article Curr Med Chem · 2019 BACKGROUND: Phenylboronic acid-polymers (PBA-polymers) have attracted tremendous attention as potential stimuli-responsive materials with applications in drug-delivery depots, scaffolds for tissue engineering, HIV barriers, and biomolecule-detecting/sensin ... Full text Link to item Cite

Effect of age on biomaterial-mediated in situ bone tissue regeneration.

Journal Article Acta Biomater · September 15, 2018 UNLABELLED: Emerging studies show the potential application of synthetic biomaterials that are intrinsically osteoconductive and osteoinductive as bone grafts to treat critical bone defects. Here, the biomaterial not only assists recruitment of endogenous ... Full text Link to item Cite

Macroporous Dual-compartment Hydrogels for Minimally Invasive Transplantation of Primary Human Hepatocytes.

Journal Article Transplantation · September 2018 BACKGROUND: Given the shortage of available organs for whole or partial liver transplantation, hepatocyte cell transplantation has long been considered a potential strategy to treat patients suffering from various liver diseases. Some of the earliest appro ... Full text Link to item Cite

In Situ Gene Therapy via AAV-CRISPR-Cas9-Mediated Targeted Gene Regulation.

Journal Article Mol Ther · July 5, 2018 Development of efficacious in vivo delivery platforms for CRISPR-Cas9-based epigenome engineering will be critical to enable the ability to target human diseases without permanent modification of the genome. Toward this, we utilized split-Cas9 systems to d ... Full text Link to item Cite

Mineralized Biomaterials Mediated Repair of Bone Defects Through Endogenous Cells.

Journal Article Tissue Eng Part A · July 2018 Synthetic biomaterials that create a dynamic calcium (Ca2+)-, phosphate (PO43-) ion-, and calcium phosphate (CaP)-rich microenvironment, similar to that found in native bone tissue, have been shown to promote osteogenic commitment of stem cells in vitro an ... Full text Link to item Cite

Direct Conversion of Human Pluripotent Stem Cells to Osteoblasts With a Small Molecule.

Journal Article Curr Protoc Stem Cell Biol · February 28, 2018 Human pluripotent stem cells (hPSCs), which exhibit unlimited self-renewal ability and can differentiate into all cell types in the human body, are a promising cell source for cell-based therapies and regenerative medicine. Small molecules hold great poten ... Full text Link to item Cite

In vivo engineering of bone tissues with hematopoietic functions and mixed chimerism.

Journal Article Proc Natl Acad Sci U S A · May 23, 2017 Featured Publication Synthetic biomimetic matrices with osteoconductivity and osteoinductivity have been developed to regenerate bone tissues. However, whether such systems harbor donor marrow in vivo and support mixed chimerism remains unknown. We devised a strategy to engine ... Full text Link to item Cite

Biomineralized matrices as intelligent scaffolds for bone tissue regeneration

Chapter · January 1, 2017 Bone is an example of a biomineralized functional living tissue. The mineralized components of bone tissue endow them with unique mechanical and chemical functions. Specifically, bone tissue is composed of inorganic calcium phosphate (CaP)-rich mineralized ... Full text Cite

Small molecule-driven direct conversion of human pluripotent stem cells into functional osteoblasts.

Journal Article Sci Adv · August 2016 The abilities of human pluripotent stem cells (hPSCs) to proliferate without phenotypic alteration and to differentiate into tissue-specific progeny make them a promising cell source for regenerative medicine and development of physiologically relevant in ... Full text Link to item Cite

A Single-Cell Assay for Time Lapse Studies of Exosome Secretion and Cell Behaviors.

Journal Article Small · July 2016 To understand the inhomogeneity of cells in biological systems, there is a growing demand on the capability of characterizing the properties of individual single cells. Since single-cell studies require continuous monitoring of the cell behaviors, an effec ... Full text Link to item Cite

In vivo comparison of biomineralized scaffold-directed osteogenic differentiation of human embryonic and mesenchymal stem cells.

