Born Again Bone: Tissue Engineering for Bone Repair

Braddock, Martin; Houston, Parul; Campbell, Callum J.; Ashcroft, G. W.

doi:10.1152/physiologyonline.2001.16.5.208

Cited by 66 publications

(67 citation statements)

References 17 publications

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“…where 1 x is the relative population density of osteoclasts (OCl), 2 x is the relative population density of osteoblasts (OBl), 3 x is the relative population density of osteocytes (OCt), 4 [10] and other well known Hill [26], Monod-Wyman-Changeux [29] and Koshland-Nemethy-Filmer [28].…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

“…Special emphasis should be paid to the potential to apply rapid manufacturing technology to generate bio-resorbable scaffolds for tissue engineering, which has been recognised for several years [2][3][4]. However, despite some promising results [5][6][7] the full potential of this approach can only be fully realised when the bone remodeling process is well understood.…”

Section: Introductionmentioning

confidence: 99%

“…In the second case study (2) was when all parameters were simultaneously and randomly varied. Because the number of parameters is quite large it was difficult to study regularly all combinations in the 13 dimensional parameter space.…”

mentioning

confidence: 99%

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Allosteric control model of bone remodelling containing periodical modes

Moroz¹,

Wimpenny²

2007

Biophysical Chemistry

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To help to understand the modelling process that occurs when a scaffold is implanted it is vital to understand the rather complex bone remodelling process prevalent in native bone.We have formulated a mathematical model that predicts osteoactivity both in scaffolds, as well as in bone in vivo and could set a basis for the more detailed allosteric models. The model is extended towards a bio-cybernetic vision of basic multicellular unit (BMU) action, when some of the regulation loops have been modified to reflect the allosteric control mechanisms, developed by Michaels-Menten, Hill, Koshland-Nemethy-Filmer, Monod-Wyman-Changeux.By implementation of this approach a four-dimensional system was obtained that shows steady cyclic behaviour using a wide range of constants with clear biological meaning. We have observed that a local steady-state appears as a limiting cycle in multidimensional phase space and this is discussed in this paper. Physiological interpretation of this limiting four-dimension cycle possibly related to a conservative-like value has been proposed. Analysis and simulation of the model has shown an analogy between this conservative value, as a kind of substrateenergy regenerative potential of the bone remodelling system with a molecular nature, and to the classical physical value -energy. This dynamic recovery potential is directed against both mechanical and biomechanical damage to the bone. Furthermore, the current model has credibility when compared to the normal bone remodelling process. In the framework of widely recognised Hill mechanisms of allosteric regulation the cyclic attractor, described formerly for a pure cellular model, prevails for different forms of feedback control. This result indicates the viability of the proposed existence of a conservative value (analogous to energy) that characterises the recovery potential of the bone remodelling cycle. Linear stability analysis has been performed in order to determine the robustness of the basic state, however, additional work is required to study a wider range of constants.

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Section: Accepted M Manuscriptmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Allosteric control model of bone remodelling containing periodical modes

Moroz¹,

Wimpenny²

2007

Biophysical Chemistry

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“…One possible option to help stabilizing fractures with a poor healing prognosis is the use of external fi xation devices, although these often result in the production of unstable bone with a high probability of re-fracture (Braddock et al, 2001). For the treatment of extended bone defects following trauma, cancer resection or non-union fractures, more sophisticated treatments than the standard conservative or surgical therapies may be required.…”

Section: Introductionmentioning

confidence: 99%

“…Allografts from cadavers or living donors may also be used; these are usually sourced from a bone bank. Although bone grafting is generally successful, the limited amount of available donor tissue and the high associated morbidity, resulting in numbness or tingling at the donor site, infection or prolonged pain make the need for development of alternative therapies evident (Braddock et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Osteogenic molecules for clinical applications: improving the BMP-collagen system

et al. 2013

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Among the osteogenic growth factors used for bone tissue engineering, bone morphogenetic proteins (BMPs) are the most extensively studied for use in orthopaedic surgery. BMP-2 and BMP-7 have been widely investigated for developing therapeutic strategies and are the only two approved for use in several clinical applications. Due to the chemical and biological characteristics of these molecules, their authorised uses are always in combination with a carrier based on collagen type I. Although the use of these growth factors is considered safe in the short term, the very high doses needed to obtain signifi cant osteoinduction make these treatments expensive and their longterm safety uncertain, since they are highly pleiotropic and have the capacity to induce ectopic ossifi cation in the surrounding tissues. Therefore it is necessary to improve the currently used BMP-collagen system in terms of effi ciency, biosecurity and costs. There are several strategies to increase the clinical eff ectiveness of these treatments. In this review we summarize the most promising results and our related work focused on this fi eld through two diff erent approaches: i) the development of recombinant BMPs with additional features, and ii) complementing these systems with other growth factors or molecules to enhance or accelerate osteogenesis.

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Design, fabrication, and characterization of a multimodal reconfigurable bioreactor for bone tissue engineering

Montorsi

Genchi

Pasquale

et al. 2022

Biotech & Bioengineering

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In the past decades, bone tissue engineering developed and exploited many typologies of bioreactors, which, besides providing proper culture conditions, aimed at integrating those bio‐physical stimulations that cells experience in vivo, to promote osteogenic differentiation. Nevertheless, the highly challenging combination and deployment of many stimulation systems into a single bioreactor led to the generation of several unimodal bioreactors, investigating one or at mostly two of the required biophysical stimuli. These systems miss the physiological mimicry of bone cells environment, and often produced contrasting results, thus making the knowledge of bone mechanotransduction fragmented and often inconsistent. To overcome this issue, in this study we developed a perfusion and electroactive‐vibrational reconfigurable stimulation bioreactor to investigate the differentiation of SaOS‐2 bone‐derived cells, hosting a piezoelectric nanocomposite membrane as cell culture substrate. This multimodal perfusion bioreactor is designed based on a numerical (finite element) model aimed at assessing the possibility to induce membrane nano‐scaled vibrations (with ~12 nm amplitude at a frequency of 939 kHz) during perfusion (featuring 1.46 dyn cm−2 wall shear stress), large enough for inducing a physiologically‐relevant electric output (in the order of 10 mV on average) on the membrane surface. This study explored the effects of different stimuli individually, enabling to switch on one stimulation at a time, and then to combine them to induce a faster bone matrix deposition rate. Biological results demonstrate that the multimodal configuration is the most effective in inducing SaOS‐2 cell differentiation, leading to 20‐fold higher collagen deposition compared to static cultures, and to 1.6‐ and 1.2‐fold higher deposition than the perfused‐ or vibrated‐only cultures. These promising results can provide tissue engineering scientists with a comprehensive and biomimetic stimulation platform for a better understanding of mechanotransduction phenomena beyond cells differentiation.

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Born Again Bone: Tissue Engineering for Bone Repair

Cited by 66 publications

References 17 publications

Allosteric control model of bone remodelling containing periodical modes

Allosteric control model of bone remodelling containing periodical modes

Osteogenic molecules for clinical applications: improving the BMP-collagen system

Design, fabrication, and characterization of a multimodal reconfigurable bioreactor for bone tissue engineering

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