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Journal ArticleDOI

Bone regenerative medicine: classic options, novel strategies, and future directions

TL;DR: Tissue engineering is a new and developing option that had been introduced to reduce limitations of bone grafts and improve the healing processes of the bone fractures and defects and may open new insights in the near future.
Abstract: This review analyzes the literature of bone grafts and introduces tissue engineering as a strategy in this field of orthopedic surgery. We evaluated articles concerning bone grafts; analyzed characteristics, advantages, and limitations of the grafts; and provided explanations about bone-tissue engineering technologies. Many bone grafting materials are available to enhance bone healing and regeneration, from bone autografts to graft substitutes; they can be used alone or in combination. Autografts are the gold standard for this purpose, since they provide osteogenic cells, osteoinductive growth factors, and an osteoconductive scaffold, all essential for new bone growth. Autografts carry the limitations of morbidity at the harvesting site and limited availability. Allografts and xenografts carry the risk of disease transmission and rejection. Tissue engineering is a new and developing option that had been introduced to reduce limitations of bone grafts and improve the healing processes of the bone fractures and defects. The combined use of scaffolds, healing promoting factors, together with gene therapy, and, more recently, three-dimensional printing of tissue-engineered constructs may open new insights in the near future.

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Citations
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Journal ArticleDOI
TL;DR: Developments in fabricating sophisticated grafts and tissue mimics and technologies for integrating grafts with host vasculature will be discussed, and directions for current and future regenerative medicine therapies are proposed.
Abstract: Organ and tissue loss through disease and injury motivate the development of therapies that can regenerate tissues and decrease reliance on transplantations. Regenerative medicine, an interdisciplinary field that applies engineering and life science principles to promote regeneration, can potentially restore diseased and injured tissues and whole organs. Since the inception of the field several decades ago, a number of regenerative medicine therapies, including those designed for wound healing and orthopedics applications, have received Food and Drug Administration (FDA) approval and are now commercially available. These therapies and other regenerative medicine approaches currently being studied in preclinical and clinical settings will be covered in this review. Specifically, developments in fabricating sophisticated grafts and tissue mimics and technologies for integrating grafts with host vasculature will be discussed. Enhancing the intrinsic regenerative capacity of the host by altering its environment, whether with cell injections or immune modulation, will be addressed, as well as methods for exploiting recently developed cell sources. Finally, we propose directions for current and future regenerative medicine therapies.

592 citations

Journal ArticleDOI
TL;DR: This review highlights the current research in bone biofabrication, the necessary factors for success, in addition to the current limitations affecting biofabricsation, some of which are a consequence of the limitations of the additive manufacturing technology itself.

459 citations


Cites background from "Bone regenerative medicine: classic..."

  • ...As such, there is an increasing need for new treatments for patients with musculoskeletal diseases as evidenced by bone being the next most transplanted tissue after blood [1, 2]....

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  • ...Previous reviews have comprehensively listed the most common combinations of these biomaterials, with and without cells seeded, that have been investigated using in vitro or in vivo methods for their potential use in bone tissue engineering [2, 40, 96, 99-103]....

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Journal ArticleDOI
TL;DR: This review will focus on the applications of various cutting-edge bioactive hydrogels systems in bone regeneration, as well as their advantages and limitations, and classify recently developed polymeric materials for hydrogel synthesis.

325 citations

Journal ArticleDOI
TL;DR: This review focuses on the relationship between the porosity and pore size of scaffolds and subsequent osteogenesis, vascularisation and scaffold degradation during bone regeneration.

