The skeletal bone of a living human is constantly being remodeled. Osteoblasts and osteoclasts are the cells responsible for the formation and reabsorption of bone. Together they maintain a dynamic equilibrium in the healthy skeleton of adults. Collagen has a vital role in these processes as well, since it forms the structural protein framework of bone, and it takes part in the interaction between osteoblasts and osteoclasts. Despite the tissues great ability to self-repair, the bone does not always respond appropriately when affected by extensive trauma or osteolysis. These situations triggered the search for high quality bone grafts that can fi ll these gaps and restore availability. Hypro-Oss, the innovative natural bovine bone graft incorporated with biocompatible Atelocollagen Type I, was especially processed to provide millions of patients around the world with an appropriate solution.
Skeletal bone tissue basically consists of Collagen Type I organic matrix, which contains low molecular weight proteoglycans and non-collagen proteins, a mineral part (mainly hydroxyapatite, HA) and water, respectively corresponding to 10%, 25% and 65% and of the bone weight. The protein components of animal tissues are the determinants of individual uniqueness. They also serve as an antigen, being the bone graft component, thus responsible for activating the immune system’s cells of the receiving organism by interacting with receptors of the major histocompatibility complex (MHC), so that the protein is responsible for the unwanted immune reaction. The suppression of the antigenic properties of the immunogenic protein component of collagen molecules in bone graft material enables the implantation of mineral bone and collagen matrix in patients without any risk of adverse reactions.
Both BIOIMPLON GMBH and HYPRO OTROKOVICE S.R.O. have extensive experience in developing and processing unique biocompatible biomaterial products, and especially in modifying immunogenic collagen products into non-immunogenic atelocollagen. Thanks to the atelopeptidation patent by HYPRO OTROKOVICE we were able to devise our unique proprietary technology for sophisticated manufacturing processes of soft and hard tissue biomaterials. Twenty years experience with these safe, biocompatible Hypro-Sorb collagen products, encouraged us to devise Hypro-Oss, using the same atelopeptidation patented technology, thus allowing it to obtain the highest levels of collagen biocompatibility, while preserving the natural crystalline, triple helical collagen matrix structure and expanding the macro/micro-porosity surface of the bone granules by means of nonheating of the biomaterial, but by implementing the lyophilization technology for processing the material.
Our concept for the development of the Hypro-Oss product line was conceived with the idea of an ideal biomaterial in mind, a material with the highest biocompatibility and affinity to the new endogenous bone. In order to accomplish this purpose, we implemented our proprietary atelopeptidation and lyophilization technologies that preserve natural collagen components of bone material within bone structure after modifying the collagen to a non-immunogenic atelocollagen. This preserves the natural crystalline structure of the hydroxyapatite as well as the collagen components by completely avoiding the heating (thermo) processing method that other manufacturers still use.
Thanks to our innovative proprietary processing technology, Hypro-Oss has the following important characteristics:
• Native bovine graft composite for enhanced new bone formation
• Telopeptide free collagen components; non-immunogenic peptide
• Acceleration of physiological tissue healing process
• Protects grafting site from infection (bacteriostatic effect of atelocollagen)
• Capability to carry medication to the surgical site
• Highest biocompatibility; absence of a foreign body response
• Preserves the natural structures of atelocollagen and hydroxyapatite due to lyophilization processing
• Powerfull haemostatic effect of the atelocollagen that averts haematoma formation after surgical procedures
These characteristics allow enhanced and consistent new bone formation, and persistent integration between mature new formed bone and existing bone materials.
Atelopeptidation is a term that describes the physicochemical deletion of the immunogenic/antigenic terminal peptide sequence (telopeptide) in a collagen molecule. The resulting modified collagen is called an atelocollagen, a safe non-immunogenic collagen that can be implanted in patients without any adverse reactions. Our patented biological atelopeptidation technology allows us to physicochemically delete the antigenic peptide segment, located at the terminal peptide of collagen molecules within the bone compound, and therefore preserve the native collagen matrix structure inside the granules, making it biocompatible. Moreover, thanks to the unique lyophilization processing technology thus implemented, the crystalline molecular structures of the natural hydroxyapatite and collagen are preserved without any alteration. Heat (Thermal processing) was not used in processing our biomaterial products, as other manufacturers do. It is well known that heating bone materials negatively affects the natural crystalline micro-structure of hydroxyapatite, causing bone ceramization, in addition to destroying collagen components. Our atelopeptidation patent enables us to turn immunogenic collagen into a safe collagen, telopeptide free collagen (atelocollagen), and an absolutely biocompatible collagen without any risk of adverse reactions.
