Biodegradation, biocompatibility, and osteoconduction evaluation of collagen‐nanohydroxyapatite cryogels for bone tissue regeneration

Abstract

Designing biomimetic biomaterials inspired by the natural complex structure of bone and other hard tissues is still a challenge nowadays. The control of the biomineralization process onto biomaterials should be evaluated before clinical application. Aiming at bone regeneration applications, this work evaluated the in vitro biodegradation and interaction between human bone marrow stromal cells (HBMSC) cultured on different collagen/nanohydroxyapatite cryogels. Cell proliferation, differentiation, morphology, and metabolic activity were assessed through different protocols. All the biocomposite materials allowed physiologic apatite deposition after incubation in simulated body fluid and the cryogel with the highest nanoHA content showed to have the highest mechanical strength (DMA). The study clearly showed that the highest concentration of nanoHA granules on the cryogels were able to support cell type's survival, proliferation, and individual functionality in a monoculture system, for 21 days. In fact, the biocomposites were also able to differentiate HBMSCs into osteoblastic phenotype. The composites behavior was also assessed in vivo through subcutaneous and bone implantation in rats to evaluate its tissue-forming ability and degradation rate. The cryogels Coll/nanoHA (30 : 70) promoted tissue regeneration and adverse reactions were not observed on subcutaneous and bone implants. The results achieved suggest that scaffolds of Coll/nanoHA (30 : 70) should be considered promising implants for bone defects that present a grotto like appearance with a relatively small access but a wider hollow inside. This material could adjust to small dimensions and when entering into the defect, it could expand inside and remain in close contact with the defect walls, thus ensuring adequate osteoconductivity.

Composite Cryogel with Polyelectrolyte Complexes for Growth Factor Delivery

“…Therefore, to reinforce the strength of the cryogel for compression or other types of stress and to increase biocompatibility and accelerate biomineralization of the cryogel, HA was introduced. Mechanical measurements showed that addition of HA significantly increased the elastic modulus of CHI-PVA-HA-Hep-GA cryogel (1085 ± 428 kPa) and that the value was significantly higher in comparison to other cryogel-based scaffolds designed for bone regeneration [43][44][45][46][47][48][49]. Degradation experiments confirmed a decreased in vitro degradation rate of HA-containing cryogels, which is in line with other published data [45,50].…”

Biomedical Applications of Polymeric Cryogels

“…In vitro: Differentiation of human bone marrow stromal cells into osteoblastic phenotype. In vivo: Reduced inflammatory response by new tissue production [72] Collagen-nanoHA biocomposite cryogels…”

Potential Therapeutic Applications of Exosomes in Bone Regenerative Medicine

“…Normal bone regeneration is a complex but well-orchestrated physiological process that includes the initiation of ossification, osteoinduction, and osteogenesis [6][7][8][9]. Specifically, when bone injury occurs, a series of signaling pathways is activated, which, in turn, leads to angiogenesis and other downstream events, and these together establish a favorable microenvironment, which set the stage for stem cell based fracture healing/regeneration [10].…”