Eben Alsberg - Academia.edu (original) (raw)
Papers by Eben Alsberg
Advanced Functional Materials, 2013
Advanced Healthcare Materials, 2015
Giving rise to both bone and cartilage during development, bone marrow-derived mesenchymal stem c... more Giving rise to both bone and cartilage during development, bone marrow-derived mesenchymal stem cells (hMSC) have the unique capacity to generate the complex tissues of the osteochondral interface. Utilizing a scaffold-free hMSC system, biphasic osteochondral constructs are incorporated with two types of growth factor-releasing microparticles to enable spatially organized differentiation. Gelatin microspheres (GM) releasing transforming growth factor-β1 (TGF-β1) combined with hMSC form the chondrogenic phase. The osteogenic phase contains hMSC only, mineral-coated hydroxyapatite microparticles (MCM), or MCM loaded with bone morphogenetic protein-2 (BMP-2), cultured in medium with or without BMP-2. After 4 weeks, TGF-β1 release from GM within the cartilage phase promotes formation of a glycosaminoglycan- and type II collagen-rich matrix, and has a local inhibitory effect on osteogenesis. In the osteogenic phase, type X collagen and osteopontin are produced in all conditions. However, calcification occurs on the outer edges of the chondrogenic phase in some constructs cultured in media containing BMP-2, and alkaline phosphatase levels are elevated, indicating that BMP-2 releasing MCM provides better control over region-specific differentiation. The production of complex, stem cell-derived osteochondral tissues via incorporated microparticles could enable earlier implantation, potentially improving outcomes in the treatment of osteochondral defects.
There issubstantial needforthereplacement oftissues inthecraniofacial complex duetocongenital def... more There issubstantial needforthereplacement oftissues inthecraniofacial complex duetocongenital defects, disease, andinjury. Thefield oftissue engineering, through theapplication ofengineering andbiological principles, hasthepotential tocre- atefunctional replacements fordamaged orpathologic tissues. Three mainapproaches totissue engineering havebeenpursued conduction, induction bybioactive factors, andcell transplantation. These approaches will bereviewed asthey havebeenapplied tokeytissues inthecraniofacial region. While manyobstacles muststill beovercome prior tothesuccessful clinical restoration of tissues suchasskeletal muscle andthesalivary glands, significant progress hasbeenachieved inthedevelopment ofseveral tissue equivalents, including skin, bone, andcartilage. Thecombined technologies ofgenetherapy anddrug delivery withcell transplan- tation will continue toincrease treatment options for craniofacial cosmetic andfunctional restoration.
Physical Review E, 2009
Aggregation in nondiffusion limited colloidal particle suspensions follows a temporal power-law d... more Aggregation in nondiffusion limited colloidal particle suspensions follows a temporal power-law dependence that is consistent with classical diffusion limited cluster aggregation models; however, the dynamic scaling exponents observed in these systems are not adequately described by diffusion limited cluster aggregation models, which expect these scaling exponents to be constant over all experimental conditions. We show here that the dynamic scaling
ISSCC. 2005 IEEE International Digest of Technical Papers. Solid-State Circuits Conference, 2005., 2005
Advanced healthcare materials, 2015
By silencing specific gene expression, short interfering RNA (siRNA) is a potent biomolecule for ... more By silencing specific gene expression, short interfering RNA (siRNA) is a potent biomolecule for regulating cell behavior in tissue engineering applications, and spatially patterning its presentation to cells may ultimately facilitate the engineering of complex tissues. The study by E. Alsberg and team on page 714 demonstrates a hydrogel system that presents a linear gradient of siRNA to encapsulated cells, inducing a spatial gradient of green fluorescent protein expression.
