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Synthetic bone mimetic matrix-mediated in situ bone tissue formation through host cell recruitment.

ABSTRACT: Advances in tissue engineering have offered new opportunities to restore anatomically and functionally compromised tissues. Although traditional tissue engineering approaches that utilize biomaterials and cells to create tissue constructs for implantation or biomaterials as a scaffold to deliver cells are promising, strategies that can activate endogenous cells to promote tissue repair are more clinically attractive. Here, we demonstrate that an engineered injectable matrix mimicking a calcium phosphate (CaP)-rich bone-specific microenvironment can recruit endogenous cells to form bone tissues in vivo. Comparison of matrix alone with that of bone marrow-soaked or bFGF-soaked matrix demonstrates similar extent of neo-bone formation and bridging of decorticated transverse processes in a posterolateral lumbar fusion rat model. Synthetic biomaterials that stimulate endogenous cells without the need for biologics to assist tissue repair could circumvent limitations associated with conventional tissue engineering approaches, including ex vivo cell processing and laborious efforts, thereby accelerating the translational aspects of regenerative medicine.

SUBMITTER: Shih YR

PROVIDER: S-EPMC5644488 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Synthetic bone mimetic matrix-mediated in situ bone tissue formation through host cell recruitment.

Shih Yu-Ru YR Phadke Ameya A Yamaguchi Tomonori T Kang Heemin H Inoue Nozomu N Masuda Koichi K Varghese Shyni S

Acta biomaterialia 20150321

Advances in tissue engineering have offered new opportunities to restore anatomically and functionally compromised tissues. Although traditional tissue engineering approaches that utilize biomaterials and cells to create tissue constructs for implantation or biomaterials as a scaffold to deliver cells are promising, strategies that can activate endogenous cells to promote tissue repair are more clinically attractive. Here, we demonstrate that an engineered injectable matrix mimicking a calcium p ...[more]

PMID: 25805106

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Project description:Emerging studies show the potential application of synthetic biomaterials that are intrinsically osteoconductive and osteoinductive as bone grafts to treat critical bone defects. Here, the biomaterial not only assists recruitment of endogenous cells, but also supports cellular activities relevant to bone tissue formation and function. While such biomaterial-mediated in situ tissue engineering is highly attractive, success of such an approach relies largely on the regenerative potential of the recruited cells, which is anticipated to vary with age. In this study, we investigated the effect of the age of the host on mineralized biomaterial-mediated bone tissue repair using critical-sized cranial defects as a model system. Mice of varying ages, 1-month-old (juvenile), 2-month-old (young-adult), 6-month-old (middle-aged), and 14-month-old (elderly), were used as recipients. Our results show that the bio-mineralized scaffolds support bone tissue formation by recruiting endogenous cells for all groups albeit with differences in an age-related manner. Analyses of bone tissue formation after 2 and 8?weeks post-treatment show low mineral deposition and reduced number of osteocalcin and tartrate-resistant acid phosphatase (TRAP)-expressing cells in elderly mice. STATEMENT OF SIGNIFICANCE:Tissue engineering strategies that promote tissue repair through recruitment of endogenous cells will have a significant impact in regenerative medicine. Previous studies from our group have shown that biomineralized materials containing calcium phosphate minerals can contribute to neo-bone tissue through recruitment and activation of endogenous cells. In this study, we investigated the effect of age of the recipient on biomaterial-mediated bone tissue repair. Our results show that the age of the recipient mouse had a significant impact on the quality and quantity of the engineered neo-bone tissues, in which delayed/compromised bone tissue formation was observed in older mice. These findings are in agreement with the clinical observations that age of patients is a key factor in bone repair.

Project description:Despite serving as the clinical "gold standard" treatment for critical size bone defects, decellularized allografts suffer from long-term failure rates of ~60% due to the absence of the periosteum. Stem and osteoprogenitor cells within the periosteum orchestrate autograft healing through host cell recruitment, which initiates the regenerative process. To emulate periosteum-mediated healing, tissue engineering approaches have been utilized with mixed outcomes. While vascularization has been widely established as critical for bone regeneration, innervation was recently identified to be spatiotemporally regulated together with vascularization and similarly indispensable to bone healing. Notwithstanding, there are no known approaches that have focused on periosteal matrix cues to coordinate host vessel and/or axon recruitment. Here, we investigated the influence of hydrogel degradation mechanism, i.e. hydrolytic or enzymatic (cell-dictated), on tissue engineered periosteum (TEP)-modified allograft healing, especially host vessel/nerve recruitment and integration. Matrix metalloproteinase (MMP)-degradable hydrogels supported endothelial cell migration from encapsulated spheroids whereas no migration was observed in hydrolytically degradable hydrogels in vitro, which correlated with increased neurovascularization in vivo. Specifically, ~2.45 and 1.84-fold, and ~3.48 and 2.58-fold greater vessel and nerve densities with high levels of vessel and nerve co-localization was observed using MMP degradable TEP (MMP-TEP) -modified allografts versus unmodified and hydrolytically degradable TEP (Hydro-TEP)-modified allografts, respectively, at 3 weeks post-surgery. MMP-TEP-modified allografts exhibited greater longitudinal graft-localized vascularization and endochondral ossification, along with 4-fold and 2-fold greater maximum torques versus unmodified and Hydro-TEP-modified allografts after 9 weeks, respectively, which was comparable to that of autografts. In summary, our results demonstrated that the MMP-TEP coordinated allograft healing via early stage recruitment and support of host neurovasculature.

Dataset Information

Synthetic bone mimetic matrix-mediated in situ bone tissue formation through host cell recruitment.

Publications

Synthetic bone mimetic matrix-mediated in situ bone tissue formation through host cell recruitment.

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