Many methods have been proposed and used around the world for processing and storing bone tissue for clinical application. Lyophilization is the optimal choice. It is a technique that evaporates water contained in a product by sublimation, i.e. a previously frozen material is placed in a vacuum, which turns the ice to vapor. Moreover, lyophilization provides mainly bovine material with biocompatibility, andit also enables storage at room temperature. The presence of lyophilized collagen with lower humidity inside each granule makes Hypro-Oss bone matrix hydrophilic and facilitates further activation of platelets. Its consistency allows an ideal filling of bone defects and guarantees simple handling and fast application.
Hypro-Oss is non-immunigenic, sterile and does not support the growth of infectious microorganisms due to the crystalline tripple helix structure of the Atelo-collagen components, on the contrary, Hypro-Oss exhibits a mild antimicrobial effect as it binds to and inactivates the enzymes necessary for the metabolism of the microorganisms. This property conferes Hypro-Oss its bacteriostatic effect and so contributes to an uninterrupted wound healing and accelerated bone formation as well.
Atelocollagen’s Vital Role in Bone Regeneration Process
Atelocollagen Type I is the most appropriate carrier for promoting osteoinductive signal activity. In vitro studies show that collagen is capable of inducing differentiation of mesenchymal osteoprogenitor stem cells into osteoblasts, and that the association of Atelocollagen Type I with a scaffold of natural hydroxyapatite signifi cantly enhances the proliferation rate of osteoblasts. This important scientific evidence provides the rationale behind the development of Hypro-Oss products’ line. Hypro-Oss atelocollagenated bone graft provides the natural substrate for correct bone tissue regeneration and repair, facilitating and accelerating the physiological regeneration process, and allowing optimal results within a reasonable period of time. The Hypro-Oss atelopeptidation manufacturing process eliminates antigenic components that are present in bone collagen (thanks to the patent of HYPRO OTROKOVICE in 1992) and preserves the collagen matrix inside the biomaterial’s granules. Moreover, thanks to the unique lyophilization processing technology utilized for Hypro-Oss processing, the molecular structure of natural hydroxyapatite is not altered at all. These characteristics of Hypro-Oss enable consistent bone neoformation and close contact between mature new-formed bone and biomaterial granules.
Atelocollagen acts as valid substrate for platelet activation and aggregation. Degradation of platelets provide vital growth peptides, such as PDGF, IGF 1, IGF 2 and VEGF, which are known for their activating effect on osteoblasts and osteoclasts, and TGF beta, which starts bony callus formation. It also serves to attract and differentiate mesenchymal stem cells that are present in the bone marrow, and to increase the proliferation rate of osteoblasts.
In addition to its well-known structural effect on connective tissues, collagen is endowed with the following important properties, which are helpful in tissue reparation processes:
a- Hemostasis: Collagen can activate the receptors on cellular membranes of platelets, which are responsible for their aggregation and degradation processes.
b- Debridement: Collagen acts chemo-tactically on monocyte/macrophage cell lines from which osteoclasts derive. These cells, through their activity on mineral component reabsorption of both bone tissue and Hypro-Oss biomaterials, activate and collaborate with osteoblasts in bone rearranging and remodeling.
c- Neovascularization: In their turn, the monocytes/macrophages stimulate both osteoblastic activity and an angiogenesis process in grafting site.
d- Osteoblastic activity: Collagen, binding to fibronectin, promotes the anchor of mesenchymal stem progenitors, on which it exerts its chemotactic effect, and induces differentiation into osteoblasts.
Clinical routine shows that stability plays an important role during the early stages of implantology treatment. The quicker and more intensive the osseointegration process, the higher the stability of the implant. Hypro-Oss is an incomparably stable, highly purified, and well established HA/collagen bone graft material of bovine origin. It goes further towards satisfying the requirements for increased safety, enhanced new bone formation and integration and better predictability. The material is used for Oral Guided Bone Regeneration (GBR) in the management of simple and complicated defects to build up the bone bed. The mineral composition, the crystalline structure, and the integrated biocompatible collagen structure of Hypro-Oss are very similar to those of the human body. Therefore, after the integration of Hypro-Oss, the same elasticity, strength and stability as of the patient’s own bone are achieved. Hypro-Oss is eminently suitable for all augmentation techniques, for building up a strong implant bed and for treating periodontal defects. Hypro-Oss is the material of choice for functional and aesthetic reconstructions, for natural, reliable, simple and economic bone regeneration. Thanks to the atelopeptidation and the lyophilization processes, Hypro-Oss is confirmed to have a particularly high degree of pure biocompatible collagen, hydroxyapatite components of bovine origin and physiological pH. Hypro-Oss is superior to hydroxyapatite ceramics thanks to the outstanding homogeneity of the hydroxyapatite, collagen structures and the interconnecting macropores of the natural bone.