Biomaterials, 2015
There is a critical need to engineer a neotrachea because currently there are no long-term treatm... more There is a critical need to engineer a neotrachea because currently there are no long-term treatments for tracheal stenoses affecting large portions of the airway. In this work, a modular tracheal tissue replacement strategy was developed. High-cell density, scaffold-free human mesenchymal stem cell-derived cartilaginous rings and tubes were successfully generated through employment of custom designed culture wells and a ring-to-tube assembly system. Furthermore, incorporation of transforming growth factor-β1-delivering gelatin microspheres into the engineered tissues enhanced chondrogenesis with regard to tissue size and matrix production and distribution in the ring- and tube-shaped constructs, as well as luminal rigidity of the tubes. Importantly, all engineered tissues had similar or improved biomechanical properties compared to rat tracheas, which suggests they could be transplanted into a small animal model for airway defects. The modular, bottom up approach used to grow stem ...
Bioconjugate chemistry, Jan 23, 2015
Biomaterial properties such as mechanics, degradation rate and cell adhesivity affect cell behavi... more Biomaterial properties such as mechanics, degradation rate and cell adhesivity affect cell behaviors including spreading, proliferation and differentiation. To engineer complex tissues, it is often desirable to achieve precise spatial control over these properties. Here, methacrylated alginate (MA-ALG) was used to create hydrogels comprised of a single base material with regions of different types and levels of crosslinking and subsequently different material properties. Ionic and ultraviolet light crosslinking mechanisms were combined to create dual-crosslinked hydrogels with significantly increased stiffness and decreased swelling compared to calcium-crosslinked or UV-crosslinked hydrogels. MC3T3 cells showed significantly enhanced proliferation on the surface of dual-crosslinked hydrogels compared with calcium-crosslinked hydrogels. Photomasks were then used to create patterned hydrogels with precise spatial control over regions that were only calcium-crosslinked versus dual-cros...
Advanced drug delivery reviews, Jan 29, 2014
Limitations of current treatment options for critical size bone defects create a significant clin... more Limitations of current treatment options for critical size bone defects create a significant clinical need for tissue engineered bone strategies. This review describes how control over the spatiotemporal delivery of growth factors, nucleic acids, and drugs and small molecules may aid in recapitulating signals present in bone development and healing, regenerating interfaces of bone with other connective tissues, and enhancing vascularization of tissue engineered bone. State-of-the-art technologies used to create spatially controlled patterns of bioactive factors on the surfaces of materials, to build up 3D materials with patterns of signal presentation within their bulk, and to pattern bioactive factor delivery after scaffold fabrication are presented, highlighting their applications in bone tissue engineering. As these techniques improve in areas such as spatial resolution and speed of patterning, they will continue to grow in value as model systems for understanding cell responses ...
Stem cell research & therapy, 2014
Microcomputed tomography (microCT) has become a standard and essential tool for quantifying struc... more Microcomputed tomography (microCT) has become a standard and essential tool for quantifying structure-function relationships, disease progression, and regeneration in preclinical models and has facilitated numerous scientific and bioengineering advancements over the past 30 years. In this article, we recount the early events that led to the initial development of microCT and review microCT approaches for quantitative evaluation of bone, cartilage, and cardiovascular structures, with applications in fundamental structure-function analysis, disease, tissue engineering, and numerical modeling. Finally, we address several next-generation approaches under active investigation to improve spatial resolution, acquisition time, tissue contrast, radiation dose, and functional and molecular information.
ABSTRACT Biodegradability is a critical polymer scaffold characteristic for tissue engineering ap... more ABSTRACT Biodegradability is a critical polymer scaffold characteristic for tissue engineering applications. A scaffold for cell transplantation should provide mechanical support and structure in concert with the needs of newly developing tissue. Alginate hydrogels modified with specific adhesion ligands have previously been used to successfully engineer bone and cartilage tissue in vivo, but show negligible degradation in vitro and in viva. Gamma irradiating the alginate, which decreased the average molecular weight of the polymer chains, increased the rate of hydrogel degradation in viva and fibrous tissue ingrowth. Primary rat calvarial osteoblasts combined with gamma irradiated alginate modified with specific adhesion ligands significantly improved the rate, quality, and quantity of new bone tissue formed in vivo compared to the non-irradiated control condition. Control of both the degradation and adhesion characteristics of a polymer scaffold will be a powerful tool in regulating tissue regeneration processes.
