Bioactive Coatings Loaded with Osteogenic Protein for Metallic Implants

Osteoconductive and osteoinductive coatings represent attractive and tunable strategies towards the enhanced biomechanics and osseointegration of metallic implants, providing accurate local modulation of bone-to-implant interface. Composite materials based on polylactide (PLA) and hydroxyapatite (HAp) are proved beneficial substrates for the modulation of bone cells’ development, being suitable mechanical supports for the repair and regeneration of bone tissue. Moreover, the addition of osteogenic proteins represents the next step towards the fabrication of advanced biomaterials for hard tissue engineering applications, as their regulatory mechanisms beneficially contribute to the new bone formation. In this respect, laser-processed composites, based on PLA, Hap, and bone morphogenetic protein 4(BMP4), are herein proposed as bioactive coatings for metallic implants. The nanostructured coatings proved superior ability to promote the adhesion, viability, and proliferation of osteoprogenitor cells, without affecting their normal development and further sustaining the osteogenic differentiation of the cells. Our results are complementary to previous studies regarding the successful use of chemically BMP-modified biomaterials in orthopedic and orthodontic applications.

A Pilot Study of Seamless Regeneration of Bone and Cartilage in Knee Joint Regeneration Using Honeycomb TCP

The knee joint is a continuous structure of bone and cartilage tissue, making it difficult to regenerate using artificial biomaterials. In a previous study, we succeeded in developing honeycomb tricalcium phosphate (TCP), which has through-and-through holes and is able to provide the optimum microenvironment for hard tissue regeneration. We demonstrated that TCP with 300 μm pore diameters (300TCP) induced vigorous bone formation, and that TCP with 75 μm pore diameters (75TCP) induced cartilage formation. In the present study, we regenerated a knee joint defect using honeycomb TCP. 75TCP and 300TCP were loaded with transforming growth factor (TGF)-β alone or bone morphogenic protein (BMP)-2+TGF-β with or without Matrigel and transplanted into knee joint defect model rabbits. 75TCP showed no bone or cartilage tissue formation in any of the groups with TGF-β alone and BMP-2+TGF-β with/without Matrigel. However, for 300TCP and BMP-2+TGF-β with or without Matrigel, vigorous bone tissue formation was observed in the TCP holes, and cartilage tissue formation in the TCP surface layer was continuous with the existing cartilage. The cartilage area in the TCP surface was larger in the group without Matrigel (with BMP-2+TGF-β) than in the group with Matrigel (with BMP-2+TGF-β). Therefore, honeycomb TCP can induce the seamless regeneration of bone and cartilage in a knee joint.

Stability of Implants Supported By Three Types of Bone Grafting Materials in Dogs

Background: This study was conducted to assess the stability of implants placed in a simultaneous procedure with different grafting materials (autogenous, xenogenous, and synthetic) in experimentally induced bone defects in dogs.Methods: Thirteen dogs were included and divided into three groups according to the time of sacrificing. Oversized osteotomies were prepared in the sternum, and the implants were placed in bone defects. A total of 3 to 5 implants were placed per animal. Each group of animals contained 3 subgroups according to the grafting material utilized. In subgroup 1, autograft was applied, whereas in subgroups 2 and 3, bovine bone mineral (Cerabone) and a synthetic calcium phosphate substitute (Osteon II) were employed. At the end of the specified healing periods (2 months, 4 months, or 6 months), the animals were sacrificed and the implant stability was determined through measuring the resonance frequency.Results: Forty-five integrated implants were obtained from this study and nine were lost (failure rate 17%). The two-way analysis of variance revealed no significant difference in ISQ measurements either between the bone graft materials (autogenous, xenogenous, and synthetic; P=0.950) or between the healing intervals (2 months, 4 months, and 6 months; P=0.769)Conclusions: The stability of implants augmented with autogenous, xenogenous (Cerabone) or synthetic (Osteon II) graft materials was comparable at 2, 4 and 6 months after placement. This indicates that both Cerabone and Osteon II could be considered as suitable substitutes for regeneration of bone defects to overcome the limitations of autografts.

Pharmacological Approaches and Regeneration of Bone Defects with Dental Pulp Stem Cells

Bone defects in the craniomaxillofacial skeleton vary from small periodontal defects to extensive bone loss, which are difficult to restore and can lead to extensive damage of the surrounding structures, deformities, and limited functions. Plenty of surgical regenerative procedures have been developed to reconstruct or prevent alveolar defects, based on guided bone regeneration involving the use of autogenous bone grafts or bone substituents. However, these techniques have limitations in the restoration of morphological and functional reconstruction, thus stopping disease progression but not regenerating lost tissue. Most promising candidates for regenerative therapy of maxillofacial bone defects represent postnatal stem cells, because of their replication potential in the undifferentiated state and their ability to differentiate as well. There is an increased need for using various orofacial sources of stem cells with comparable properties to mesenchymal stem cells because they are more easily available with minimally invasive procedures. In addition to the source of MSCs, another aspect affects the regeneration outcomes. Thermal, mechanical, and chemical stimuli after surgical procedures have the ability to generate pain, usually managed with pharmacological agents, mostly nonsteroidal anti-inflammatory drugs (NSAIDs). Some studies revealed that NSAIDs have no significant cytotoxic effect on bone marrow stem cells from mice, while other studies showed regulation of osteogenic and chondrogenic marker genes in MSC cells by NSAIDs and paracetamol, but no effect was observed in connection with diclofenac use. Therefore, there is a need to focus on such pharmacotherapy, capable of affecting the characteristics and properties of implanted MSCs.