The innovative development of a two-phase hydroxyapatite with incorporated collagen such as Hypro-Oss was prompted by the trend towards accelerated new bone formation, increased safety and better predictability. The focus on the body’s biological healing processes demanded a material that does not contaminate the healing process in the body with phase impurities. The HA-phase content of Hypro-Oss, as measured by X-ray diffractograms, shows phase pure hydroxyapatite. The Energy Dispersive Spectroscopy (EDS) analysis confirms homogeneity of the two-phase hydroxyapatite + collagen composition. Hypro-Oss is pure, sterile and 100% BSE safe. Thus Hypro-Oss does not contain any phase constituents that impair the healing process .This implies better clinical safety for therapist and patient alike. In this way Hypro-Oss exploits the human body’s natural and perfect healing potential, right from the start.
The excellent acceptance and biocompatibility of natural bovine bone graft of Hypro-Oss derive from its material processing properties. Hypro-Oss’s other properties are based on the open interconnecting pore structure, which is identical to the biological characteristics of the bovine starting material and arise from the physiological structure of the human body. Hypro-Oss’s macroporous structure is ideal in its osteoconductive function and promotes the ingrowth of blood vessels. Native bone collagen stimulates and accelerates new bone formation by triggering the thrombocytes aggregation, the degradation and the release of growth peptides such as Beta TGF and BMP, which are responsible for enhanced bone formation. The adhesion and spread of osteoblasts over the Hypro-Oss surface creates an open, interconnecting pore structure, thus prompting a bioactive reaction with bone tissue formation, bone tissue strengthening and bone tissue interlinking, thus leading to the restoration of the bone and its function. The osteoconductive properties of hydroxyapatite and the osteoinductive properties of the collagen act together in harmony for enhanced, high quality bone formation for the patients’ benefit.
The very good reception of Hypro-Oss is evident in its efficacy. Hydroxyapatite of bovine origin has been successfully used in clinical medicine since 1958. Radiological follow-ups showed consolidation of the defects consistent with the healing phase. Biopsies retrieved from clinical grafts showed that the hydroxyapatite had almost completely been surrounded by bone and that newly formed bone had also been deposited inside the granule pores. The long-term results were also confirmed by clinical applications. Hypro-Oss implantation tests and the results of histological studies confirm enhanced new bone formation effect of the collagen component within the bovine bone graft in Hypro-Oss.
Hypro-Oss’s bone graft material is extremely well tolerated. Its pH matches the physiological levels, which is particularly important during the early stages of implantation. Hypro-Oss does not contain any pharmacologically active constituents that could cause any risk to patients. A great number of patients have confirmed the biocompatibility of Hypro-Sorb products that consist of the same atelocollagen as Hypro-Oss. Not one single adverse reaction has been reported for many years.
Hypro-Oss’s material is hydrophilic and it can be easily mixed with the patient’s blood before insertion. This Hypro-Oss blood mixture has excellent coagulation properties thus expediting extremely accurate placement. Bone regeneration can be promoted in combination with blood or sterile saline.
The raw material comes from EU animal farms, selected and certified under the strict control of the Czech National Veterinary Health Service. All manufacturing processes are executed in conformity with the Quality Management Systems under the control of the Higher Health Institute, which verifies compliance with current CE regulations and approves and authorizes the products’ marketing. Hypro-Oss is a natural hydroxyapatite / collagen composite that consists entirely of homogenic material that is available as granules of various sizes or pre-formed shapes. Due to its non-altered hydroxyapatite/collagen composition and particularly high degree of purity, its physiological pH, its homogeneity of hydroxyapatite and collagen structures and its interconnecting macropores, Hypro-Oss is superior to any other hydroxyapatite ceramic. Hypro-Oss’s chemical composition, porosity, size, shape and biological behavior are similar to its human counterparts. In addition to these features, Hypro-Oss provides structural support, osteoconduction and osteoinduction properties and a high content of calcium and phosphorus, all of which are essential factors for the newly formed bone tissue.
• Natural bovine bone grafting material with incorporated biocompatible collagen
• Atelo-collagenated and lyophilized grafting material
• Pure bone mineral and pure Collagen Type I composition
• Directed integration and enhanced new bone formation
• Osteoinductive atelocollagen components
• Osteoconductive hydroxyapatite components
• No foreign body or infl ammatory reaction
• Hydrophilic, optimal cell adhesion and blood absorption
• Native crystalline structure interconnective porosity
• Long-term dimensional stability
• Safe and sterile
• Easy handling
• Implantology, Periodontology and Oral Surgery
• Sinus lift
• Horizontal augmentation
• Intraosseous defects
• Peri-implant defects
• Extraction sockets
• Vertical augmentation
• Furcation defects
• Filling of cyst
• Periodontal defects
Indications in orthopedic surgery and traumatology as:
- Filling od bone defects in juxta-articular fractures
- Filling of defects of the acetabulum on change of prosthesis
- Filling of bone defects after excision of bening tumors
- Filling of bone cysts
- Filling of tissue defects in cartilage and bone transplants
- Filling of bone defects at donor sites after harvest of autogenous bone