Journal Article Drug Deliv Transl Res · April 2016 Human pluripotent stem cells such as embryonic stem cells (hESCs) and multipotent stem cells like mesenchymal stem cells (hMSCs) hold great promise as potential cell sources for bone tissue regeneration. Comparing the in vivo osteogenesis of hESCs and hMSC ... Full text Link to item Cite

Synthetic bone mimetic matrix-mediated in situ bone tissue formation through host cell recruitment.

Journal Article Acta Biomater · June 2015 Advances in tissue engineering have offered new opportunities to restore anatomically and functionally compromised tissues. Although traditional tissue engineering approaches that utilize biomaterials and cells to create tissue constructs for implantation ... Full text Link to item Cite

Biomineralized matrices dominate soluble cues to direct osteogenic differentiation of human mesenchymal stem cells through adenosine signaling.

Journal Article Biomacromolecules · March 9, 2015 Stem cell differentiation is determined by a repertoire of signals from its microenvironment, which includes the extracellular matrix (ECM) and soluble cues. The ability of mesenchymal stem cells (MSCs), a common precursor for the skeletal system, to diffe ... Full text Link to item Cite

Adenosine signaling mediates osteogenic differentiation of human embryonic stem cells on mineralized matrices

Journal Article Frontiers in Bioengineering and Biotechnology · January 1, 2015 Human embryonic stem cells (hESCs) are attractive cell sources for tissue engineering and regenerative medicine due to their self-renewal and differentiation ability. Design of biomaterials with an intrinsic ability that promotes hESC differentiation to th ... Full text Cite

Mineralized gelatin methacrylate-based matrices induce osteogenic differentiation of human induced pluripotent stem cells.

Journal Article Acta Biomater · December 2014 Human induced pluripotent stem cells (hiPSC) are a promising cell source with pluripotency and self-renewal properties. Design of simple and robust biomaterials with an innate ability to induce lineage-specificity of hiPSC is desirable to realize their app ... Full text Link to item Cite

Tendon and ligament tissue engineering

Chapter · November 5, 2014 Stem Cell Biology and Tissue Engineering in Dental Sciences bridges the gap left by many tissue engineering and stem cell biology titles to highlight the significance of translational research in this field in the medical sciences. ... Cite

Biomineralized matrix-assisted osteogenic differentiation of human embryonic stem cells

Journal Article Journal of Materials Chemistry B · September 14, 2014 The physical and chemical properties of a matrix play an important role in determining various cellular behaviors, including lineage specificity. We demonstrate that the differentiation commitment of human embryonic stem cells (hESCs), both in vitro and in ... Full text Cite

WNT3A promotes myogenesis of human embryonic stem cells and enhances in vivo engraftment.

Journal Article Sci Rep · August 1, 2014 The ability of human embryonic stem cells (hESCs) to differentiate into skeletal muscle cells is an important criterion in using them as a cell source to ameliorate skeletal muscle impairments. However, differentiation of hESCs into skeletal muscle cells s ... Full text Link to item Cite

Adjunctive traditional Chinese medicine therapy improves survival in patients with advanced breast cancer: A population‐based study

Journal Article Cancer · May 2014 BACKGROUNDTraditional Chinese medicine (TCM) is one of the most common complementary and alternative medicines used in the treatment of patients with breast cancer. However, the clinical effect of TCM on survival, ... Full text Cite

Calcium phosphate-bearing matrices induce osteogenic differentiation of stem cells through adenosine signaling.

Journal Article Proc Natl Acad Sci U S A · January 21, 2014 Featured Publication Synthetic matrices emulating the physicochemical properties of tissue-specific ECMs are being developed at a rapid pace to regulate stem cell fate. Biomaterials containing calcium phosphate (CaP) moieties have been shown to support osteogenic differentiati ... Full text Link to item Cite

Human mesenchymal stem cells suppress the stretch-induced inflammatory miR-155 and cytokines in bronchial epithelial cells.

Journal Article PLoS One · 2013 Current research in pulmonary pathology has focused on inflammatory reactions initiated by immunological responses to allergens and irritants. In addition to these biochemical stimuli, physical forces also play an important role in regulating the structure ... Full text Link to item Cite

Mineralized synthetic matrices as an instructive microenvironment for osteogenic differentiation of human mesenchymal stem cells.

