Collagen, a key factor for clinical success

Tecnoss® exclusive manufacturing process is able to neutralize the antigenic components present in heterologous bone (achievement of biocompatibility) and to preserve the collagen matrix inside the granules of biomaterial.
Moreover, the molecular structure of natural hydroxyapatite is not significantly altered thanks to the limited maximum process temperature1.
These characteristics of Tecnoss® products allow a consistent bone neo-formation and a close contact between mature neo-formed bone and biomaterial granules.
Collagen has a key role in bone regeneration process in that: a) it acts as a valid substrate for platelet activation and aggregation b) it serves to attract and differentiate the mesenchymal stem cells present in the bone marrow2 c) it increases the proliferation rate of the osteoblasts up to 2/3 times3 d) it stimulates the activation of the platelets, osteoblasts and osteoclasts in the tissue healing process
The presence of collagen inside each granule makes Tecnoss® Bone Matrix hydrophilic and facilitates further mixing with collagen gel (Tecnoss® Gel 0). This technology has permitted the development of two new versatile and innovative products: Tecnoss® mp3 and Tecnoss® Putty. Their consistency allows an ideal filling of bone defects and spinal cages and guarantees simple handling and fast application.
Guided Bone Regeneration (GBR) is necessary to treat bone deficits due to lesions or bacterial infections.
The bone defect recovery occurs through the general mechanisms of tissue healing, that is, by complex dynamic mechanisms directed towards the repair of tissue function and anatomic integrity.
The discovery of the events pathway leading to tissue healing has helped to clearly identify the main actors in bone healing process; the concomitant presence of the following three components is necessary for the formation of “de novo” bone tissue:
>> the platelets represent the principal actors during the first phase of the healing process, when, subsequent to a lesion, an initial deposition of fibrin and the formation of blood clot take place. This phase is characterized by significant activation of the chemical signals mediated by cytokines and growth factors.
In fact, the primary post-haemorrhagic clot formation process through platelet aggregation and lysis causes the release of both the coagulation cascade factors and growth factors, such as PDGF, IGF 1, IGF 2 and VEGF which are known for their activating effect on osteoblasts and osteoclasts, and TGF-β (Bone Morphogenetic Proteins belong to this superfamily) which starts bony callus formation.
>> the osteoblastic precursors deriving from bone marrow mesenchymal stem cells are responsible, after cell differentiation in osteoblasts, for the second phase of the healing process (enchondral and/or intermembrous ossification) thanks to the synthesis of collagen and other components of the extracellular matrix.
>> an insoluble substrate, suitable carrier for osteoinductive signal and able to support and guide new bone tissue formation.
Sampath and Reddi (1980) demonstrated crosslinked type I collagen to be the most appropriate carrier for promoting osteoinductive signal activity.
The continuous progresses in comprehension of biological mechanisms regulating bone tissue morphogenesis can be exploited also for elaboration of natural or artificial products able to restore or maintain the function of damaged tissues and organs (tissue engineering)4,5,6.
In vitro studies demonstrated that heterologous collagen is able to induce differentiation of mesenchymal osteoprogenitor stem cells into osteoblasts2, and that association of collagen type I with a scaffold of hydroxyapatite significantly enhances osteoblasts proliferation rate3.
This important scientific evidence provides the rationale behind Tecnoss® product line: a complete series of biomaterials with collagen base.
Collagen, in addition to its well-known structural action carried on connective tissues, is endowed with the following important properties, useful in tissue reparation processes:
1. Haemostasis: collagen is able to activate the receptors present on cellular membranes of platelets, responsible for their aggregation and lysis process; moreover, during the first week, it reinforces the action of fibrin in the formation of the primary clot, and then, in the second week, it replaces the function of fibrin.
2. Debridement: collagen has a chemotactic action on monocyte/macrophage cell lines, from which osteoclasts derive; these cells, through their action on mineral component resorption of both bone tissue and Tecnoss® biomaterials, can draw, activate and collaborate with osteoblasts in bone rearranging and remodeling.
3. Angiogenesis: the drawn monocytes/ macrophages, in their turn, stimulate both osteoblastic activity and angiogenesis process in grafting site.
4. Osteoblastic activity: collagen, binding to fibronectin, promotes the anchorage of mesenchymal stem progenitors, on which it exerts its chemotactic action, and induces differentiation into osteoblasts2.
5. Receiving site remodeling: exogenous collagen grafting can contribute in decreasing remodeling times of immature bone tissue.
6. Osteoconduction and guided regeneration: naturally integrated with mineral component, collagen is able to increase osteoblasts proliferation rate3, while as a resorbable membrane it is able to guide connective tissue regeneration.

Therefore all collagenated biomaterials of Tecnoss® product line provide 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.
BIBLIOGRAPHY
1 | FIGUEIREDO M ET AL |  JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B: APPLIED BIOMATERIALS (2009)
2 | SALASZNYK RM ET AL | JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY (2004)
3 | HSU FY ET AL | BIOMATERIALS (1999)
4 | GRIFFITH LG ET AL | SCIENCE (2002)
5 | REDDI AH | TISSUE ENGINEERING (2000)
6 | NAKASHIMA N ET AL | NATURE BIOTECHNOLOGY (2003)

SEM image of a Tecnoss® Evolution collagenic matrix Nobil Bio Ricerche, Villafranca d’Asti, Italy