The Role of Gene Therapy in Regenerative Surgery
Background: In the past two decades, regenerative surgeons have focused increasing attention on the potential of gene therapy for treatment of local disorders and injuries. Gene transfer techniques may provide an effective local and short-term induction of growth factors without the limits of other topical therapies. In 2002, Tepper and Mehrara accurately reviewed the topic: given the substantial advancement of research on this issue, an updated review is provided. Methods: Literature indexed in the National Center for Biotechnology Information database (PubMed) has been reviewed using variable combinations of keywords ("gene therapy," "regenerative medicine," "tissue regeneration," and "gene medicine"). Articles investigating the association between gene therapies and local pathologic conditions have been considered. Attention has been focused on articles published after 2002. Further literature has been obtained by analysis of references listed in reviewed articles. Results: Gene therapy approaches have been successfully adopted in preclinical models for treatment of a large variety of local diseases affecting almost every type of tissue. Experiences in abnormalities involving skin (e.g., chronic wounds, burn injuries, pathologic scars), bone, cartilage, endothelia, and nerves have been reviewed. In addition, the supporting role of gene therapies to other tissue-engineering approaches has been discussed. Despite initial reports, clinical evidence has been provided only for treatment of diabetic ulcers, rheumatoid arthritis, and osteoarthritis. Conclusions: Translation of gene therapy strategies into human clinical trials is still a lengthy, difficult, and expensive process. Even so, cutting-edge gene therapy-based strategies in reconstructive procedures could soon set valuable milestones for development of efficient treatments in a growing number of local diseases and injuries.
[Show abstract] [Hide abstract] ABSTRACT: The exstrophy–epispadias complex is a rare spectrum of anomalies affecting the genitourinary system, anterior abdominal wall, and pelvis. Recent advances in the repair of classic bladder exstrophy (CBE) and cloacal exstrophy (CE) have resulted in significant changes in outcomes of surgical management (including higher continence rate, fewer surgical complications, and better cosmesis) and health-related quality of life in these patients. These noteworthy changes resulted from advances in the pathophysiological and genetic backgrounds of this disease and better radiologic assessment of the three-dimensional anatomy of the bony pelvis and its musculature. A PubMed search was performed with the keyword exstrophy. The resulting literature pertaining to genetics, stem cells, imaging, tissue engineering, epidemiology, and endocrinology was reviewed. The following represents an overview of the advances in basic science understanding and imaging of the exstrophy–epispadias spectrum and discusses their possible and future effects on the management of CBE and CE.0Comments 2Citations
- "If a precise genetic signature is found, it may be possible in the future to manipulate them via small molecules, interference RNA, or other " gene therapies " . Combining such approaches with tissue-engineering technologies may allow for further treatment options, and thus indicate the need for future experimental studies . Finding genes associated with desmosome structures and functions and cytoskeletal assembly may eventually allow for " re-engineering " of the diseased tissue of the bladder into healthy tissues by targeting the underexpressed genes and inhibiting overexpressed genes. "
- [Show abstract] [Hide abstract] ABSTRACT: Anisotropic geometries are critical for eliciting cell alignment to dictate tissue microarchitectures and biological functions. Current fabrication techniques are complex and utilize toxic solvents, hampering their applications for translational research. Here, we present a novel simple, solvent-free and reproducible method via uniaxial stretching for incorporating anisotropic topographies on bioresorbable films with ambitions to realize stem cell alignment control. Uniaxial stretching of poly(ε-caprolactone) (PCL) films resulted in a 3D micro-ridge/groove topography (inter-ridge-distance: ~6 μm, ridge-length: ~90 μm, ridge-depth: 200-900 nm) with uniform distribution and controllable orientation by the direction of stretch on the whole film surface. Increasing stretch temperature (Ts) and draw ratio (DR), the inter-ridge-distance was reduced and ridge-length increased. Through modification of hydrolysis, increased surface hydrophilicity was achieved, while maintaining the morphology of PCL ridge/grooves. Upon seeding human mesenchymal stem cells (hMSCs) on uniaxial-stretched PCL films (UX-PCL), aligned hMSC organization was obtained. Compared to un-stretched films, hMSCs on UX-PCL had larger increase in cellular alignment (>85%) and elongation, without indication of cytotoxicity or reduction in cellular proliferation. This aligned hMSC organization was homogenous and stable-maintained with controlled orientation along the ridges on the whole UX-PCL surface for over two weeks. Moreover, the hMSCs on UX-PCL had a higher level of myogenic genes' expression than that on the un-stretched films. We conclude that uniaxial stretching has potential in patterning film topography with anisotropic structures. The UX-PCL in conjunction with hMSCs could be used as "basic units" to create tissue constructs with microscale control of cellular alignment and elongation for tissue engineering (T.E.) applications.0Comments 17Citations
- [Show abstract] [Hide abstract] ABSTRACT: Polymeric nanofibers have potential as tissue engineering scaffolds, as they mimic the nanoscale properties and structural characteristics of native extracellular matrix (ECM). Nanofibers composed of natural and synthetic polymers, biomimetic composites, ceramics, and metals have been fabricated by electrospinning for various tissue engineering applications. The inherent advantages of electrospinning nanofibers include the generation of substrata with high surface area-to-volume ratios, the capacity to precisely control material and mechanical properties, and a tendency for cellular in-growth due to interconnectivity within the pores. Furthermore, the electrospinning process affords the opportunity to engineer scaffolds with micro to nanoscale topography similar to the natural ECM. This review describes the fundamental aspects of the electrospinning process when applied to spinnable natural and synthetic polymers; particularly those parameters that influence fiber geometry, morphology, mesh porosity, and scaffold mechanical properties. We describe cellular responses to fiber morphology achieved by varying processing parameters and highlight successful applications of electrospun nanofibrous scaffolds when used to tissue engineer bone, skin, and vascular grafts.0Comments 25Citations