The 13th International BMP Conference was held in October 2022 in Dubrovnik. The conference was attended by more than 240 participants from North America, Europe, Asia, and Australia who got an ...insight into the latest achievements in basic, translational, and clinical research of BMP mol- ecules through 75 lectures categorized into several scientific sections. This review paper provides the most important novel findings on the structure, function, and signaling of BMPs, the role of BMPs in patterning and organoids as well as the role of BMP in metabolism. Moreover, we discussed
the role of BMPs in various diseases including cancer pathogenesis, pulmonary arterial hyperten- sion, and fibrodysplasia ossificans progressiva (FOP). Finally, we provided an overview of the new BMP-based therapies in regenerative medicine that are currently in different stages of preclinical and clinical trials.
Koštani morfogenetski proteini (BMP) čine grupu čimbenika rasta i diferencijacije unutar TGFβ nado- bitelji. Oni induciraju stvaranje ektopične i ortotopične endohondralne kosti te su uključeni u ...regulaciju stanične proliferacije, diferencijacije, apoptoze i mezenhimalno-epitelne interakcije u važnim tkivnim morfogenetskim procesima izvan koštanog sustava. Koštane naprave koje sadrže BMP2 i BMP7 pro- tein odobrene su za poboljšanje koštanog cijeljenja kod pacijenata s defektima dugih cjevastih kostiju i kod prednje spinalne fuzije kralježnice. Međutim, zbog visoke cijene i mnogobrojnih nuspojava koje su uključivale pojavu heterotopičnih osifikacija, retrogradnu ejakulaciju i bol, njihova je klinička prim-
jena ograničena. U ovom smo preglednom radu raspravili otkriće BMP molekula, njihovu biologiju i primjenu u kliničkim studijama s posebnim osvrtom na nedavno otkrivenu novu autolognu koštanu napravu (ABGS) koja sadrži BMP6. Novi ABGS sastoji se od nosača autolognog koaguluma (ABC) s otopljenim BMP6 koji je ključan za pokretanje diferencijacije mezenhimalnih stanica u smjeru stvaranja endohondralne kosti. ABC je ispunio sve potrebne uvjete za formulaciju optimalnog nosača za BMP6 isključivo zbog jednostavnosti priprave i primjene te odsustva imunogenog i upalnog odgovora na mjestu implantacije. Uz dodatak alografta ili sintetičke keramike što je potvrđeno na životinjskim modelima došlo je do značajnog povećanja volumena te poboljšanja mikroarhitekture novonastale kosti. Prvo kliničko ispitivanje provedeno je na pacijentima s distalnim prijelomima radijusa (faza I studije), a drugo na pacijentima koji su podvrgnuti visokoj osteotomiji tibije (faza I/II studije) bez uočenih ozbiljnih nuspojava. Trenutno je u tijeku studija OSTEOproSPINE u kojoj se testira učinkovitost ABGS u kom- binaciji s koštanim alograftom u bolesnika s kroničnim bolovima u leđima uzrokovanim degenerativnim promjenama intervertebralnog diska. Nova ABGS koštana naprava značajna je prekretnica i napredak u području koštane biologije te regenerativne medicine koštanog sustava.
The treatment of cartilage defect remains a challenging issue in clinical practice. Chitosan-based materials have been recognized as a suitable microenvironment for chondrocyte adhesion, ...proliferation and differentiation forming articular cartilage. The use of nasal chondrocytes to culture articular cartilage on an appropriate scaffold emerged as a promising novel strategy for cartilage regeneration. Beside excellent properties, chitosan lacks in biological activity, such as RGD-sequences. In this work, we have prepared pure and protein-modified chitosan scaffolds of different deacetylation degree and molecular weight as platforms for the culture of sheep nasal chondrocytes. Fibronectin (FN) was chosen as an adhesive protein for the improvement of chitosan bioactivity. Prepared scaffolds were characterised in terms of microstructure, physical and biodegradation properties, while FN interactions with different chitosans were investigated through adsorption–desorption studies. The results indicated faster enzymatic degradation of chitosan scaffolds with lower deacetylation degree, while better FN interactions with material were achieved on chitosan with higher number of amine groups. Histological and immunohistochemical analysis of
in vitro
engineered cartilage grafts showed presence of hyaline cartilage produced by nasal chondrocytes.
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