Journal Article Macromol Biosci · August 2012 The effect of substrate-mediated signals on osteogenic differentiation of hMSCs is studied using a synthetic bone-like material comprising both organic and inorganic components that supports adhesion, spreading, and proliferation of hMSCs. hMSCs undergo os ... Full text Link to item Cite

Regulation of the fate of human mesenchymal stem cells by mechanical and stereo-topographical cues provided by silicon nanowires.

Journal Article Biomaterials · July 2012 Extracellular stimuli imposed on stem cells enable efficient initiation of mechanotransductive signaling to regulate stem cell fates; however, how such physical cues conferred by the stereo-topographical matrix govern the fate of stem cells still remains u ... Full text Link to item Cite

Phosphoproteomic analysis of human mesenchymal stromal cells during osteogenic differentiation.

Journal Article J Proteome Res · February 3, 2012 Human mesenchymal stromal cells (hMSCs) are promising candidates for cell therapy and tissue regeneration. Knowledge of the molecular mechanisms governing hMSC commitment into osteoblasts is critical to the development of therapeutic applications for human ... Full text Link to item Cite

Hypoxia promotes proliferation and osteogenic differentiation potentials of human mesenchymal stem cells.

Journal Article J Orthop Res · February 2012 Mesenchymal stem cells (MSCs), which can be isolated from bone marrow and other somatic tissues, are residing in an environment with relative low oxygen tension. The purpose of this study is to investigate the effects of hypoxia on MSCs, and we hypothesize ... Full text Link to item Cite

Matrix stiffness regulation of integrin-mediated mechanotransduction during osteogenic differentiation of human mesenchymal stem cells.

Journal Article J Bone Miner Res · April 2011 Featured Publication Mesenchymal stem cells (MSCs) cultured on extracellular matrices with different stiffness have been shown to possess diverse lineage commitment owing to the extracellular mechanical stimuli sensed by the cells. The aim of this study was to further delineat ... Full text Link to item Cite

Isolation and characterization of stem cells from the human parathyroid gland.

Journal Article Cell Prolif · August 2009 OBJECTIVES: Somatic stem cells can be obtained from a variety of adult human tissues. However, it was not clear whether human parathyroid glands, which secrete parathyroid hormones and are essential in maintaining homeostasis levels of calcium ions in the ... Full text Link to item Cite

Stem cell therapy for liver disease: parameters governing the success of using bone marrow mesenchymal stem cells.

Journal Article Gastroenterology · June 2008 BACKGROUND & AIMS: Liver transplantation is the primary treatment for various end-stage hepatic diseases but is hindered by the lack of donor organs and by complications associated with rejection and immunosuppression. There is increasing evidence to sugge ... Full text Link to item Cite

Coordinated changes of mitochondrial biogenesis and antioxidant enzymes during osteogenic differentiation of human mesenchymal stem cells.

Journal Article Stem Cells · April 2008 The multidifferentiation ability of mesenchymal stem cells holds great promise for cell therapy. Numerous studies have focused on the establishment of differentiation protocols, whereas little attention has been paid to the metabolic changes during the dif ... Full text Link to item Cite

Internalization is essential for the antiapoptotic effects of exogenous thymosin beta-4 on human corneal epithelial cells.

Journal Article Invest Ophthalmol Vis Sci · January 2007 PURPOSE: Exogenous thymosin beta-4 (Tbeta(4)) has been shown to inhibit the apoptosis in nontransformed human corneal epithelial cells that is triggered by ethanol. The purpose of this study is to examine whether exogenous Tbeta(4) protects SV40-immortaliz ... Full text Link to item Cite

Growth of mesenchymal stem cells on electrospun type I collagen nanofibers.

Journal Article Stem Cells · November 2006 We reconstituted type I collagen nanofibers prepared by electrospin technology and examined the morphology, growth, adhesion, cell motility, and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (MSCs) on three nano-sized diame ... Full text Link to item Cite