Regenerative Medicine

Prof. Dr. Stefano Zanasi is a pioneer in biological resurfacing with scaffolds perfused with combined stem cells of Knee and ankle.

Biological Knee and Ankle Resurfacing in severe Osteoarthritis

Dr. Stefano Zanasi first began performing hip, knee and ankle resurfacing procedures in 1994 using first ACT, then he used processed Bone Marrow to perfuse different scaffolds. After some years he investigated new source by Adipose derived stem cells and finally set combined MSCs (BMSCs plus ADSCs and PRP) resurfacing for scaffolds or allograft perfusion through bioengineering advanced technique . Typization of the stem cells by flowcitometry allows to give patients a certificate of the outcome and reproducibility of the procedure. The rationale behind the procedure was that it would be a total-conserving alternative to UNI or TKA for patients with higher activity demands i.e. young patients with severe uni- or bicompartmental osteoarthritis who are otherwise in good health. This would buy time until they reached an age at which they would be more suitable for a TKR or ankle replacement.

1. Biological resurfacing in severe knee and ankle or as alternative to traditional implant arthroplasty

An innovative personal clinical experience has provided evidence that widest areas of cartilage reconstruction in severe defects due to osteoarthritis of the inferior limb, Kellgren stage I to III, in particular knee and ankle, can be successfully restored through the combinatorial transplant of human bone marrow derived stem cells and adipose tissue derived stem cells: both are embedded within nanofabricated scaffolds with tailored oriented architecture and fiber diameter (Chondrotissue by ­Biotissue, Freiburg,D http.// This scaffold is a 100% syntetic and resorbable membrane that is cut in an appropriate size following the area of the lesion and loaded by a perfusion device with a different share of bone marrow concentrate and adipose stromal tissue Regenerative Fraction source. The loaded scaffold/s is/are placed in situ and sealed with fibrin glue and stay sutures or resorbable T pins to resurface a single/multiple wide loss/es of cartilage tissue. In severe osteoarthritis where the surface is completely bald and there are no health cartilage shoulders, the reconstruction is made by a personal indentation technique in which patches are stabilized at each corner by resorbable micro anchors after encasement of the last. The mean size of the lesions in our cases serie is 9.5cm2 (range 4.5–34 cm2).Patients are then directed to a specific rehabilitation program.

On these bases, the combinatorial use of autologous non-expanded tissue products made of whole bone marrow and human WAT derivatives, such as the adipose stromal tissue Regenerative Fraction source product (My STEM), can be considered as an autologous/homologous strategy for improving the natural capacity for self-healing in damaged osteo-articular tissues. These results suggest that MSCs resurfacing procedure even in severe unicompartmental OA demonstrates as an effective treatment for a biological coating that provides at least at medium-term data, remission of pain and swelling, with good functional recovery and an overlapping outcome vs ACT procedure with the advantage of a single operative step, and consequent and important cost reductions.

2. Biological reconstruction in osteonecrosis and postraumatic bone nonunion

The treatment of bony defects and bone healing disorders represents one of the biggest challenges in orthopedics and trauma surgery. In order to gain sufficient bone material, previously established operative procedures involved the transplantation of autogenous or allogenic bone, the additional use of bone substitution materials. In contrast to the osteoconductive bone substitution materials (allogenic bone, different synthetic/natural biomaterials), recombinant growth factors from the group of bone morphogenic proteins (BMPs) induce the formation of new bone .Their possible mechanism of action is via local activation of mesenchymal precursor cells. The physiological bone repair process is impaired in delayed or nonunion (NU) fractures and aseptic bone necrosis (ON) . Although the physiopathological factors are different, inboth diseases, bone lesions are not repaired in the right time nor in the right manner. SEVERAL METHODS COULD BE USED TO INCREASE MSCs POPULATION AND ITS OSTEOGENIC DIFFERENTIATION IN THE PATHOLOGICAL AREA: (i)a local injection of concentrated bone marrow aspirates, (ii) a preliminary culture of the bone marrow aspirate, (iii) a preliminary culture of the bone marrow aspirate to produce an expansion and an osteogenic differentiation of the MSCs, (iv) a genetic modification of the injected MSCs to increase the secretion of growth factors like BMP and VEGF. MSC differentiation in the specific track may be achieved as a result of environment, mechanical stimulation, and GF present in the platelet gel, able to stimulate cells toward osteogenesis and chondrogenesis. The potential of a multipotent cell may be considered not only an intrinsic capability of the cell alone but also the interaction between a cell with its physiologic niche that provides a signaling network (ie, the extracellular matrix, adhesion molecules, growth factors, cytokines, and chemokines secreted by the resident cells) Autologous bone marrow contains not only stem cells and precursor cells as a source of regeneration tissue, but also accessory cells that support angiogenesis and vasculogenesis by producing several growth factors. This suggests no cell selection and expansion in the laboratory may be required (as with ACT), and consequently the transplant can be performed in one operative procedure


London Stem Cell Clinic / Resume