Advanced Functional Materials, 2013
Advanced Healthcare Materials, 2015
Giving rise to both bone and cartilage during development, bone marrow-derived mesenchymal stem c... more Giving rise to both bone and cartilage during development, bone marrow-derived mesenchymal stem cells (hMSC) have the unique capacity to generate the complex tissues of the osteochondral interface. Utilizing a scaffold-free hMSC system, biphasic osteochondral constructs are incorporated with two types of growth factor-releasing microparticles to enable spatially organized differentiation. Gelatin microspheres (GM) releasing transforming growth factor-β1 (TGF-β1) combined with hMSC form the chondrogenic phase. The osteogenic phase contains hMSC only, mineral-coated hydroxyapatite microparticles (MCM), or MCM loaded with bone morphogenetic protein-2 (BMP-2), cultured in medium with or without BMP-2. After 4 weeks, TGF-β1 release from GM within the cartilage phase promotes formation of a glycosaminoglycan- and type II collagen-rich matrix, and has a local inhibitory effect on osteogenesis. In the osteogenic phase, type X collagen and osteopontin are produced in all conditions. However, calcification occurs on the outer edges of the chondrogenic phase in some constructs cultured in media containing BMP-2, and alkaline phosphatase levels are elevated, indicating that BMP-2 releasing MCM provides better control over region-specific differentiation. The production of complex, stem cell-derived osteochondral tissues via incorporated microparticles could enable earlier implantation, potentially improving outcomes in the treatment of osteochondral defects.
There issubstantial needforthereplacement oftissues inthecraniofacial complex duetocongenital def... more There issubstantial needforthereplacement oftissues inthecraniofacial complex duetocongenital defects, disease, andinjury. Thefield oftissue engineering, through theapplication ofengineering andbiological principles, hasthepotential tocre- atefunctional replacements fordamaged orpathologic tissues. Three mainapproaches totissue engineering havebeenpursued conduction, induction bybioactive factors, andcell transplantation. These approaches will bereviewed asthey havebeenapplied tokeytissues inthecraniofacial region. While manyobstacles muststill beovercome prior tothesuccessful clinical restoration of tissues suchasskeletal muscle andthesalivary glands, significant progress hasbeenachieved inthedevelopment ofseveral tissue equivalents, including skin, bone, andcartilage. Thecombined technologies ofgenetherapy anddrug delivery withcell transplan- tation will continue toincrease treatment options for craniofacial cosmetic andfunctional restoration.
Physical Review E, 2009
Aggregation in nondiffusion limited colloidal particle suspensions follows a temporal power-law d... more Aggregation in nondiffusion limited colloidal particle suspensions follows a temporal power-law dependence that is consistent with classical diffusion limited cluster aggregation models; however, the dynamic scaling exponents observed in these systems are not adequately described by diffusion limited cluster aggregation models, which expect these scaling exponents to be constant over all experimental conditions. We show here that the dynamic scaling
ISSCC. 2005 IEEE International Digest of Technical Papers. Solid-State Circuits Conference, 2005., 2005
Advanced healthcare materials, 2015
By silencing specific gene expression, short interfering RNA (siRNA) is a potent biomolecule for ... more By silencing specific gene expression, short interfering RNA (siRNA) is a potent biomolecule for regulating cell behavior in tissue engineering applications, and spatially patterning its presentation to cells may ultimately facilitate the engineering of complex tissues. The study by E. Alsberg and team on page 714 demonstrates a hydrogel system that presents a linear gradient of siRNA to encapsulated cells, inducing a spatial gradient of green fluorescent protein expression.
