Periodic Reporting for period 1 - ART-BONE (Manufacturing of Artificial Bone for Repair and Regeneration of Large Osseous Defects)
Reporting period: 2018-09-03 to 2020-09-02
Bone repair and regeneration with postoperative restoration of original structure and functions is a significant clinical goal in traumatology, orthopaedics and oral and maxillofacial surgery. Bone's self-healing capacity can be compromised in the context of large, critical-size osseous defects and non-union fractures caused by trauma, infection, osteoradionecrosis, ablative oncologic surgery, congenital abnormality, or metabolic bone diseases. These defects and fractures often result in long-term aesthetic deformities and/or functional damages which deeply affect patients’ emotional and physical well-being. To treat these defects and promote bone regeneration, there exists an urgent and ever-increasing demand for ‘off-the-shelf’ and cost-effective biomaterial-based therapies to substitute the ever-increasing number of costly and painful autologous bone grafting procedures. Bone grafting is a surgical intervention to reconstruct a damaged or diseased bone with a new bone from the patient′s own body (autografts) or a deceased donor (allografts), a skeletal material of animal origin (xenografts), or a man-made, synthetic substitute (alloplasts, commonly named biomaterials). These biomaterials have evolved through four different generations as follows: bioinert, dense ceramics, metals, alloys, stainless steels and ultra-high-molecular-weight polymers (1st generation); bioactive, dense or porous ceramics, bioglass and cements, or bioresorbable polymers (2nd generation); bioactive and bioresorbable, porous hybrid materials (3rd generation); biomimetic materials so far limited to a handful of second- and third-generation biomaterials functionalized with soluble, secreted signalling polypeptides (or, growth factors) whose role is to trigger new bone formation (4th generation).
The goal of the ART-BONE project was to develop and evaluate a new class of fourth generation biomaterials for bone repair. To reach this goal, the fellow achieved three different objectives: the fellow designed (objective 1), characterized (objective 2) and evaluated (objective 3) bone-mimetic biomaterials in the form of inorganic-organic composite materials. The fellow has also compared these bone-mimetic biomaterials with traditional biomaterials for bone repair and regeneration.
As a conclusion, this action provides a new mechanistic understanding of the physicochemical processes underlying osteogenesis. Further, this action has had a major impact in the researcher’s career since it allowed him to secure a permanent academic position within less than a year after the end of the action.
The goal of the ART-BONE project was to develop and evaluate a new class of fourth generation biomaterials for bone repair. To reach this goal, the fellow achieved three different objectives: the fellow designed (objective 1), characterized (objective 2) and evaluated (objective 3) bone-mimetic biomaterials in the form of inorganic-organic composite materials. The fellow has also compared these bone-mimetic biomaterials with traditional biomaterials for bone repair and regeneration.
As a conclusion, this action provides a new mechanistic understanding of the physicochemical processes underlying osteogenesis. Further, this action has had a major impact in the researcher’s career since it allowed him to secure a permanent academic position within less than a year after the end of the action.
Objective 1. Highly mineralized (i.e. 50% wt.) inorganic-organic composite materials were prepared using bone-like calcium phosphate particles developed by the fellow.
Objective 2. The bone-mimetic composite materials prepared in objective 1 were characterized using a set of physical characterization techniques, including solid-state Nuclear Magnetic Resonance (NMR) spectroscopy and scanning helium ion microscopy (SHIM).
Objective 3. The bone repair ability of the bone-mimetic composite materials fabricated in objective 1 and characterized in objective 2 were evaluated and compared to that of composite materials made of commercially available hydroxyapatites in preclinical studies. To this end, a classical bioengineering approach was applied: human bone marrow mesenchymal stem cells (hMSCs) were cultured on the composite materials over a period up to 21 days. Cells’ proliferation and viability were examined using DNA quantification. Cells’ osteogenic differentiation was assessed in terms of alkaline phosphatase (ALP) activity, collagen production and calcium phosphate deposition, but also in terms of osteogenic genes expression levels.
The work of the fellow through the ART-BONE project has been translated into five peer-reviewed scientific publications to date, with two more publications which are currently under preparation. The fellow has also presented the outcomes of the project in one national conference and in one international conference.
Objective 2. The bone-mimetic composite materials prepared in objective 1 were characterized using a set of physical characterization techniques, including solid-state Nuclear Magnetic Resonance (NMR) spectroscopy and scanning helium ion microscopy (SHIM).
Objective 3. The bone repair ability of the bone-mimetic composite materials fabricated in objective 1 and characterized in objective 2 were evaluated and compared to that of composite materials made of commercially available hydroxyapatites in preclinical studies. To this end, a classical bioengineering approach was applied: human bone marrow mesenchymal stem cells (hMSCs) were cultured on the composite materials over a period up to 21 days. Cells’ proliferation and viability were examined using DNA quantification. Cells’ osteogenic differentiation was assessed in terms of alkaline phosphatase (ALP) activity, collagen production and calcium phosphate deposition, but also in terms of osteogenic genes expression levels.
The work of the fellow through the ART-BONE project has been translated into five peer-reviewed scientific publications to date, with two more publications which are currently under preparation. The fellow has also presented the outcomes of the project in one national conference and in one international conference.
The project’s outcomes show that the composite materials made of bone-mimetic hydroxyapatite particles have the potential to outperform those made of poorly biomimetic hydroxyapatite. These bone-mimetic materials are particularly timely to supply the urgent and ever-increasing demand for ‘off-the-shelf’ and cost-effective biomaterial-based therapies for bone repair and regeneration, and the ART-BONE project provides design principles to elaborate such biomaterial-based therapies.