The scope and sequence of growth factor delivery for vascularized bone tissue regeneration

Tissue engineering is a promising alternative to autografts or allografts for the regeneration of large bone defects. Cell-free biomaterials with different degrees of sophistication can be used for several therapeutic indications, to stimulate bone repair by the host tissue. However, when osteoprogenitors are not available in the damaged tissue, exogenous cells with an osteoblast differentiation potential must be provided. These cells should have the capacity to colonize the defect and to participate in the building of new bone tissue. To achieve this goal, cells must survive, remain in the defect site, eventually proliferate, and differentiate into mature osteoblasts. A critical issue for these engrafted cells is to be fed by oxygen and nutrients: the transient absence of a vascular network upon implantation is a major challenge for cells to survive in the site of implantation, and different strategies can be followed to promote cell survival under poor oxygen and nutrient supply and to promote rapid vascularization of the defect area. These strategies involve the use of scaffolds designed to create the appropriate micro-environment for cells to survive, proliferate, and differentiate in vitro and in vivo. Hydrogels are an eclectic class of materials that can be easily cellularized and provide effective, minimally invasive approaches to fill bone defects and favor bone tissue regeneration. Furthermore, by playing on their composition and processing, it is possible to obtain biocompatible systems with adequate chemical, biological, and mechanical properties. However, only a good combination of scaffold and cells, possibly with the aid of incorporated growth factors, can lead to successful results in bone regeneration. This review presents the strategies used to design cellularized hydrogel-based systems for bone regeneration, identifying the key parameters of the many different micro-environments created within hydrogels.

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“…autografts) or the scaffold material and their proliferation to create a cellular environment prone to osteogenesis. 35 …”

Section: Hydrogels: Suitable Micro-environments For Btementioning

confidence: 99%

Cellularizing hydrogel-based scaffolds to repair bone tissue: How to create a physiologically relevant micro-environment?

et al. 2017

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“…Mechanical competence of the material is also important to provide an osteoconductive scaffold. This review will look at different approaches that have been studied in an attempt to improve the mechanical performance of hydrogel scaffolds.Osteogenicity is the property of those scaffolds that contain osteoprogenitor cells and favour their adhesion and proliferation [36]. This review will look at the different types of stem cells that can be used in bone regeneration and strategies for their inclusion in hydrogel scaffolds.…”

Section: Bone Tissue Engineeringmentioning

confidence: 99%

“…Osteogenicity is the property of those scaffolds that contain osteoprogenitor cells and favour their adhesion and proliferation [36]. This review will look at the different types of stem cells that can be used in bone regeneration and strategies for their inclusion in hydrogel scaffolds.…”

Section: Bone Tissue Engineeringmentioning

confidence: 99%

“…Thus, developing new strategies for the formulation and delivery of these growth factors could address the unmet clinical need for safe use of bone inducing biomaterials. Furthermore, research has demonstrated that physiological bone healing involves several different factors released at different times (Figure 1), indicating that release of a single growth factor would be an oversimplification in an attempt to mimic the physiological response [36]. …”

Section: Hydrogels As Scaffolds and Delivery Platformsmentioning

confidence: 99%

“…The strategies for sustained release are very similar; in general, a biodegradable or bioerodible multiparticulate system is introduced in the gel to further delay the release of the entrapped macromolecule. Strategies such as core-shell and layer-by-layer deposition are commonly used for the encapsulation of one or more growth factors [36]. …”

Section: Hydrogels As Scaffolds and Delivery Platformsmentioning

confidence: 99%

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Composite Hydrogels for Bone Regeneration

et al. 2016

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Over the past few decades, bone related disorders have constantly increased. Among all pathological conditions, osteoporosis is one of the most common and often leads to bone fractures. This is a massive burden and it affects an estimated 3 million people only in the UK. Furthermore, as the population ages, numbers are due to increase. In this context, novel biomaterials for bone fracture regeneration are constantly under development. Typically, these materials aim at favoring optimal bone integration in the scaffold, up to complete bone regeneration; this approach to regenerative medicine is also known as tissue engineering (TE). Hydrogels are among the most promising biomaterials in TE applications: they are very flexible materials that allow a number of different properties to be targeted for different applications, through appropriate chemical modifications. The present review will focus on the strategies that have been developed for formulating hydrogels with ideal properties for bone regeneration applications. In particular, aspects related to the improvement of hydrogels’ mechanical competence, controlled delivery of drugs and growth factors are treated in detail. It is hoped that this review can provide an exhaustive compendium of the main aspects in hydrogel related research and, therefore, stimulate future biomaterial development and applications.

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Gelatin Nanoparticle‐Injectable Platelet‐Rich Fibrin Double Network Hydrogels with Local Adaptability and Bioactivity for Enhanced Osteogenesis

Chen

Yuan

et al. 2020

Adv Healthcare Materials

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Bone healing is a dynamic process regulated by biochemical signals such as chemokines and growth factors, and biophysical signals such as topographical and mechanical features of extracellular matrix or mechanical stimuli. Hereby, a mechanically tough and bioactive hydrogel based on autologous injectable platelet‐rich fibrin (iPRF) modified with gelatin nanoparticles (GNPs) is developed. This composite hydrogel demonstrates a double network (DN) mechanism, wherein covalent network of fibrin serves to maintain material integrity, and self‐assembled colloidal network of GNPs dissipates force upon loading. A rabbit sinus augmentation model is used to investigate the bioactivity and osteogenesis capacity of the DN hydrogels. The DN hydrogels adapt to the local environmental complexity of bone defects, i.e., accommodate the irregular shape of the defects and withstand the pressure formed in the maxillary sinus during animal's respiration process. The DN hydrogel is also demonstrated to absorb and prolong the release of the bioactive growth factors stemming from iPRF, which could have contributed to the early angiogenesis and osteogenesis observed inside the sinus. This adaptable and bioactive DN hydrogel can achieve enhanced bone regeneration in treating complex bone defects by maintaining long‐term bone mass and withstanding the functional mechanical stimuli.

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The scope and sequence of growth factor delivery for vascularized bone tissue regeneration

Cited by 64 publications

References 123 publications

Cellularizing hydrogel-based scaffolds to repair bone tissue: How to create a physiologically relevant micro-environment?

Cellularizing hydrogel-based scaffolds to repair bone tissue: How to create a physiologically relevant micro-environment?

Composite Hydrogels for Bone Regeneration

Gelatin Nanoparticle‐Injectable Platelet‐Rich Fibrin Double Network Hydrogels with Local Adaptability and Bioactivity for Enhanced Osteogenesis

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