Biomaterials, 2015
There is a critical need to engineer a neotrachea because currently there are no long-term treatm... more There is a critical need to engineer a neotrachea because currently there are no long-term treatments for tracheal stenoses affecting large portions of the airway. In this work, a modular tracheal tissue replacement strategy was developed. High-cell density, scaffold-free human mesenchymal stem cell-derived cartilaginous rings and tubes were successfully generated through employment of custom designed culture wells and a ring-to-tube assembly system. Furthermore, incorporation of transforming growth factor-β1-delivering gelatin microspheres into the engineered tissues enhanced chondrogenesis with regard to tissue size and matrix production and distribution in the ring- and tube-shaped constructs, as well as luminal rigidity of the tubes. Importantly, all engineered tissues had similar or improved biomechanical properties compared to rat tracheas, which suggests they could be transplanted into a small animal model for airway defects. The modular, bottom up approach used to grow stem ...
Bioconjugate chemistry, Jan 23, 2015
Biomaterial properties such as mechanics, degradation rate and cell adhesivity affect cell behavi... more Biomaterial properties such as mechanics, degradation rate and cell adhesivity affect cell behaviors including spreading, proliferation and differentiation. To engineer complex tissues, it is often desirable to achieve precise spatial control over these properties. Here, methacrylated alginate (MA-ALG) was used to create hydrogels comprised of a single base material with regions of different types and levels of crosslinking and subsequently different material properties. Ionic and ultraviolet light crosslinking mechanisms were combined to create dual-crosslinked hydrogels with significantly increased stiffness and decreased swelling compared to calcium-crosslinked or UV-crosslinked hydrogels. MC3T3 cells showed significantly enhanced proliferation on the surface of dual-crosslinked hydrogels compared with calcium-crosslinked hydrogels. Photomasks were then used to create patterned hydrogels with precise spatial control over regions that were only calcium-crosslinked versus dual-cros...
Advanced drug delivery reviews, Jan 29, 2014
Limitations of current treatment options for critical size bone defects create a significant clin... more Limitations of current treatment options for critical size bone defects create a significant clinical need for tissue engineered bone strategies. This review describes how control over the spatiotemporal delivery of growth factors, nucleic acids, and drugs and small molecules may aid in recapitulating signals present in bone development and healing, regenerating interfaces of bone with other connective tissues, and enhancing vascularization of tissue engineered bone. State-of-the-art technologies used to create spatially controlled patterns of bioactive factors on the surfaces of materials, to build up 3D materials with patterns of signal presentation within their bulk, and to pattern bioactive factor delivery after scaffold fabrication are presented, highlighting their applications in bone tissue engineering. As these techniques improve in areas such as spatial resolution and speed of patterning, they will continue to grow in value as model systems for understanding cell responses ...
Stem cell research & therapy, 2014
Microcomputed tomography (microCT) has become a standard and essential tool for quantifying struc... more Microcomputed tomography (microCT) has become a standard and essential tool for quantifying structure-function relationships, disease progression, and regeneration in preclinical models and has facilitated numerous scientific and bioengineering advancements over the past 30 years. In this article, we recount the early events that led to the initial development of microCT and review microCT approaches for quantitative evaluation of bone, cartilage, and cardiovascular structures, with applications in fundamental structure-function analysis, disease, tissue engineering, and numerical modeling. Finally, we address several next-generation approaches under active investigation to improve spatial resolution, acquisition time, tissue contrast, radiation dose, and functional and molecular information.
ABSTRACT Biodegradability is a critical polymer scaffold characteristic for tissue engineering ap... more ABSTRACT Biodegradability is a critical polymer scaffold characteristic for tissue engineering applications. A scaffold for cell transplantation should provide mechanical support and structure in concert with the needs of newly developing tissue. Alginate hydrogels modified with specific adhesion ligands have previously been used to successfully engineer bone and cartilage tissue in vivo, but show negligible degradation in vitro and in viva. Gamma irradiating the alginate, which decreased the average molecular weight of the polymer chains, increased the rate of hydrogel degradation in viva and fibrous tissue ingrowth. Primary rat calvarial osteoblasts combined with gamma irradiated alginate modified with specific adhesion ligands significantly improved the rate, quality, and quantity of new bone tissue formed in vivo compared to the non-irradiated control condition. Control of both the degradation and adhesion characteristics of a polymer scaffold will be a powerful tool in regulating tissue regeneration processes.