303 citations

Journal ArticleDOI
TL;DR: Hyperelastic “bone” did not elicit a negative immune response, became vascularized, quickly integrated with surrounding tissues, and rapidly ossified and supported new bone growth without the need for added biological factors, set it apart from many of the materials now available for bone repair.
Abstract: Despite substantial attention given to the development of osteoregenerative biomaterials, severe deficiencies remain in current products. These limitations include an inability to adequately, rapidly, and reproducibly regenerate new bone; high costs and limited manufacturing capacity; and lack of surgical ease of handling. To address these shortcomings, we generated a new, synthetic osteoregenerative biomaterial, hyperelastic “bone” (HB). HB, which is composed of 90 weight % (wt %) hydroxyapatite and 10 wt % polycaprolactone or poly(lactic- co -glycolic acid), could be rapidly three-dimensionally (3D) printed (up to 275 cm 3 /hour) from room temperature extruded liquid inks. The resulting 3D-printed HB exhibited elastic mechanical properties (~32 to 67% strain to failure, ~4 to 11 MPa elastic modulus), was highly absorbent (50% material porosity), supported cell viability and proliferation, and induced osteogenic differentiation of bone marrow–derived human mesenchymal stem cells cultured in vitro over 4 weeks without any osteo-inducing factors in the medium. We evaluated HB in vivo in a mouse subcutaneous implant model for material biocompatibility (7 and 35 days), in a rat posterolateral spinal fusion model for new bone formation (8 weeks), and in a large, non-human primate calvarial defect case study (4 weeks). HB did not elicit a negative immune response, became vascularized, quickly integrated with surrounding tissues, and rapidly ossified and supported new bone growth without the need for added biological factors.

287 citations

References
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Journal ArticleDOI
TL;DR: Among women with low bone mass and existing vertebral fractures, alendronate is well tolerated and substantially reduces the frequency of morphometric and clinical vertebra fractures, as well as other clinical fractures.

3,730 citations

Journal ArticleDOI
TL;DR: The integration of CTD with SFF to build designer tissue-engineering scaffolds is reviewed and the mechanical properties and tissue regeneration achieved using designer scaffolds are details.
Abstract: A paradigm shift is taking place in medicine from using synthetic implants and tissue grafts to a tissue engineering approach that uses degradable porous material scaffolds integrated with biological cells or molecules to regenerate tissues. This new paradigm requires scaffolds that balance temporary mechanical function with mass transport to aid biological delivery and tissue regeneration. Little is known quantitatively about this balance as early scaffolds were not fabricated with precise porous architecture. Recent advances in both computational topology design (CTD) and solid free-form fabrication (SFF) have made it possible to create scaffolds with controlled architecture. This paper reviews the integration of CTD with SFF to build designer tissue-engineering scaffolds. It also details the mechanical properties and tissue regeneration achieved using designer scaffolds. Finally, future directions are suggested for using designer scaffolds with in vivo experimentation to optimize tissue-engineering treatments, and coupling designer scaffolds with cell printing to create designer material/biofactor hybrids.

3,487 citations

Journal ArticleDOI
TL;DR: In this article, the crystal and molecular structure of cellulose Iβ were determined using synchrotron and neutron diffraction data recorded from oriented fibrous samples prepared by aligning cellulose microcrystals from tunicin.
Abstract: The crystal and molecular structure together with the hydrogen-bonding system in cellulose Iβ has been determined using synchrotron and neutron diffraction data recorded from oriented fibrous samples prepared by aligning cellulose microcrystals from tunicin. These samples diffracted both synchrotron X-rays and neutrons to better than 1 A resolution (>300 unique reflections; P21). The X-ray data were used to determine the C and O atom positions. The resulting structure consisted of two parallel chains having slightly different conformations and organized in sheets packed in a “parallel-up” fashion, with all hydroxymethyl groups adopting the tg conformation. The positions of hydrogen atoms involved in hydrogen-bonding were determined from a Fourier-difference analysis using neutron diffraction data collected from hydrogenated and deuterated samples. The hydrogen atoms involved in the intramolecular O3···O5 hydrogen bonds have well-defined positions, whereas those corresponding to O2 and O6 covered a wider v...

2,583 citations


"Bone regenerative medicine: classic..." refers background in this paper

  • ...Cellulose is the most abundant organic polymer on Earth [89]....

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Journal ArticleDOI
TL;DR: The present review outlines the major new findings on the pharmaceutical applications of chitosan-based micro/nanoparticulate drug delivery systems published over the past decade and discusses critically the usefulness of these systems in delivering the bioactive molecules.

2,314 citations

Journal ArticleDOI
TL;DR: In this paper, the authors reviewed biomedical applications of collagen including the collagen film, which was developed as a matrix system for evaluation of tissue calcification and for the embedding of a single cell suspension for tumorigenic study.

1,758 citations


"Bone regenerative medicine: classic..." refers background in this paper

  • ...To produce a scaffold, the biologic tissues should be degraded to their components and then redesigned according to the tissue engineering goals [67,68]....

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  • ..., collagen + hydroxyapatite, collagen + chitosan) and therefore have low antigenicity compared with cadaveric grafts [66,67]....

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