## 1 Introduction  
Musculoskeletal diseases including rheumatoid arthritis and osteoarthritis are a leading cause of functional decline and loss in quality of life [1]. Changes in lifestyles in the Western world population including increasing obesity and inactivity are putting populations at high risk of developing these conditions [2]. Specifically, osteoarthritis of the knee is projected to increase exponentially in the coming years; it is estimated that a tenth of the population aged over 50 years will be affected [3]. The direct cost of primary knee replacement is increasing, as well as the indirect costs, such as disability, rehabilitation and complications. The typical duration of the treatment gap (until surgical intervention is inevitable) in patients who undergo arthroplasty is 10 years [4]. However, using autologous blood derivatives can delay the need for total knee replacement surgery, and improve the quality of life by decelerating the progression of arthritis and ameliorating tissue repair in the tissues of the knee [5,6]. Human blood derivatives or blood products are fractions of human blood which have therapeutic uses, including red blood cell and thrombocyte concentrates, human serum albumin, coagulation factors, serum products, and immunoglobulin concentrates and other plasma products isolated both from whole blood or by apheresis. Plasma products are produced using anticoagulants, most commonly citrate or Ethylenediaminetetraacetic acid (EDTA). Serum products undergo the process of blood clotting, thus it contains activated platelets, while in plasma products, additional platelet activation may be needed, generally using thrombin. Blood derivatives are also widely used in laboratory experiments and cell therapies as medium supplementation as many cell cultures require a source of growth factors, hormones, vitamins, transport proteins and trace elements for their growth; this source is most commonly fetal bovine serum (FBS) [7]. However, the use of this non-human serum has some disadvantages in terms of clinical applicability, reproducibility and animal welfare concerns. There are many alternatives to FBS among human blood derivatives like human serum albumin (HSA) [8], serum [9], platelet-rich plasma [10], and serum from platelet-rich fibrin (SPRF) [11; 12; 13], which can evade the drawbacks of FBS and may have an even higher proliferative effect. Plasma products, especially platelet rich plasma (PRP), are in widespread use in tissue regenerative and reparative applications, such as in scar management [14], and orthopaedics, in musculoskeletal disorders like joint diseases or osteeonecrosis [15; 16]. The aim of using PRP in joint diseases is to relieve pain and improve the joint function. There are several methods to isolate PRP [17], but the high platelet concentration is common, and thus it is often used by physicians for treating knee and hip osteoarthritis with altering results [6], as the activated platelets release a combination of growth factors and cytokines [18], which induce various responses in the tissues of the joint. Platelet rich fibrin (PRF) membrane is a serum product which is used most commonly in hard and soft tissue engineering [19; 20; 21], such as wound healing [22], and dentistry, in oral, maxillofacial [23; 24] and in periodontal plastic surgeries [20; 25; 26]. PRF is a biodegradable scaffold with noted cell adhesive and proliferative effects promoting revascularization [27; 28]. Another advantage of PRF and its derivatives is that they do not require anticoagulants and bovine thrombin during their isolation. The serum derived from PRF (called SPRF: serum from platelet-rich fibrin, or PRF exudate) is another option for soft and hard tissue regeneration [29], as it was found to have an outstanding cell proliferative effect on human mesenchymal stem cells [30], osteoblasts, chondrocytes and adipocytes [5; 11; 12; 13]. It can be used in bone grafting [31] and implant surface functionalization [32], in dental applications [33], or treating osteoarthritis [5].