Alberto Busilacchi

Chitosan, hyaluronan and chondroitin sulfate in tissue engineering for cartilage regeneration: A review

Injection of hyaluronan into osteoarthritic joints restores the viscoelasticity, augments the flow of joint fluid, normalizes endogenous hyaluronan synthesis, and improves joint function. Chitosan easily forms polyelectrolyte complexes with hyaluronan and chondroitin sulfate. Synergy of chitosan with hyaluronan develops enhanced performances in regenerating hyaline cartilage, typical results being structural integrity of the hyaline-like neocartilage, and reconstitution of the subchondral bone, with positive cartilage staining for collagen-II and GAG in the treated sites. Chitosan qualifies for the preparation of scaffolds intended for the regeneration of cartilage: it yields mesoporous cryogels; it provides a friendly environment for chondrocytes to propagate, produce typical ECM, and assume the convenient phenotype; it is a good carrier for growth factors; it inactivates metalloproteinases thus preventing collagen degradation; it is suitable for the induction of the chondrogenic differentiation of mesenchymal stem cells; it is a potent means for hemostasis and platelet delivery.

Chitosan stabilizes platelet growth factors and modulates stem cell differentiation toward tissue regeneration

The idea of using chitosan as a functional delivery aid to support simultaneously PRP, stem cells and growth factors (GF) is associated with the intention to use morphogenic biomaterials to modulate the natural healing sequence in bone and other tissues. For example, chitosan-chondroitin sulfate loaded with platelet lysate was included in a poly(D,L-lactate) foam that was then seeded with human adipose-derived stem cells and cultured in vitro under osteogenic stimulus: the platelet lysate provided to the bone tissue the most suitable assortment of GF which induces the osteogenic differentiation of the mesenchymal stem cells. PDGF, FGF, IGF and TGF-β were protagonists in the repair of callus fractures. The release of GF from the composites of chitosan-PRP and either nano-hydroxyapatite or tricalcium phosphate was highly beneficial for enhancing MSC proliferation and differentiation, thus qualifying chitosan as an excellent vehicle. A number of biochemical characteristics of chitosan exert synergism with stem cells in the regeneration of soft tissues.

Arthroscopic Knee Cartilage Repair With Covered Microfracture and Bone Marrow Concentrate

In recent years several single-stage cartilage repair approaches have been devised to treat focal cartilage lesions. These usually associate microfracture (MFX) and a coverage scaffold. We describe a novel arthroscopic technique that combines MFX, autologous bone marrow concentrate (BMC), and a protective scaffold. Bone marrow aspirate from the iliac crest is centrifuged to obtain BMC. The cartilage defect is debrided, MFX holes are created, and the final defect is measured by use of a bent K-wire. The scaffold is then shaped to match the defect, immersed in BMC, introduced into the joint with a grasper, and fixed in place with a mixture of fibrin glue and BMC. This technique aims to augment the original single-stage procedure with a number of mesenchymal stem cells and growth factors contained in the BMC, to increase the defect filling and the rate of hyaline-like cartilage regeneration. The procedure combining MFX, BMC, and a protective scaffold is inexpensive and reproducible and has already shown the ability to regenerate hyaline-like cartilage. Its use as an alternative to autologous chondrocyte implantation requires further investigation.

Collagen I membranes for tendon repair: Effect of collagen fiber orientation on cell behavior

Tendons have poor spontaneous regenerative capabilities, and complete regeneration is never achieved despite intensive remodeling. In this in vitro study, we characterized two multilamellar collagen I membranes differing in the arrangement of collagen fiber deposition (oriented vs. nonoriented) and compared their mechanical properties. Human dermal fibroblasts and tenocytes were seeded on the two membranes to evaluate the effect of fiber orientation on cell viability and cytoskeletal organization. Results demonstrate that the multilamellar collagen I membrane with oriented fibers has the better mechanical properties and affords optimum cell proliferation and adhesion. Its fiber arrangement provides an instructive pattern for cell growth and may serve to guide the alignment of cells migrating from the ends of a crushed or frayed tendon to obtain a strong, correctly structured tendon, thus providing a viable clinical option for tendon repair.

Oral chondroprotection with nutraceuticals made of chondroitin sulphate plus glucosamine sulphate in osteoarthritis.

Oral supplementation of chondroitin sulphate plus glucosamine helps repair the articular surface in osteoarthritis. Chondroitin-S reduces the concentration of the pro-inflammatory cytokines and transcription factor involved in inflammation. GlcN.S enhances cartilage specific matrix components and prevents collagen degeneration in chondrocytes by inhibiting hydrolytic enzymes, and preventing the oxidation of lipids and proteins. Chondroitin-S plus GlcN.S are slow-acting drugs that alleviate pain and partly restore joint function in OA patients. Orally administered pharmaceutical-grade chondroitin-S plus GlcN.S stabilize the joint space narrowing and significantly decrease the number of patients with new erosive OA. They are safe and no adverse events have ever been reported; they are recommended by EULAR and OARSI. The cost/effectiveness of the oral chondroitin-S plus GlcN.S therapy derives from the reduction of costs for physiotherapy, and for gastroprotective and non-steroidal drugs. The synergistic association of these two world-widely preferred nutraceuticals is a step forward in the management of OA.

