Ultrasound-responsive gene-activated matrices for osteogenic gene therapy using matrix-assisted sonoporation

Nomikou, Nikolitsa; Feichtinger, Georg A.; Saha, Subhas Chandra; Nuernberger, Sylvia; Heimel, Patrick; Redl, Heinz; McHale, Anthony P.

doi:10.1002/term.2406

Cited by 20 publications

(14 citation statements)

References 36 publications

(61 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A recent study applied ultrasound to intramuscularly implanted fibrin/ collagen hybrid matrices containing micro-bubbles, BMP-2 / 7 coexpression plasmids, and C2C12 cells in mice (48). Although that study combined exogenous cells within the scaffold, only a small amount of new bone was generated in vivo.…”

Section: Discussionmentioning

confidence: 99%

In situ bone tissue engineering via ultrasound-mediated gene delivery to endogenous progenitor cells in mini-pigs

et al. 2017

View full text Add to dashboard Cite

More than 2 million bone-grafting procedures are performed each year using autografts or allografts. However, both options carry disadvantages, and there remains a clear medical need for the development of new therapies for massive bone loss and fracture nonunions. We hypothesized that localized ultrasound-mediated, microbubble-enhanced therapeutic gene delivery to endogenous stem cells would induce efficient bone regeneration and fracture repair. To test this hypothesis, we surgically created a critical-sized bone fracture in the tibiae of Yucatán mini-pigs, a clinically relevant large animal model. A collagen scaffold was implanted in the fracture to facilitate recruitment of endogenous mesenchymal stem/progenitor cells (MSCs) into the fracture site. Two weeks later, transcutaneous ultrasound-mediated reporter gene delivery successfully transfected 40% of cells at the fracture site, and flow cytometry showed that 80% of the transfected cells expressed MSC markers. Human bone morphogenetic protein-6 (BMP-6) plasmid DNA was delivered using ultrasound in the same animal model, leading to transient expression and secretion of BMP-6 localized to the fracture area. Micro–computed tomography and biomechanical analyses showed that ultrasound-mediated BMP-6 gene delivery led to complete radiographic and functional fracture healing in all animals 6 weeks after treatment, whereas nonunion was evident in control animals. Collectively, these findings demonstrate that ultrasound-mediated gene delivery to endogenous mesenchy-mal progenitor cells can effectively treat nonhealing bone fractures in large animals, thereby addressing a major orthopedic unmet need and offering new possibilities for clinical translation.

show abstract

Section: Discussionmentioning

confidence: 99%

In situ bone tissue engineering via ultrasound-mediated gene delivery to endogenous progenitor cells in mini-pigs

et al. 2017

View full text Add to dashboard Cite

show abstract

“… 167 Such on-demand drug release could reduce side effects caused by excess drug dosing found in conventional administration. 168,169 – 170 Commonly used stimuli include pH, temperature, exposure to an electric or magnetic field, ultrasound, light irradiation, and biomolecules. These responsive systems involve “smart” responsive materials, so that the materials undergo considerable changes in response to the stimuli and thereby change the drug release kinetics (e.g.…”

Section: Biomimetic Strategies In Drug Deliverymentioning

confidence: 99%

Biomimetic delivery of signals for bone tissue engineering

et al. 2018

View full text Add to dashboard Cite

Bone tissue engineering is an exciting approach to directly repair bone defects or engineer bone tissue for transplantation. Biomaterials play a pivotal role in providing a template and extracellular environment to support regenerative cells and promote tissue regeneration. A variety of signaling cues have been identified to regulate cellular activity, tissue development, and the healing process. Numerous studies and trials have shown the promise of tissue engineering, but successful translations of bone tissue engineering research into clinical applications have been limited, due in part to a lack of optimal delivery systems for these signals. Biomedical engineers are therefore highly motivated to develop biomimetic drug delivery systems, which benefit from mimicking signaling molecule release or presentation by the native extracellular matrix during development or the natural healing process. Engineered biomimetic drug delivery systems aim to provide control over the location, timing, and release kinetics of the signal molecules according to the drug’s physiochemical properties and specific biological mechanisms. This article reviews biomimetic strategies in signaling delivery for bone tissue engineering, with a focus on delivery systems rather than specific molecules. Both fundamental considerations and specific design strategies are discussed with examples of recent research progress, demonstrating the significance and potential of biomimetic delivery systems for bone tissue engineering.

show abstract

“…An interesting novel method using matrix-assisted sonoporation was recently presented by Nomikou et al. 135 Their study employed a fibrin/collagen matrix containing microbubbles, BMP-2/7 coexpression plasmids and C2C12 cells. The construct was treated with ultrasound either in vitro or after implantation intramuscularly.…”

Section: Gene-activated Matrices (Gams)mentioning

confidence: 99%

“…An interesting novel method using matrix‐assisted sonoporation was recently presented by Nomikou et al . . Their study employed a fibrin/collagen matrix containing microbubbles, BMP‐2/7 co‐expression plasmids and C2C12 cells.…”

Section: In Vivo Gene Therapymentioning

confidence: 99%

Recent advances in gene‐enhanced bone tissue engineering

Betz

Kochanek

Rammelt

et al. 2018

The Journal of Gene Medicine

View full text Add to dashboard Cite

The loss of bone tissue represents a critical clinical condition that is frequently faced by surgeons. Substantial progress has been made in the area of bone research, providing insight into the biology of bone under physiological and pathological conditions, as well as tools for the stimulation of bone regeneration. The present review discusses recent advances in the field of gene-enhanced bone tissue engineering. Gene transfer strategies have emerged as highly effective tissue engineering approaches for supporting the repair of the musculoskeletal system. By contrast to treatment with recombinant proteins, genetically engineered cells can release growth factors at the site of injury over extended periods of time. Of particular interest are the expedited technologies that can be applied during a single surgical procedure in a cost-effective manner, allowing translation from bench to bedside. Several promising methods based on the intra-operative genetic manipulation of autologous cells or tissue fragments have been developed in preclinical studies. Moreover, gene therapy for bone regeneration has entered the clinical stage with clinical trials for the repair of alveolar bone. Current trends in gene-enhanced bone engineering are also discussed with respect to the movement of the field towards expedited, translational approaches. It is possible that gene-enhanced bone tissue engineering will become a clinical reality within the next few years.

show abstract

Ultrasound-responsive gene-activated matrices for osteogenic gene therapy using matrix-assisted sonoporation

Cited by 20 publications

References 36 publications

In situ bone tissue engineering via ultrasound-mediated gene delivery to endogenous progenitor cells in mini-pigs

In situ bone tissue engineering via ultrasound-mediated gene delivery to endogenous progenitor cells in mini-pigs

Biomimetic delivery of signals for bone tissue engineering

Recent advances in gene‐enhanced bone tissue engineering

Contact Info

Product

Resources

About