Dermal substitutes bear a high clinical demand because of their ability to promote the healing process of cutaneous wounds by reducing the healing time the appearance and improving the functionality of the repaired tissue. Despite the increasing development of dermal substitutes, most of them are only composed of biological or biosynthetic matrices. This demonstrates the need for new developments focused on using scaffolds with cells (tissue construct) that promote the production of factors for biological signaling, wound coverage, and general support of the tissue repair process. Here, we fabricate by electrospinning two scaffolds: poly(ε-caprolactone) (PCL) as a control and poly(ε-caprolactone)/collagen type I (PCol) in a ratio lower collagen than previously reported, 19:1, respectively. Then, characterize their physicochemical and mechanical properties. As we bear in mind the creation of a biologically functional construct, we characterize and assess in vitro the implications of seeding human Wharton's jelly mesenchymal stromal cells (hWJ-MSCs) on both scaffolds. Finally, to determine the potential functionality of the constructs in vivo, their efficiency was evaluated in a porcine biomodel. Our findings demonstrated that collagen incorporation in the scaffolds produces fibers with similar diameters to those in the human native extracellular matrix, increases wettability, and enhances the presence of nitrogen on the scaffold surface, improving cell adhesion and proliferation. These synthetic scaffolds improved the secretion of factors by hWJ-MSCs involved in skin repair processes such as b-FGF and Angiopoietin I and induced its differentiation towards epithelial lineage, as shown by the increased expression of Involucrin and JUP. In vivo experiments confirmed that lesions treated with the PCol/hWJ-MSCs constructs might reproduce a morphological organization that seems relatively equivalent to normal skin. These results suggest that the PCol/hWJ-MSCs construct is a promising alternative for skin lesions repair in the clinic.
The challenge of bone tissue regeneration implies the use of new advanced technologies for the manufacture of polymeric matrices, with 3D printing technology being a suitable option for tissue engineering due to its low processing cost, its simple operation and the wide use of biomaterials in biomedicine. Among the biopolymers used to obtain porous scaffolds, poly(lactic acid) (PLA) stands out due its mechanical and biodegradability properties, although its low bioactivity to promote bone regeneration is a great challenge. In this research, a 3D scaffold based on PLA reinforced with bioceramics such as graphene oxide (GO) and β-tricalcium phosphate (TCP) was designed and characterized by FTIR, XRD, DSC, SEM and mechanical tests. The in vitro biocompatibility, viability, and cell proliferation of the poly-L-lysine (POLYL) functionalized scaffold were investigated using Wharton Jelly mesenchymal stem cells (hWJ-MSCs) and confirmed by XPS. The incorporation of GO/TCP bioceramics into the PLA polymer matrix increased the mechanical strength and provided a thermal barrier during the fusion treatments that the polymeric material undergoes during its manufacturing. The results show that the functionalization of the scaffold with POLYL allows improving the cell adhesion, proliferation and differentiation of hWJ-MSCs. The resulting scaffold PLA/GO/TCP/POLYL exhibits enhanced structural integrity and osteogenic cues, rendering it a promising candidate for biomedical applications.
Bone repair via endochondral ossification is a complex process for the critical size reparation of bone defects. Tissue engineering strategies are being developed as alternative treatments to autografts or allografts. Most approaches to bone regeneration involve the use of calcium composites. However, exploring calcium-free alternatives in endochondral bone repair has emerged as a promising way to contribute to bone healing. By analyzing researches from the last ten years, this review identifies the potential benefits of such alternatives compared to traditional calcium-based approaches. Understanding the impact of calcium-free alternatives on endochondral bone repair can have profound implications for orthopedic and regenerative medicine. This review evaluates the efficacy of calcium-free alternatives in endochondral bone repair through in vivo trials. The findings may guide future research to develop innovative strategies to improve endochondral bone repair without relying on calcium. Exploring alternative approaches may lead to the discovery of novel therapies that improve bone healing outcomes.
Chronic cutaneous ulcers pose a major clinical challenge due to persistent inflammation, impaired angiogenesis, and limited regenerative capacity, underscoring the need to develop bioactive scaffolds that mimic the extracellular matrix (ECM) and promote skin repair. In this study, electrospun Poly(ε-caprolactone) (PCL) scaffolds functionalized with 10% (PCLGLI10) and 20% (PCLGLI20) glycine were fabricated, physicochemically and mechanically characterized, and evaluated in combination with human Wharton’s jelly mesenchymal stromal cells (hWJ-MSCs). Glycine incorporation reduced fiber diameter to the nanoscale range (140–155 nm) and increased scaffold porosity (~71–72%) while preserving mechanical properties compatible with skin. FTIR and X-ray diffraction analyses confirmed glycine incorporation and a polymorphic transition from α- to γ-glycine during electrospinning. Cell viability remained above 95% in all scaffolds; however, PCLGLI10 significantly enhanced cell proliferation, metabolic activity, and the secretion of VEGF and HGF, mediators associated with angiogenesis and tissue repair. Furthermore, in a guinea pig full-thickness wound model, the PCLGLI10+hWJ-MSCs construct promoted a modulated inflammatory response and more organized collagen deposition. These findings support the potential of glycine-functionalized electrospun scaffolds as a promising strategy for chronic cutaneous ulcer regeneration.