Future Directions in Regenerative Medicine

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To date, regenerative medicine has led to new, FDA-approved therapies being used to treat a number of pathologies. Considerable research has enabled the fabrication of sophisticated grafts that exploit properties of scaffolding materials and cell manipulation technologies for controlling cell behavior and repairing tissue. These scaffolds can be molded to fit the patient's anatomy and be fabricated with substantial control over spatial positioning of cells.

Strategies are being developed to improve graft integration with the host vasculature and nervous system, particularly through controlled release of growth factors and vascular cell seeding, and the body's healing response can be elicited and augmented in a variety of ways, including immune system modulation.

New cell sources for transplantation that address the limited cell supply that hampered many past efforts are also being developed. A number of issues will be important for the advancement of regenerative medicine as a field. First, stem cells, whether isolated from adult tissue or induced, will often require tight control over their behavior to increase their safety profile and efficacy after transplantation. The creation of microenvironments, often modeled on various stem cell niches that provide specific cues, including morphogens and physical properties, or have the capacity to genetically manipulate target cells, will likely be key to promoting optimal regenerative responses from therapeutic cells.

Second, the creation of large engineered replacement tissues will require technologies that enable fully vascularized grafts to be anastomosed with host vessels at the time of transplant, allowing for graft survival. Thirdly, creating a proregeneration environment within the patient may dramatically improve outcomes of regenerative medicine strategies in general.

An improved understanding of the immune system's role in regeneration may aid this goal, as would technologies that promote a desirable immune response. A better understanding of how age, disease state, and the microbiome of the patient affect regeneration will likely also be important for advancing the field in many situations — Finally, 3D human tissue culture models of disease may allow testing of regenerative medicine approaches in human biology, as contrasted to the animal models currently used in preclinical studies.

Increased accuracy of disease models may improve the efficacy of regenerative medicine strategies and enhance the translation to the clinic of promising approaches The authors declare no conflict of interest. National Center for Biotechnology Information , U.

Published online Nov Mao a, b and David J. Mooney a, b, 1. Mao a John A. Mooney a John A. Author information Copyright and License information Disclaimer. Edited by Mark E.

This article has been cited by other articles in PMC. Abstract Organ and tissue loss through disease and injury motivate the development of therapies that can regenerate tissues and decrease reliance on transplantations. Therapies in the Market Since tissue engineering and regenerative medicine emerged as an industry about two decades ago, a number of therapies have received Food and Drug Administration FDA clearance or approval and are commercially available Table 1. Regenerative medicine FDA-approved products.

Open in a separate window. Therapies at the Preclinical Stage and in Clinical Testing A broad range of strategies at both the preclinical and clinical stages of investigation are currently being explored. Recapitulating Tissue and Organ Structure. Altering the Host Environment: Cell Infusions and Modulating the Immune System. Existing and New Cell Sources. Conclusion To date, regenerative medicine has led to new, FDA-approved therapies being used to treat a number of pathologies.

Footnotes The authors declare no conflict of interest. Tissue Eng Part B Rev. An FDA perspective on preclinical development of cell-based regenerative medicine products.

Regenerative medicine: Current therapies and future directions

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Therapies in the Market

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Tomei AA, et al. Device design and materials optimization of conformal coating for islets of Langerhans. Targeted delivery of progenitor cells for cartilage repair. Cheng Z, et al. Unfortunately classic options such as auto- and allografts have significant limitations and thus, alternative strategies should be used to reconstruct such large bone defects [1]. Another goal is to accelerate and enhance the quality of the bone repair in the shortest possible time [ 1 ]. In the last decade, tissue engineering and regenerative medicine TERM in its new concept by means of combination of tissue scaffolds, healing promotive factors and cells or stem cells have been introduced to orthopedic research and sports medicine [ 1 , 2 ].

Although several TERM based products have been introduced to the market in the recent years, none of them provided an acceptable solution with favorable outcome at long term follow-up [ 2 ]. Novel strategies using TERM based products are still under investigation. For designing a suitable bone substitute TERM based graft, some important characteristics have to be considered including, osteoconduction, osteoinduction, osteoincorporation, osteointegration and osteogenesis [ 2 ]. In addition, the graft should have biocompatibility and biodegradability [ 2 ].

To date, no TERM based graft having all the above mentioned characteristics has been designed, manufactured and its efficacy on bone healing and regeneration investigated. To design such a desirable graft, two points should be kept in mind including: To address these issues, the graft should be produced by using natural based polymers such as collagen, elastin, gelatin, hydroxyapatite, chitosan and three- or octa calcium phosphate [ 2 ]. These polymers provide optimum grades of biocompatibility and biodegradability. Unfortunately, most of the commercially available grafts are produced from synthetic polymers such as polyglycolic acid, polygalactin , and polydioxanone having low biodegradability and prolong the chronic inflammation which is not clinically pleasant [ 2 ].

Natural polymers have also an optimum osteoconductivity; the ability of a graft to guide tissue regeneration between bone edges [ 2 ]. However the biodegradability of the natural polymers is fast thus the implanted graft may not contributed in all parts of the healing process therefore, combining natural rapid absorbable as major part with synthetic low absorbable as minor part polymers, a hybrid scaffold can be produced with controllable absorbability [ 2 , 3 ].

Using natural polymers as major part of a graft also increases the osteoincorporative and osteointegrative properties of a TERM based graft because natural molecules have excellent bioactivity during bone repair [ 2 ]. The major challenge is the osteoinductivity of the TERM based grafts. In fact, there are few options for inducing bone mineralization and bone formation so that most of the TERM based grafts can only trigger osteoconduction with low effectiveness on osteoinduction.

In such cases, the new tissue fills the defect completely but has inferior mechanical property so that it would not be able to tolerate weight bearing forces due to the lack of mineralization [ 2 , 3 ]. The most investigated osteoinductive agent is a group of bone morphogenetic proteins BMPs , in which the type II is a popular type [ 3 ]. However, the BMPs have significant limitations and their high cost is their most important limitation [ 3 ].

Alternative osteoinductive agents are currently under investigation [ 4 - 8 ]. Platelet rich plasma and platelet gel are natural sources of growth factors and could contribute to bone induction however concerns are arising in their real efficacy on the healing process [ 2 , 4 ]. Recent studies have suggested that platelets may have only a modulatory role on inflammation and their growth factors may not be a major contributor during healing [ 4 ].

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