Osteochondral defects are a particular kind of cartilage damage involving cartilage and underlining subchondral bone. Osteochondral defects have a restricted potential to heal spontaneously, primarily as a result of avascular nature of cartilage and disrupted subchondral bone perform [1]. In recent times, tissue-engineered osteochondral implants that mix cells, hydrogels, scaffolds, and bioactive molecules have grow to be a possible therapy technique [2], [3].
From the angle of biomimicry, a perfect osteochondral implant ought to have an acceptable biochemical microenvironment for tissue regeneration and possess enough mechanical energy to imitate native osteochondral tissue [4], [5]. Hydrogels, reminiscent of gelatin methacryloyl (GelMA), alginate, and polyethylene glycol diacrylate (PEGDA), when used alone for osteochondral restore, typically lack the mandatory mechanical energy to assist the weight-bearing features of cartilage and bone [6], [7]. 3D printed polyester scaffolds, together with these created from polycaprolactone (PCL), polylactic acid (PLA), and poly(lactide-co-glycolide) (PLGA), present the required mechanical assist and nutrient change however could not sufficiently replicate the smooth and hydrated nature of cartilage [8], [9]. The rigidity of pure polyester constructs can even impede cell attachment and proliferation, that are important for profitable tissue regeneration [10].
Hybrid method combines the mechanical assist of 3D printed polyester scaffolds with the biocompatible and hydrated microenvironment of hydrogels. Nevertheless, the combination of a polyester-based osteochondral implant inside an optimized organic microenvironment poses a number of challenges, specifically the creation of a multi-stage porous structure, exact anatomical form replication and, crucially, the replication of mechanical properties that match native osteochondral tissue. Incorporating bioactive molecules into hydrogels can enhance their organic properties. Optimizing the hierarchical construction of scaffolds can improve tissue formation and mechanical properties, and forming a hybrid assemble laden with cells optimum for chondrogenesis can improve cartilage regeneration [11], [12], [13], [14]. Mesenchymal stem cells (MSCs) are a promising cell supply for cartilage tissue engineering owing to their self-renewal and chondrogenic differentiation potential. Our earlier work demonstrated that, in contrast with bone marrow MSCs (BMMSCs), peripheral blood MSCs (PBMSCs) may higher adapt to the oxygen-deficient setting (i.e., ischemic articular cartilage) [15], and possess stronger chondrogenic potential [16]. The power of PBMSCs to enhance osteochondral-defect restore was additionally demonstrated in a rabbit mannequin and clinically in taekwondo athletes [17], [18].
This research aimed to mix the benefits of sturdy PLGA scaffolds and bioactive thermosensitive hydrogels for higher structural and purposeful mimicry of osteochondral tissues. We designed an osteochondral hybrid implant with multistage porous structure, enough mechanical energy, and osteoinductive and chondroinductive talents (Fig. 1). This design was primarily based on a three-dimensional (3D)-printed PLGA scaffold ornamented with a poly(ethylene glycol)2k-block-poly(γ-ethyl-l-glutamate)m (PEG2k-b-PELGm) thermosensitive hydrogel, as described beforehand [19]. PLGA scaffolds with controllable porous structure and tunable mechanical energy have been fabricated utilizing low-temperature deposition modeling (LDM) and the salt-leaching methodology. PEG2k-b-PELGm thermogels have been functionalized with the adhesive peptide Arg-Gly-Asp (RGD) to reinforce cell proliferation and small chondrogenic molecule kartogenin (KGN) to enhance the chondrogenic capability. Furthermore, we demonstrated that high-quality osteochondral restore was achieved after the PBMSC-loaded hybrid scaffold was implanted into the osteochondral defect of the rabbit femoral trochlear.
