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Clinical Applications of Cell-Scaffold Constructs for Bone Regeneration Therapy.

ABSTRACT: Bone tissue engineering (BTE) is a process of combining live osteoblast progenitors with a biocompatible scaffold to produce a biological substitute that can integrate into host bone tissue and recover its function. Mesenchymal stem cells (MSCs) are the most researched post-natal stem cells because they have self-renewal properties and a multi-differentiation capacity that can give rise to various cell lineages, including osteoblasts. BTE technology utilizes a combination of MSCs and biodegradable scaffold material, which provides a suitable environment for functional bone recovery and has been developed as a therapeutic approach to bone regeneration. Although prior clinical trials of BTE approaches have shown promising results, the regeneration of large bone defects is still an unmet medical need in patients that have suffered a significant loss of bone function. In this present review, we discuss the osteogenic potential of MSCs in bone tissue engineering and propose the use of immature osteoblasts, which can differentiate into osteoblasts upon transplantation, as an alternative cell source for regeneration in large bone defects.

SUBMITTER: Venkataiah VS

PROVIDER: S-EPMC8534498 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Clinical Applications of Cell-Scaffold Constructs for Bone Regeneration Therapy.

Venkataiah Venkata Suresh VS Yahata Yoshio Y Kitagawa Akira A Inagaki Masahiko M Kakiuchi Yusuke Y Nakano Masato M Suzuki Shigeto S Handa Keisuke K Saito Masahiro M

Cells 20211008 10

Bone tissue engineering (BTE) is a process of combining live osteoblast progenitors with a biocompatible scaffold to produce a biological substitute that can integrate into host bone tissue and recover its function. Mesenchymal stem cells (MSCs) are the most researched post-natal stem cells because they have self-renewal properties and a multi-differentiation capacity that can give rise to various cell lineages, including osteoblasts. BTE technology utilizes a combination of MSCs and biodegradab ...[more]

PMID: 34685667

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Project description:IntroductionBone defect repair remains a major challenge in modern medicine. Although bone marrow mesenchymal stem cells (BMSCs) possess multilineage differentiation potential, traditional BMSC constructs are often limited in clinical applications due to insufficient osteogenic differentiation efficiency and inadequate vascularization.MethodsThis study developed an innovative bone tissue engineering strategy by combining BMSCs with gelatin/polycaprolactone (GT/PCL) nanofiber membranes to form cell sheets, which were then modified with endothelial cells (ECs) on the surface. The sheets were subsequently rolled into three-dimensional scaffolds to systematically evaluate their osteogenic potential and underlying mechanisms.ResuiltsResults showed that electrospun GT/PCL nanofiber membranes exhibited uniform fiber structure (diameter 200-500 nm), successfully mimicking the microstructure of natural extracellular matrix. In vitro experiments demonstrated that after 14 days of culture, EC modification significantly enhanced the osteogenic differentiation of BMSCs compared to unmodified controls, with approximately 3-fold increase in ALP expression (p < 0.05) and 2.5-fold increase in angiogenic factor VEGF expression (p < 0.01). Subcutaneous implantation in nude mice revealed superior bone formation capability of EC-modified constructs at both 4 and 8 weeks: micro-CT analysis showed bone density reaching 350 mg/cm3, bone surface area approaching 400 mm2, and bone volume fraction of approximately 20%, significantly higher than control groups (p < 0.0001). Immunohistochemical evaluation further confirmed more mature trabecular bone structure and richer vascular networks in EC-modified groups.DiscussionMechanistic studies revealed that EC modification promoted bone regeneration through three key pathways: optimization of local vascular microenvironment for improved nutrient supply, activation of intercellular synergistic signaling pathways, and reconstruction of physiological bone tissue microenvironment. This study not only validates the application value of this composite strategy in bone tissue engineering but also provides important theoretical basis for developing novel bone regeneration solutions.

Project description:BackgroundAutologous grafting, despite some disadvantages, is still considered the gold standard for reconstruction of maxillofacial bone defects. The aim of this study was to evaluate bone regeneration using bone marrow-derived mesenchymal stromal cells (MSCs) in a clinical trial, a less invasive approach than autologous bone grafting. This comprehensive clinical trial included subjects with severe mandibular ridge resorption.MethodsThe study included 11 subjects aged 52-79 years with severe mandibular ridge resorption. Bone marrow cells were aspirated from the posterior iliac crest and plastic adherent cells were expanded in culture medium containing human platelet lysate. The MSCs and biphasic calcium phosphate granules as scaffolds were inserted subperiosteally onto the resorbed alveolar ridge. After 4-6 months of healing, new bone formation was assessed clinically and radiographically, as were safety and feasibility. Bone at the implant site was biopsied for micro-computed topography and histological analyses and dental implants were placed in the newly regenerated bone. Functional outcomes and patient satisfaction were assessed after 12 months.ResultsThe bone marrow cells, expanded in vitro and inserted into the defect together with biphasic calcium phosphate granules, induced significant new bone formation. The regenerated bone volume was adequate for dental implant installation. Healing was uneventful, without adverse events. The patients were satisfied with the esthetic and functional outcomes. No side effects were observed.ConclusionsThe results of this comprehensive clinical trial in human subjects confirm that MSCs can successfully induce significant formation of new bone, with no untoward sequelae. Hence, this novel augmentation procedure warrants further investigation and may form the basis of a valid treatment protocol, challenging the current gold standard.Trial registrationEudraCT, 2012-003139-50. Registered on 21 August 2013. ClinicalTrials.gov, NCT 02751125 . Registered on 26 April 2016.

Dataset Information

Clinical Applications of Cell-Scaffold Constructs for Bone Regeneration Therapy.

Publications

Clinical Applications of Cell-Scaffold Constructs for Bone Regeneration Therapy.

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