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Concise Review: Biomimetic Functionalization of Biomaterials to Stimulate the Endogenous Healing Process of Cartilage and Bone Tissue.

ABSTRACT: Musculoskeletal reconstruction is an ongoing challenge for surgeons as it is required for one out of five patients undergoing surgery. In the past three decades, through the close collaboration between clinicians and basic scientists, several regenerative strategies have been proposed. These have emerged from interdisciplinary approaches that bridge tissue engineering with material science, physiology, and cell biology. The paradigm behind tissue engineering is to achieve regeneration and functional recovery using stem cells, bioactive molecules, or supporting materials. Although plenty of preclinical solutions for bone and cartilage have been presented, only a few platforms have been able to move from the bench to the bedside. In this review, we highlight the limitations of musculoskeletal regeneration and summarize the most relevant acellular tissue engineering approaches. We focus on the strategies that could be most effectively translate in clinical practice and reflect on contemporary and cutting-edge regenerative strategies in surgery. Stem Cells Translational Medicine 2017;6:2186-2196.

SUBMITTER: Taraballi F

PROVIDER: S-EPMC5702525 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Concise Review: Biomimetic Functionalization of Biomaterials to Stimulate the Endogenous Healing Process of Cartilage and Bone Tissue.

Taraballi Francesca F Bauza Guillermo G McCulloch Patrick P Harris Josh J Tasciotti Ennio E

Stem cells translational medicine 20171028 12

Musculoskeletal reconstruction is an ongoing challenge for surgeons as it is required for one out of five patients undergoing surgery. In the past three decades, through the close collaboration between clinicians and basic scientists, several regenerative strategies have been proposed. These have emerged from interdisciplinary approaches that bridge tissue engineering with material science, physiology, and cell biology. The paradigm behind tissue engineering is to achieve regeneration and functi ...[more]

PMID: 29080279

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Project description:Bone is a unique organ able to regenerate after severe traumatic injuries. However, regeneration is governed by the interplay between systems located in the site of injury. The immune system initiates the inflammatory response in the early phase of healing. Therefore, the global role of T-cells and B-cells in the bone regeneration and the resulting bone quality is the focus of this study. A standard unilateral closed fracture was created in the femora to study the overlapping phases of bone healing. Besides wild type (WT) a model of recombination activating gene 1 knockout (RAG1-/-) mice that lacking mature T and B-cells were investigated. In addition, at D7 the individual role of T-cells and B-cells were investigated through the (TCRβδ) and JHT-/- knockouts respectively. Radiological, biomechanical, histological and imaging were utilized along with differential expression analysis. RAG1-/- mice showed higher biomechanical stiffness in intact bone when compared to the WT mice. Higher mineralization at early stage was seen in the RAG1-/- and bone devoid of T-cells (TCRβδ-/-) including. However, healing in bone devoid of B-cells (JHT-/-) was not apparently deviant of that of WT. Interestingly, second harmonic photon microscopy revealed an disorganized collagen fibers in the RAG1-/- contemporary with the expression analysis showing dysregulation in the expression of ColI subunits. Gene network analysis reflected the expected down regulation of T cell related genes in the RAG1-/- but not the B-cell related genes. This can hint to backup mechanism compensating the lack of mature B-cells. Furthermore, differentially expressed genes in RAG1-/- mice showed an impact on angiogenesis, cytokines & growth factors and bone remodeling, and BMP signaling array throughout the healing process. This asserts the focus on the adaptive immune system in two directions: 1) suggested role of T-cells in governing bone quality. 2) indicated importance of B-cells for bone regeneration through backup mechanisms.

Project description:Osteoporotic fractures are a growing issue due to the increasing incidence of osteoporosis worldwide. High reoperation rates in osteoporotic fractures call for investigation into new methods in improving fixation of osteoporotic bones. In the present study, the strength of a recently developed bone bioadhesive, OsStictm, was evaluated in vivo using a novel bone core assay in a murine animal model at 0, 3, 7, 14, 28, and 42 days. Histology and micro-CT were obtained at all time points, and the mean peak pull-out force was assessed on days 0-28. The adhesive provided immediate fixation to the bone core. The mean peak bone core pull-out force gradually decreased from 6.09 N (σ 1.77 N) at day 0 to a minimum of 3.09 N (σ 1.08 N) at day 7, recovering to 6.37 N (σ 4.18 N) by day 28. The corresponding fibrin (Tisseel) control mean peak bone core pull-out characteristic was 0.27 N (σ 0.27 N) at day 0, with an abrupt increase from 0.37 N (σ 0.28) at day 3, 6.39 N (σ 5.09 N) at day 7, and continuing to increase to 11.34 N (σ 6.5 N) by day 28. The bone cores failed either through core pull-out or by the cancellous part of the core fracturing. Overall, the adhesive does not interrupt healing with pathological changes or rapid resorption. Initially, the adhesive bonded the bone core to the femur, and over time, the adhesive was replaced by a vascularised bone of equivalent quality and quantity to the original bone. At the 42 day time point, 70% of the adhesive in the cancellous compartment and 50% in the cortical compartment had been replaced. The adhesive outwith the bone shell was metabolized by cells that are only removing the material excess with no ectopic bone formation. It is concluded that the adhesive is not a physical and biochemical barrier as the bone heals through the adhesive and is replaced by a normal bone tissue. This adhesive composition meets many of the clinical unmet needs expressed in the literature, and may, after further preclinical assessments, have potential in the repair of bone and osteochondral fragments.

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Dataset Information

Concise Review: Biomimetic Functionalization of Biomaterials to Stimulate the Endogenous Healing Process of Cartilage and Bone Tissue.

Publications

Concise Review: Biomimetic Functionalization of Biomaterials to Stimulate the Endogenous Healing Process of Cartilage and Bone Tissue.

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