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A multilayered polylactic acid (PLA)/halloysite (HAL) porous membrane encapsulated with aminoglycoside antibiotic (gentamicin) was prepared by electrospinning technique. The prepared electrospun membrane displayed smooth morphology and uniform fiber distribution, while various layers of PLA mats were tightly bounded together. Significant enhancement in mechanical properties and stability was observed in membranes reinforced by HAL and the multilayered membrane loaded with gentamicin, while the drug loaded membrane showed no delamination. In addition, incorporation of HAL led to improvement in thermal stability of the PLA nanofibrous membranes. The in vitro drug release study of gentamicin loaded membrane initially shows a burst release of gentamicin, followed by slow rate of drug release up to 48 h. Antimicrobial efficacy of electrospun membrane was tested on a gram-positive (Staphylococcus aureus) and a gram-negative (Escherichia coli) bacteria, while results indicated that the gentamicin released from electrospun membrane has retained its antibacterial activity. These results signified the potential of multilayered porous PLA/HAL membranes to be utilized in prevention of infection in bone regeneration applications.

Despite the promise of hydrogel-based stem cell therapies in orthopedics, a significant need still exists for the development of injectable microenvironments capable of utilizing the regenerative potential of donor cells. Indeed, the quest for biomaterials that can direct stem cells into bone without the need of external factors has been the "Holy Grail" in orthopedic stem cell therapy for decades. To address this challenge, we have utilized a combinatorial approach to screen over 63 nanoengineered hydrogels made from alginate, hyaluronic acid, and two-dimensional nanoclays. Out of these combinations, we have identified a biomaterial that can promote osteogenesis in the absence of well-established differentiation factors such as bone morphogenetic protein 2 (BMP2) or dexamethasone. Notably, in our "hit" formulations we observed a 36-fold increase in alkaline phosphate (ALP) activity and a 11-fold increase in the formation of mineralized matrix, compared to the control hydrogel. This induced osteogenesis was further supported by X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, and energy-dispersive X-ray spectroscopy. Additionally, the Montmorillonite-reinforced hydrogels exhibited high osteointegration as evident from the relatively stronger adhesion to the bone explants as compared to the control. Overall, our results demonstrate the capability of combinatorial and nanoengineered biomaterials to induce bone regeneration through osteoinduction of stem cells in a natural and differentiation-factor-free environment.