Matrix-induced autologous chondrocyte implantation (MACI) in the knee

PurposeMatrix-induced autologous chondrocyte implantation (MACI) has been in use for chondral defect repair since 2000, but to date, only little is known about its histological outcomes in the repair of knee cartilage defects. This prospective multicentre study aims to evaluate (1) the quality of the repair tissue obtained from biopsies taken during second-look arthroscopy and (2) the relationship between the histological outcome, the macroscopic appearance of the repair and the patients’ functional status.MethodsThirty-three second-look core biopsies from 30 patients treated with MACI were analysed. At the time of biopsy, the surgeon reported the reason for the second-look arthroscopy, the quality of the repair tissue and the patient’s functional status on a standardised form. Biopsies together with patient data were sent to our centre to undergo blind histological evaluation and data analysis.ResultsThe median overall ICRS II histological score of the examined population was 57 (1st–3rd quartile 41–75). According to the ICRS cartilage repair assessment (CRA) arthroscopic evaluation, 10 biopsies (30%) were classified as normal, 17 (51%) as nearly normal, 4 (12%) as abnormal and 2 (6%) as severely abnormal. The histological outcome was not significantly related either to the macroscopic appearance of the lesion or to the patient’s functional status at the time of biopsy.ConclusionsIn the examined population, the macroscopic appearance of the repair tissue gave an overly favourable impression in comparison with the real histological composition of the tissue, which was possibly still maturing in many cases. The healing process after MACI needs to be better understood through a larger histological study, and a longer follow-up is needed to better clarify the relationship between histology and long-term functional status.Level of evidence IV.

Purified collagen I oriented membrane for tendon repair: an ex vivo morphological study.

Injured tendons have limited repair ability after full‐thickness lesions. Tendon regeneration properties and adverse reactions were assessed ex vivo in an experimental animal model using a new collagen I membrane. The multilamellar membrane obtained from purified equine Achilles tendon is characterized by oriented collagen I fibers and has been shown to sustain cell growth and orientation in vitro. The central third of the patellar tendon (PT) of 10 New Zealand White rabbits was sectioned and grafted with the collagen membrane; the contralateral PT was cut longitudinally (sham‐operated controls). Animals were euthanized 1 or 6 months after surgery, and tendons were subjected to histological and Synchrotron Radiation‐based Computed Microtomography (SRµCT) examination and 3D structure analysis. Histological and SRµCT findings showed satisfactory graft integration with native tendon. Histological examination also showed ongoing angiogenesis. Adverse side‐effects (inflammation, rejection, calcification) were not observed. The multilamellar collagen I membrane can be considered as an effective tool for tendon defect repair and tendon augmentation.

Arthroscopic management of heterotopic ossification of the subscapularis tendon in a patient with tuberculosis: a case report

Thepatient,a32-year-oldBangladeshimanwhohadworkedin Italy for many years, first came to the Orthopaedic ClinicShoulderUnitinMarch2009fordeep,anterior,sporadicpainin his left shoulder. He could recall no high- or low-energytraumas involving the shoulder or swelling of its anterioraspect. The pain was not related to his occupation. It pre-ventedhimfromsleepingpronewithhisarmunderthepillow(flexion and adduction of the glenohumeral joint).The patient was being treated at the Infectious DiseasesDepartment of our university hospital for TB, contracted inhis homeland. When he came to our attention, he wasreceiving maintenance therapy.

Gorham-Stout disease as a complication of posterior shoulder capsulorrhaphy

Gorham-Stout syndrome (GSS) is a rare condition characterized by rapid onset and massive osteolysis. It can affect any part of the skeleton and is most often seen in children and young adults of either sex; its etiology is unknown. We report a patient in whom GSS developed as a complication of arthroscopically treated posterior shoulder dislocation, review all possible factors to assess whether it was a direct consequence of the procedure or a long-term complication of the dislocation, and discuss the literature.

Basic Science and Injury in Growing Athletes: Muscle, Tendon, and Ligament

Physical activity and sports nowadays constitute one of the foundations for a correct psychophysical development, both in children and adolescents. It has been accounted that about 30 million children across the United States participate in organized athletic activities, and this number is increasing; the same increasing trend has been recently reported in Europe by the Olympic Committees. Even though, on the one hand, these activities lead to lifelong habits of exercising and teamwork value, on the other hand, as the competition and the technical complexity of exercises increases, training, and workout become longer and more intense with shorter rest periods. The accumulation of repetitive stress without adequate recovery time along with skeletal immaturity can cause many soft tissue injuries. In particular, sports injuries are responsible for nearly a quarter of all injuries in children and adolescents. The aim of this chapter is to provide a report on epidemiology, risk factors and basic science in soft tissue injuries (muscles, tendons, and ligaments), from trauma to recovery, involving the young “growing” athlete.