Toughening of Bioceramic Composites for Bone Regeneration

Bioceramics are widely considered as elective materials for the regeneration of bone tissue, due to their compositional mimicry with bone inorganic components. However, they are intrinsically brittle, which limits their capability to sustain multiple biomechanical loads, especially in the case of load-bearing bone districts. In the last decades, intense research has been dedicated to combining processes to enhance both the strength and toughness of bioceramics, leading to bioceramic composite scaffolds. This review summarizes the recent approaches to this purpose, particularly those addressed to limiting the propagation of cracks to prevent the sudden mechanical failure of bioceramic composites.

Regeneration of Bone Defects in a Rabbit Femoral Osteonecrosis Model Using 3D-Printed Poly (Epsilon-Caprolactone)/Nanoparticulate Willemite Composite Scaffolds

Steroid-associated osteonecrosis (SAON) is a chronic disease that leads to the destruction and collapse of bone near the joint that is subjected to weight bearing, ultimately resulting in a loss of hip and knee function. Zn2+ ions, as an essential trace element, have functional roles in improving the immunophysiological cellular environment, accelerating bone regeneration, and inhibiting biofilm formation. In this study, we reconstruct SAON lesions with a three-dimensional (3D)-a printed composite made of poly (epsilon-caprolactone) (PCL) and nanoparticulate Willemite (npW). Rabbit bone marrow stem cells were used to evaluate the cytocompatibility and osteogenic differentiation capability of the PCL/npW composite scaffolds. The 2-month bone regeneration was assessed by a Micro-computed tomography (micro-CT) scan and the expression of bone regeneration proteins by Western blot. Compared with the neat PCL group, PCL/npW scaffolds exhibited significantly increased cytocompatibility and osteogenic activity. This finding reveals a new concept for the design of a 3D-printed PCL/npW composite-based bone substitute for the early treatment of osteonecrosis defects.

Bioactive Calcium Phosphate-Based Composites for Bone Regeneration

Calcium phosphates (CaPs) are widely accepted biomaterials able to promote the regeneration of bone tissue. However, the regeneration of critical-sized bone defects has been considered challenging, and the development of bioceramics exhibiting enhanced bioactivity, bioresorbability and mechanical performance is highly demanded. In this respect, the tuning of their chemical composition, crystal size and morphology have been the matter of intense research in the last decades, including the preparation of composites. The development of effective bioceramic composite scaffolds relies on effective manufacturing techniques able to control the final multi-scale porosity of the devices, relevant to ensure osteointegration and bio-competent mechanical performance. In this context, the present work provides an overview about the reported strategies to develop and optimize bioceramics, while also highlighting future perspectives in the development of bioactive ceramic composites for bone tissue regeneration.

Main Approaches to the Use of Biomaterials in Oral and Maxillofacial Surgery: A Brief Systematic Review

Introduction: In recent years, procedures with the use of dental implants have increased worldwide, reaching approximately one million dental implants per year. In recent years, a platelet concentrate called FRP (fibrin-rich plasma) has been the subject of clinical studies. Associated with this, the biomaterial Bio-Oss® (Geistlich), as it is biodegradable, biocompatible, non-toxic, and has low immunogenicity, and bio stimulators can act in the regeneration of bone tissue, as it establishes with the cells the appropriate biological niche (favorable microenvironment) for bone growth. Objective: Therefore, the present study aimed to evaluate, through a brief systematic review, the results that involve bone formation for dental implantation, with the use of biomaterials such as fibrin-rich plasma and Bio-Oss®. Methods: The model used for the review was PRISMA. Was used databases such as Scopus, Scielo, Lilacs, Google Scholar, PubMed. Results: Fibrin-rich plasma (FRP) as an autologous biomaterial for use in oral and maxillofacial surgery presents most leukocytes, platelets, and growth factors, forming a fibrin matrix, with three-dimensional architecture. The Bio-Oss® biomaterial (Geistlich), as it is biodegradable, biocompatible, non-toxic, and has low immunogenicity and bio stimulators can act in the regeneration of bone tissue, since it establishes with the adenomatous mesenchymal stem cells the appropriate biological niche for bone growth and, thus, allowing the dental implant to be as effective as possible. Conclusion: The use of FRP associated with Bio-Oss® seems to illustrate high success rates with minimal costs, which may reduce the amount of bone graft needed to fill the sinus cavity, reducing the costs of the procedure.